CA2307320A1 - 148 human secreted proteins - Google Patents
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- CA2307320A1 CA2307320A1 CA002307320A CA2307320A CA2307320A1 CA 2307320 A1 CA2307320 A1 CA 2307320A1 CA 002307320 A CA002307320 A CA 002307320A CA 2307320 A CA2307320 A CA 2307320A CA 2307320 A1 CA2307320 A1 CA 2307320A1
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Abstract
The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.
Description
DE3IIlANDES OU BREVETS VOLUMINEUX
LA PRESENTS PARTIE DE CETTE DEMANDS OU CE BREVET
CECi EST LE TOME ~ DE
NOTE. Pour les tomes additionels, veuillez contacter to Bureau canadien des brevets JUMBO APPLlCATIONS/PATENTS .
THIS SECTION OF THE APPUCATIONIPATENT CONTAINS MORE
'THAN ONE VOLUME
THIS IS VOLUME ~_ OF
' NOTE: For additional volumes-phase contact the Canadian Patent Office .
148 Human Secreted Proteins Field of the Invention This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides, uses of such polynucleotides and polypeptides, and their production.
Background of the Invention Unlike bacterium, which exist as a single compartment surrounded by a membrane, human cells and other eucaryotes are subdivided by membranes into many functionally distinct compartments. Each membrane-bounded compartment, or organelle, contains different proteins essential for the function of the organelle. The cell uses "sorting signals," which are amino acid motifs located within the protein, to target proteins to particular cellular organelles.
One type of sorting signal, called a signal sequence, a signal peptide, or a leader sequence, directs a class of proteins to an organelle called the endoplasmic reticulum (ER). The ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles.
Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space - a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a "linker" holding the protein to the membrane.
Despite the great progress made in recent years, only a small number of genes encoding human secreted proteins have been identified. These secreted proteins include the commercially valuable human insulin, interferon, Factor VIII, human growth hormone, tissue plasminogen activator, and erythropoeitin. Thus, in light of the pervasive role of secreted proteins in human physiology, a need exists for identifying and characterizing novel human secreted proteins and the genes that encode them. This knowledge will allow one to detect, to treat, and to prevent medical disorders by using secreted proteins or the genes that encode them.
Summary of the Invention The present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides.
Also provided are diagnostic methods for detecting disorders related to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides.
Detailed Description Definitions The following definitions are provided to facilitate understanding of certain terms used throughout this specification.
In the present invention, "isolated" refers to material removed from its original environment {e.g., the natural environment if it is naturally occurring), and thus is altered "by the hand of man" from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be "isolated" because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide.
In the present invention, a "secreted" protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a "mature" protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.
As used herein , a "polynucleotide" refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5' and 3' untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence.
Moreover, as used herein, a "polypeptide" refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined.
In the present invention, the full length sequence identified as SEQ ID NO:X
was often generated by overlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID
NO:X was deposited with the American Type Culture Collection ("ATCC"). As shown in Table 1, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Virginia 20110-2209, USA. The ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure.
A "polynucleotide" of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the cDNA within the clone deposited with the ATCC. "Stringent hybridization conditions" refers to an overnight incubation at 42°
C in a solution comprising 50% formamide, Sx SSC {750 mM NaCI, 75 mM sodium citrate), 50 mM sodium phosphate (pH 7.6)> Sx Denhardt's solution, 10% dextran sulfate, and 20 ~tg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in O.Ix SSC at about 65°C.
Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions.
Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature.
For example, lower stringency conditions include an overnight incubation at 37°C in a solution comprising 6X SSPE (20X SSPE = 3M NaCI; 0.2M NaH~PO~; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide> 100 ug/ml salmon sperm blocking DNA;
followed by washes at 50°C with 1XSSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. SX SSC).
Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide," since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone}.
The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA
or modified RNA or DNA. For example, polynucleotides can be composed of single-and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single-and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA
and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms.
The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art.
Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched , for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods.
Modifications include acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI
anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins 5 such as arginylation, and ubiquitination. (See, for instance, PROTEINS -STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W.
H. Freeman and Company, New York ( 1993); POSTTRANSLATIO.NAL
COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. I-I2 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990);
Rattan et al., Ann NY Acad Sci 663:48-62 ( 1992).) "SEQ ID NO:X" refers to a polynucleotide sequence while "SEQ ID NO:Y"
refers to a polypeptide sequence, both sequences identified by an integer specified in Table I.
"A polypeptide having biological activity" refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.) Polynucleotides and Polxpeptides of the Invention FEATURES OF PROTEIN ENCODED BY GENE NO: 1 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
MRFISQQSCECVRPCMDVYVCVYISIHVYMDAHVYLCRICKTNMR (SEQ >D
N0:309), RILRWVNCMACDLYLNKAVSVCAHVWMCMCVYISLYMYTWMP
MCIYVEYVKQT (SEQ ID N0:310), NPENQLEISFPPRRQKMKLTLDLQVSQS
SLVHSLLSSDFFSVSKEGCLWKPILLPSHFL (SEQ ID N0:311), LQTQISN
YLMFVLHILHRYTWASMYTCIEIYTHTYTSIHGRTHSQLC (SEQ ID N0:312), IHMGIHVYMYRDIYTHIHIHTWAHTLTALLRYKSHAIQLTHLNIR (SEQ ID
N0:313), and/or MKWIFTVLILTSCFFTAGICEDGICSRIQL RDKIVQSAFRQ (SEQ
ID N0:314). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, particularly neutropenia and related conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoeitic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders. More specifically, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:11 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 812 of SEQ ID NO:11, b is an integer of 15 to 826, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:11, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 2 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
KPCCPSVSNRSSVQMHQLPIQFLGQFEAHCIGFCRSFLETFYTHDPRAMHSFL
SSISSPSLPFGFSRMTSQINHLHPSPLC (SEQ ID N0:315). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, particularly neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune. hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:161 as residues: Asp-15 to Tyr-21, Pro-29 to Asn-39.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders.
Moreover, the expression of this gene product indicates a role in the regulation of the proliferation;
survival; differentiation; and/or activation of hernatopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:12 and may have been publicly available prior to conception of the present invention. Preferably, such related polynueleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 510 of SEQ ID N0:12, b is an integer of 15 to 524, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:12, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 3 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: SVFKINLKSFKQHEPWWPNRS (SEQ ID N0:316).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, including neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:162 as residues: Met-I to Arg-8, Leu-35 to Glu-41.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders. More specifically, expression of this gene product indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may also be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease. inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
WO 99122243 PCT/US9$122376 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:13 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the 5 scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 477 of SEQ ID N0:13, b is an integer of 15 to 491, where both a and b correspond to the positions of nucleotide residues shown in 10 SEQ ID N0:13, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 4 This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune disorders, including neutrophenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:163 as residues: Asn-45 to Thr-58.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment andlor prevention of a variety of immune disorders. In particular, this gene product may play a role in regulating the proliferation; survival; differentiation; andlor activation of hematopoietic cell lineages, including blood stem cells. Furthermore, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, IO rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
I5 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:14 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
20 Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 389 of SEQ ID N0:14, b is an integer of 15 to 403, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:14, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 5 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GTRSFSVPSYLRLTGSLMCYLLLLLIQTAELLIHPQGLQAVSNGESALKGTRPTF
SSPFILVTEGRKEWEGVFLSSGWKGNTLSNYYISLVFYYSRILQPYFYCLWGK
LEMVTLIRSVWRGINGGDKISVGFGKC (SEQ ID N0:317), WMERKHTVKLL
YLLGFLLQNSPAIFLLSMGEVGDGDLD (SEQ ID N0:318) SNGESALKGTRP
TFSSPFILVTE (SEQ ID N0:319), and/or LSNYYISLVFYYSRILQPYFYCLW (SEQ
ID N0:320). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.
This gene is expressed primarily in the breast and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, reproductive, or neural disorders, such as cancers of the breast, lymph system and brain. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive, immune, and central nervous systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, neural, breast, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:164 as residues: Leu-31 to Phe-38, Glu--47 to Trp-52.
The tissue distribution in breast and brain tissue indicates that polynucleotides and polypeptides cowesponding to this gene are useful for the diagnosis and treatment of cancers in the breast, lymph system, and brain. Moreover, the protein product of this gene may be useful for the detectionltreatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:15 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 799 of SEQ ID NO:15, b is an integer of I S to 813, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:15, and where b is greater than or equal to a + I4.
FEATURES OF PROTEIN ENCODED BY GENE NO: 6 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:165 as residues: Ser-49 to Leu-54.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune disorders. Moreover, the expression of this gene product indicates a role in regulating the proliferation; survival;
differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lease tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:16 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 250 of SEQ ID N0:16, b is an integer of 1 ~ to 264, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:16, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 7 The translation product of this gene shares sequence homology with neurotoxin which is thought to be important in neural diseases. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
EKDFMQGSDAGHGGTHIYRALVQWPLAWVFYLSHAKTHWGEELRFSFRRKN
LRLREAMRHETCQVTQLVA GKADSNLCLRDSETWFWPPLWAACSSLQATA
CRLSSPSKGLGASRECPWLASGRAALVSFL (SEQ ID N0:321), SLRVKGRKPR
LLYHSPARGTLWMLPGLCDCL ICRQWLVERSRLPRVGARTRFQSP SDTGWS
QLCQLPAV (SEQ ID N0:322), and/or ERSRLPRVGARTRFQSPSDTGWSQLC
(SEQ ID N0:323). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and neural diseases, particularly neurodegenerative disorders, such as Alzheimers or Parkinson's. Similarly, polypeptides and antibodies directed to 10 these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hemaopoietic, neural, and cancerous and wounded tissues) or bodily 15 fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:166 as residues: Gln-2 to Gly-10, Asp-77 to Phe-82.
The tissue distribution in neutrophils combined with the homology to the conserved neurotoxin protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune and neural diseases.
Similarly, the protein product of this gene may be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders. or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular WO 99r12243 PCT/US98/22376 system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:17 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 506 of SEQ ID NO: I7, b is an integer of 15 to 520, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: I7, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 8 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KHAFLMAHQFCVLSLAMQWSSCFQLVALPYLSL (SEQ ID
N0:324). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of immune disorders. Furthermore, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimrnune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease. scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:18 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 979 of SEQ ID N0:18. b is an integer of 15 to 993, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:18, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 9 When tested against Jurket and PC12 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) and (early growth response gene 1) promoter elements. Thus, it is likely that this gene activates T-cells and sensory neurons through the JAK-STAT and EGR1 signal transduction pathways. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
WO 99r12243 PCT/US98/22376 sy Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. EGR1 is a separate signal transduction pathway from Jak-STAT, genes containing the EGR 1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: MRPLCVLLPWPCWQWGGLGSASPIRPQAPPGQAAHAVP
LPRAQHLAQRSRQ (SEQ ID N0:325). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.
This gene is expressed primarily in breast, lymph nodes, spleen, and to a lesser extent, in liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, immune, or hepatic disorders, particularly cancers of the breast, liver. and lymph system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast, liver and lymph system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, breast, immune hematopoietic, hepatic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk. bile. serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder; relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:168 as residues: Pro-54 to Gly-57.
The tissue distribution in breast and immune tissues combined with the detected EGR 1 and GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancers of the breast and lymph systems. Moreover, the GAS and EGR 1 activity strongly indicates that the protein product of this gene may play an integral role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, such proliferative tissues rely on finely regulated decisions involving cell differentiation and/or apoptosis. Thus this protein may also be involved in regulating apoptosis or tissue differentiation and, thus could be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:19 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 445 of SEQ ID N0:19, b is an integer of 15 to 459, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:19, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 10 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARGLRSPHGAAGVVRGDGGGKKGEDPYSPILFQ
SERIPRLIYLPVISSEENS (SEQ ID N0:326). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in an LPS induced neutrophil cDNA library.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune system disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders, for example, in ameliorating an abberant neutrophil reponse to infectious agents. Similarly, the expression of this gene product may suggest a role in 5 regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may also be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene 10 product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia. neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to 15 transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed 20 progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:20 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded, from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 541 of SEQ ID N0:20, b is an integer of 15 to 555, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:20, and where b is greater than or equal to a + 14.
WO 99/22243 PCTIUS98I2237b FEATURES OF PROTEIN ENCODED BY GENE NO: 11 This gene is expressed primarily in prostate cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive or immune system disorders, particularly prostate cancer.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, prostate, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:170 as residues: Pro-14 to Asp-25, Leu-51 to V al-63.
The tissue distribution in prostate tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive system disorders such as cancer, particularly prostate cancer.
Similarly, the expression within prostate cancer tissue, a cellular source marked by proliferating cells, indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders not limited to prostate tissue. Further, such tis>ues rely on decisions involving cell differentiation and/or apoptosis. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 651 of SEQ ID N0:21, b is an integer of 15 to 665, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:21, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 12 The polynucleotide sequence of this gene may have a frame shift. Therefore the preferred signal peptide may reside in a frame other than the associated polynucleotides of this gene. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
KSLSCSFLFLAFWLRRMGQTMCVCVCVCVCVCVRTWVYLYEPVKF RSPLIYV
NLPTS (SEQ ID N0:327), and/or KLGFTMLARLVSNSXTSGDLPSSASQNAGI
KGMSYRAWPYSYFLIRKNKQT NKQTKTNPQLGENKHCRNLKVSWSKNYFL
(SEQ ID N0:328). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune system disorders, particularly immunodeficiencies such as lupus and AIDS, or inflammatory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Moreover, this gene product may play a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:22 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 763 of SEQ ID N0:22, b is an integer of 15 to 777, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:22, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 13 When tested against Jurket and U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element. Thus, it is likely that this gene activates T-cells and promyelocytic cells through the JAK-STAT signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT
pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
ERGQGGSSRNVAGSDLVFPAVFVSXLC (SEQ ID N0:329), GSPQGPS VALGSRQCWSRPLRRGGRGAAVEMWRGPTWCFRPSLCLCCVCGV
SFGLYVPHGFSLSMCVSAP GSAWLSLVYSICLARGSMSXRXSSRXSLV
ASGAS VLLVCFW VXADPG VG VS VPRAXVSGLWWCVSPSACLXLAPTKPPP
XLSFSLSIFPFSSNPSK (SEQ ID N0:330), and/or TIASLQPTALNHLIWRGW
KRKGRLRERKRGXGGAWLGPXRGRQMDSHTTRDQRQXLGEQRHPLLGLXA
PRSKPTKQMPQMQPGXPEKKXXLTWNHGLDRWNTQGTARQSLGQK
HTWRD (SEQ ID N0:331 ). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adipose tissue and the brain.
Therefore, polynucleotides arid polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, metabolic or neural disorders, particularly obesity, and neurodegenerative or central nervous system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes far differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.adipose, neural, immune, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in adipose and neural tissues, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of obesity and disorders of the brain and central nervous system. Similarly, the protein product of this gene may be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism. and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or 5 survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. In addition, the protein product of this gene may also be beneficial in detecting, treating, or preventing neural disorders which occur secondary to aberrant fatty acid metabolism in neural 10 tissues, such as for aberrations in myelin sheath development, or associated autoimmune disorders of neural tissue or the overlying integument. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available 15 and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:23 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more 20 polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 526 of SEQ ID N0:23, b is an integer of 15 to 540, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:23, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 14 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARGPGTEGCEPWLQLQDRRER (SEQ ID N0:332), and/or MSSGTNSFFTLMALNSPTGDSGSRITVSPPRVHPVKSGRGRASDLLLTRFLAPR
SALWS {SEQ ID N0:333). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in a cDNA library from IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune system disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of conditions where lymphocytes show abberant response to an infectious agent.
Similarly, this gene product may play a role in regulating the proliferation;
survival;
differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:24 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 470 of SEQ ID N0:24, b is an integer of 15 to 4$4, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:24, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 15 This gene is expressed primarily in ovaries, tonsils, and CD34 positive bone marrow stem cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, immune, developmental, or hematopoietic disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, ovarian, immune, tonsil, umbilical, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in ovarian and tonsil tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune and reproductive system disorders. Similarly, expression of this gene product in tonsils indicates a role in regulating the proliferation; survival;
differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, WO 99!22243 PCT/US98/22376 neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, S rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:25 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 693 of SEQ ID N0:25, b is an integer of 15 to 707, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:25, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 16 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocyctic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: HEYHLLSSRHILGSVLRLDVC SALWS (SEQ ID N0:334).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune. hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells combined with the detected GAS
biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, andlor prevention of immune disorders.
Specifically, the expression of this gene product in neutrophils indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity: immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:26 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 779 of SEQ ID N0:26, b is an integer of 15 to 5 793, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:26, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 17 This gene is expressed primarily in the spinal cord.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, any of a variety of nervous system and neuromuscular disorders, particularly amyotropic lateral sclerosis, musculuar dystrophy, and inherited and non-inherited forms of chorea. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system and neuromuscular systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, neuromuscular, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spinal cord tissue indicates that this gene could be used for the treatment of spinal cord and related injuries. The protein product of this gene could be injected into the spinal cord to promote or control growth following injuring or degeneration. Alternatively cells expressing this gene could be injected or transferred into the spinal cord by other means as a treatment promoting the regulation of growth following spinal cord injury or degeneration. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease> Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:27 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 624 of SEQ ID N0:27, b is an integer of 15 to 638, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:27, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: Z8 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS {gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
FILFILEYDMLWKSLYTNSSAYGYVIASYFCLLGIKLLVKQKKXKKKTRGGAR
X PIRPXVESYYKSXAVVLQRRGLGKNLGG (SEQ ID N0:335). Poiynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in the adrenal gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine disorders, particularly disorders of the adrenal gland.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the adrenal gland. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endocrine, adrenal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a 1 S disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in adrenal tissue, combined with the detected GAS
biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many poiynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:28 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 514 of SEQ ID N0:28, b is an integer of 15 to 528, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:28, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 19 This gene is expressed primarily in the placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types {e.g.placental, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:178 as residues: His-15 to Trp-20, Pro-48 to Ala-54.
The tissue distribution in placental tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of reproductive disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:29 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 905 of SEQ ID N0:29, b is an integer of 15 to 919, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:29, and where b is greater than or equal to a + 14.
WO 99/22243 PCT/US98/223~6 FEATURES OF PROTEIN ENCODED BY GENE NO: 20 The translation product of this gene shares sequence homology with human erythrocyte membrane anion-transport protein which is thought to be important in autoimmune diseases. Furthermore, the translation product of this gene also has homology to a human gnlIPIDId1026838 (AB012130) sodium bicarbonate cotransporter2 which is.thought to be important in maintaining cellular homoestasis.
Contact of cells with supernatant expressing the product of this gene was found to increase the permeability of the plasma membrane of enterocytes and renal mesangial cells to calcium. Thus it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product binds a receptor on the surface of the enterocytes and renal mesangial cells. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating cellular processes within enterocytes and renal mesangial cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
RVSSHLFRLFGGLILDIKRKAPFFLSDFKDALSLQCLASILFLYCACMSPVITFG
GLLGEATEG RIVSTKIGSGQAFSSSEASVCMHLSHYSYFYLKSLPTA (SEQ ID
N0:336), FRLFGGLILDIKRKAPFFLSDFKD {SEQ ID N0:337), FLYCACMSPV
ITFGGLLGEATEG (SEQ ID N0:338), andlor SSSEASVCMHLSHYSYFYLKSL
(SEQ ID N0:339). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3.
This gene is expressed primarily in human testes tumor.
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148 Human Secreted Proteins Field of the Invention This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides, uses of such polynucleotides and polypeptides, and their production.
Background of the Invention Unlike bacterium, which exist as a single compartment surrounded by a membrane, human cells and other eucaryotes are subdivided by membranes into many functionally distinct compartments. Each membrane-bounded compartment, or organelle, contains different proteins essential for the function of the organelle. The cell uses "sorting signals," which are amino acid motifs located within the protein, to target proteins to particular cellular organelles.
One type of sorting signal, called a signal sequence, a signal peptide, or a leader sequence, directs a class of proteins to an organelle called the endoplasmic reticulum (ER). The ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles.
Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space - a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a "linker" holding the protein to the membrane.
Despite the great progress made in recent years, only a small number of genes encoding human secreted proteins have been identified. These secreted proteins include the commercially valuable human insulin, interferon, Factor VIII, human growth hormone, tissue plasminogen activator, and erythropoeitin. Thus, in light of the pervasive role of secreted proteins in human physiology, a need exists for identifying and characterizing novel human secreted proteins and the genes that encode them. This knowledge will allow one to detect, to treat, and to prevent medical disorders by using secreted proteins or the genes that encode them.
Summary of the Invention The present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides.
Also provided are diagnostic methods for detecting disorders related to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides.
Detailed Description Definitions The following definitions are provided to facilitate understanding of certain terms used throughout this specification.
In the present invention, "isolated" refers to material removed from its original environment {e.g., the natural environment if it is naturally occurring), and thus is altered "by the hand of man" from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be "isolated" because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide.
In the present invention, a "secreted" protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a "mature" protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.
As used herein , a "polynucleotide" refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5' and 3' untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence.
Moreover, as used herein, a "polypeptide" refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined.
In the present invention, the full length sequence identified as SEQ ID NO:X
was often generated by overlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID
NO:X was deposited with the American Type Culture Collection ("ATCC"). As shown in Table 1, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Virginia 20110-2209, USA. The ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure.
A "polynucleotide" of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the cDNA within the clone deposited with the ATCC. "Stringent hybridization conditions" refers to an overnight incubation at 42°
C in a solution comprising 50% formamide, Sx SSC {750 mM NaCI, 75 mM sodium citrate), 50 mM sodium phosphate (pH 7.6)> Sx Denhardt's solution, 10% dextran sulfate, and 20 ~tg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in O.Ix SSC at about 65°C.
Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions.
Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature.
For example, lower stringency conditions include an overnight incubation at 37°C in a solution comprising 6X SSPE (20X SSPE = 3M NaCI; 0.2M NaH~PO~; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide> 100 ug/ml salmon sperm blocking DNA;
followed by washes at 50°C with 1XSSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. SX SSC).
Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide," since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone}.
The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA
or modified RNA or DNA. For example, polynucleotides can be composed of single-and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single-and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA
and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms.
The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art.
Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched , for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods.
Modifications include acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI
anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins 5 such as arginylation, and ubiquitination. (See, for instance, PROTEINS -STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W.
H. Freeman and Company, New York ( 1993); POSTTRANSLATIO.NAL
COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. I-I2 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990);
Rattan et al., Ann NY Acad Sci 663:48-62 ( 1992).) "SEQ ID NO:X" refers to a polynucleotide sequence while "SEQ ID NO:Y"
refers to a polypeptide sequence, both sequences identified by an integer specified in Table I.
"A polypeptide having biological activity" refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.) Polynucleotides and Polxpeptides of the Invention FEATURES OF PROTEIN ENCODED BY GENE NO: 1 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
MRFISQQSCECVRPCMDVYVCVYISIHVYMDAHVYLCRICKTNMR (SEQ >D
N0:309), RILRWVNCMACDLYLNKAVSVCAHVWMCMCVYISLYMYTWMP
MCIYVEYVKQT (SEQ ID N0:310), NPENQLEISFPPRRQKMKLTLDLQVSQS
SLVHSLLSSDFFSVSKEGCLWKPILLPSHFL (SEQ ID N0:311), LQTQISN
YLMFVLHILHRYTWASMYTCIEIYTHTYTSIHGRTHSQLC (SEQ ID N0:312), IHMGIHVYMYRDIYTHIHIHTWAHTLTALLRYKSHAIQLTHLNIR (SEQ ID
N0:313), and/or MKWIFTVLILTSCFFTAGICEDGICSRIQL RDKIVQSAFRQ (SEQ
ID N0:314). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, particularly neutropenia and related conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoeitic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders. More specifically, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:11 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 812 of SEQ ID NO:11, b is an integer of 15 to 826, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:11, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 2 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
KPCCPSVSNRSSVQMHQLPIQFLGQFEAHCIGFCRSFLETFYTHDPRAMHSFL
SSISSPSLPFGFSRMTSQINHLHPSPLC (SEQ ID N0:315). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, particularly neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune. hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:161 as residues: Asp-15 to Tyr-21, Pro-29 to Asn-39.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders.
Moreover, the expression of this gene product indicates a role in the regulation of the proliferation;
survival; differentiation; and/or activation of hernatopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:12 and may have been publicly available prior to conception of the present invention. Preferably, such related polynueleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 510 of SEQ ID N0:12, b is an integer of 15 to 524, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:12, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 3 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: SVFKINLKSFKQHEPWWPNRS (SEQ ID N0:316).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, including neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:162 as residues: Met-I to Arg-8, Leu-35 to Glu-41.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders. More specifically, expression of this gene product indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may also be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease. inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
WO 99122243 PCT/US9$122376 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:13 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the 5 scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 477 of SEQ ID N0:13, b is an integer of 15 to 491, where both a and b correspond to the positions of nucleotide residues shown in 10 SEQ ID N0:13, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 4 This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune disorders, including neutrophenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:163 as residues: Asn-45 to Thr-58.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment andlor prevention of a variety of immune disorders. In particular, this gene product may play a role in regulating the proliferation; survival; differentiation; andlor activation of hematopoietic cell lineages, including blood stem cells. Furthermore, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, IO rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
I5 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:14 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
20 Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 389 of SEQ ID N0:14, b is an integer of 15 to 403, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:14, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 5 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GTRSFSVPSYLRLTGSLMCYLLLLLIQTAELLIHPQGLQAVSNGESALKGTRPTF
SSPFILVTEGRKEWEGVFLSSGWKGNTLSNYYISLVFYYSRILQPYFYCLWGK
LEMVTLIRSVWRGINGGDKISVGFGKC (SEQ ID N0:317), WMERKHTVKLL
YLLGFLLQNSPAIFLLSMGEVGDGDLD (SEQ ID N0:318) SNGESALKGTRP
TFSSPFILVTE (SEQ ID N0:319), and/or LSNYYISLVFYYSRILQPYFYCLW (SEQ
ID N0:320). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.
This gene is expressed primarily in the breast and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, reproductive, or neural disorders, such as cancers of the breast, lymph system and brain. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive, immune, and central nervous systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, neural, breast, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:164 as residues: Leu-31 to Phe-38, Glu--47 to Trp-52.
The tissue distribution in breast and brain tissue indicates that polynucleotides and polypeptides cowesponding to this gene are useful for the diagnosis and treatment of cancers in the breast, lymph system, and brain. Moreover, the protein product of this gene may be useful for the detectionltreatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:15 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 799 of SEQ ID NO:15, b is an integer of I S to 813, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:15, and where b is greater than or equal to a + I4.
FEATURES OF PROTEIN ENCODED BY GENE NO: 6 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:165 as residues: Ser-49 to Leu-54.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of a variety of immune disorders. Moreover, the expression of this gene product indicates a role in regulating the proliferation; survival;
differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lease tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:16 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 250 of SEQ ID N0:16, b is an integer of 1 ~ to 264, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:16, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 7 The translation product of this gene shares sequence homology with neurotoxin which is thought to be important in neural diseases. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
EKDFMQGSDAGHGGTHIYRALVQWPLAWVFYLSHAKTHWGEELRFSFRRKN
LRLREAMRHETCQVTQLVA GKADSNLCLRDSETWFWPPLWAACSSLQATA
CRLSSPSKGLGASRECPWLASGRAALVSFL (SEQ ID N0:321), SLRVKGRKPR
LLYHSPARGTLWMLPGLCDCL ICRQWLVERSRLPRVGARTRFQSP SDTGWS
QLCQLPAV (SEQ ID N0:322), and/or ERSRLPRVGARTRFQSPSDTGWSQLC
(SEQ ID N0:323). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and neural diseases, particularly neurodegenerative disorders, such as Alzheimers or Parkinson's. Similarly, polypeptides and antibodies directed to 10 these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hemaopoietic, neural, and cancerous and wounded tissues) or bodily 15 fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:166 as residues: Gln-2 to Gly-10, Asp-77 to Phe-82.
The tissue distribution in neutrophils combined with the homology to the conserved neurotoxin protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune and neural diseases.
Similarly, the protein product of this gene may be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders. or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular WO 99r12243 PCT/US98/22376 system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:17 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 506 of SEQ ID NO: I7, b is an integer of 15 to 520, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: I7, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 8 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KHAFLMAHQFCVLSLAMQWSSCFQLVALPYLSL (SEQ ID
N0:324). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, and/or prevention of immune disorders. Furthermore, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimrnune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease. scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:18 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 979 of SEQ ID N0:18. b is an integer of 15 to 993, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:18, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 9 When tested against Jurket and PC12 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) and (early growth response gene 1) promoter elements. Thus, it is likely that this gene activates T-cells and sensory neurons through the JAK-STAT and EGR1 signal transduction pathways. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
WO 99r12243 PCT/US98/22376 sy Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. EGR1 is a separate signal transduction pathway from Jak-STAT, genes containing the EGR 1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: MRPLCVLLPWPCWQWGGLGSASPIRPQAPPGQAAHAVP
LPRAQHLAQRSRQ (SEQ ID N0:325). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.
This gene is expressed primarily in breast, lymph nodes, spleen, and to a lesser extent, in liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, immune, or hepatic disorders, particularly cancers of the breast, liver. and lymph system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast, liver and lymph system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, breast, immune hematopoietic, hepatic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, breast milk. bile. serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder; relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:168 as residues: Pro-54 to Gly-57.
The tissue distribution in breast and immune tissues combined with the detected EGR 1 and GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancers of the breast and lymph systems. Moreover, the GAS and EGR 1 activity strongly indicates that the protein product of this gene may play an integral role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, such proliferative tissues rely on finely regulated decisions involving cell differentiation and/or apoptosis. Thus this protein may also be involved in regulating apoptosis or tissue differentiation and, thus could be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:19 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 445 of SEQ ID N0:19, b is an integer of 15 to 459, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:19, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 10 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARGLRSPHGAAGVVRGDGGGKKGEDPYSPILFQ
SERIPRLIYLPVISSEENS (SEQ ID N0:326). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in an LPS induced neutrophil cDNA library.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune system disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders, for example, in ameliorating an abberant neutrophil reponse to infectious agents. Similarly, the expression of this gene product may suggest a role in 5 regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may also be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene 10 product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia. neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to 15 transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed 20 progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:20 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded, from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 541 of SEQ ID N0:20, b is an integer of 15 to 555, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:20, and where b is greater than or equal to a + 14.
WO 99/22243 PCTIUS98I2237b FEATURES OF PROTEIN ENCODED BY GENE NO: 11 This gene is expressed primarily in prostate cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive or immune system disorders, particularly prostate cancer.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, prostate, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:170 as residues: Pro-14 to Asp-25, Leu-51 to V al-63.
The tissue distribution in prostate tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive system disorders such as cancer, particularly prostate cancer.
Similarly, the expression within prostate cancer tissue, a cellular source marked by proliferating cells, indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders not limited to prostate tissue. Further, such tis>ues rely on decisions involving cell differentiation and/or apoptosis. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 651 of SEQ ID N0:21, b is an integer of 15 to 665, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:21, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 12 The polynucleotide sequence of this gene may have a frame shift. Therefore the preferred signal peptide may reside in a frame other than the associated polynucleotides of this gene. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
KSLSCSFLFLAFWLRRMGQTMCVCVCVCVCVCVRTWVYLYEPVKF RSPLIYV
NLPTS (SEQ ID N0:327), and/or KLGFTMLARLVSNSXTSGDLPSSASQNAGI
KGMSYRAWPYSYFLIRKNKQT NKQTKTNPQLGENKHCRNLKVSWSKNYFL
(SEQ ID N0:328). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune system disorders, particularly immunodeficiencies such as lupus and AIDS, or inflammatory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Moreover, this gene product may play a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:22 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 763 of SEQ ID N0:22, b is an integer of 15 to 777, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:22, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 13 When tested against Jurket and U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element. Thus, it is likely that this gene activates T-cells and promyelocytic cells through the JAK-STAT signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT
pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
ERGQGGSSRNVAGSDLVFPAVFVSXLC (SEQ ID N0:329), GSPQGPS VALGSRQCWSRPLRRGGRGAAVEMWRGPTWCFRPSLCLCCVCGV
SFGLYVPHGFSLSMCVSAP GSAWLSLVYSICLARGSMSXRXSSRXSLV
ASGAS VLLVCFW VXADPG VG VS VPRAXVSGLWWCVSPSACLXLAPTKPPP
XLSFSLSIFPFSSNPSK (SEQ ID N0:330), and/or TIASLQPTALNHLIWRGW
KRKGRLRERKRGXGGAWLGPXRGRQMDSHTTRDQRQXLGEQRHPLLGLXA
PRSKPTKQMPQMQPGXPEKKXXLTWNHGLDRWNTQGTARQSLGQK
HTWRD (SEQ ID N0:331 ). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adipose tissue and the brain.
Therefore, polynucleotides arid polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, metabolic or neural disorders, particularly obesity, and neurodegenerative or central nervous system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes far differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.adipose, neural, immune, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in adipose and neural tissues, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of obesity and disorders of the brain and central nervous system. Similarly, the protein product of this gene may be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism. and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or 5 survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. In addition, the protein product of this gene may also be beneficial in detecting, treating, or preventing neural disorders which occur secondary to aberrant fatty acid metabolism in neural 10 tissues, such as for aberrations in myelin sheath development, or associated autoimmune disorders of neural tissue or the overlying integument. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available 15 and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:23 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more 20 polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 526 of SEQ ID N0:23, b is an integer of 15 to 540, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:23, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 14 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARGPGTEGCEPWLQLQDRRER (SEQ ID N0:332), and/or MSSGTNSFFTLMALNSPTGDSGSRITVSPPRVHPVKSGRGRASDLLLTRFLAPR
SALWS {SEQ ID N0:333). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in a cDNA library from IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune system disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of conditions where lymphocytes show abberant response to an infectious agent.
Similarly, this gene product may play a role in regulating the proliferation;
survival;
differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:24 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 470 of SEQ ID N0:24, b is an integer of 15 to 4$4, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:24, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 15 This gene is expressed primarily in ovaries, tonsils, and CD34 positive bone marrow stem cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, immune, developmental, or hematopoietic disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, ovarian, immune, tonsil, umbilical, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in ovarian and tonsil tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune and reproductive system disorders. Similarly, expression of this gene product in tonsils indicates a role in regulating the proliferation; survival;
differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, WO 99!22243 PCT/US98/22376 neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, S rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:25 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 693 of SEQ ID N0:25, b is an integer of 15 to 707, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:25, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 16 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocyctic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: HEYHLLSSRHILGSVLRLDVC SALWS (SEQ ID N0:334).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune. hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells combined with the detected GAS
biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, treatment, andlor prevention of immune disorders.
Specifically, the expression of this gene product in neutrophils indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity: immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:26 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 779 of SEQ ID N0:26, b is an integer of 15 to 5 793, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:26, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 17 This gene is expressed primarily in the spinal cord.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, any of a variety of nervous system and neuromuscular disorders, particularly amyotropic lateral sclerosis, musculuar dystrophy, and inherited and non-inherited forms of chorea. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system and neuromuscular systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, neuromuscular, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spinal cord tissue indicates that this gene could be used for the treatment of spinal cord and related injuries. The protein product of this gene could be injected into the spinal cord to promote or control growth following injuring or degeneration. Alternatively cells expressing this gene could be injected or transferred into the spinal cord by other means as a treatment promoting the regulation of growth following spinal cord injury or degeneration. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease> Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:27 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 624 of SEQ ID N0:27, b is an integer of 15 to 638, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:27, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: Z8 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS {gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
FILFILEYDMLWKSLYTNSSAYGYVIASYFCLLGIKLLVKQKKXKKKTRGGAR
X PIRPXVESYYKSXAVVLQRRGLGKNLGG (SEQ ID N0:335). Poiynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in the adrenal gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine disorders, particularly disorders of the adrenal gland.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the adrenal gland. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endocrine, adrenal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a 1 S disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in adrenal tissue, combined with the detected GAS
biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many poiynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:28 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 514 of SEQ ID N0:28, b is an integer of 15 to 528, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:28, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 19 This gene is expressed primarily in the placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types {e.g.placental, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:178 as residues: His-15 to Trp-20, Pro-48 to Ala-54.
The tissue distribution in placental tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of reproductive disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:29 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 905 of SEQ ID N0:29, b is an integer of 15 to 919, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:29, and where b is greater than or equal to a + 14.
WO 99/22243 PCT/US98/223~6 FEATURES OF PROTEIN ENCODED BY GENE NO: 20 The translation product of this gene shares sequence homology with human erythrocyte membrane anion-transport protein which is thought to be important in autoimmune diseases. Furthermore, the translation product of this gene also has homology to a human gnlIPIDId1026838 (AB012130) sodium bicarbonate cotransporter2 which is.thought to be important in maintaining cellular homoestasis.
Contact of cells with supernatant expressing the product of this gene was found to increase the permeability of the plasma membrane of enterocytes and renal mesangial cells to calcium. Thus it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product binds a receptor on the surface of the enterocytes and renal mesangial cells. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating cellular processes within enterocytes and renal mesangial cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
RVSSHLFRLFGGLILDIKRKAPFFLSDFKDALSLQCLASILFLYCACMSPVITFG
GLLGEATEG RIVSTKIGSGQAFSSSEASVCMHLSHYSYFYLKSLPTA (SEQ ID
N0:336), FRLFGGLILDIKRKAPFFLSDFKD {SEQ ID N0:337), FLYCACMSPV
ITFGGLLGEATEG (SEQ ID N0:338), andlor SSSEASVCMHLSHYSYFYLKSL
(SEQ ID N0:339). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3.
This gene is expressed primarily in human testes tumor.
2~ Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or reproductive disorders, particularly autoimmune diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues}
or cell type(s). For a number of disorders of the above tissues or cells. particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, testicular, and cancerous and wounded tissues) or bodily fluids (e.g. lymph. seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in testis, the homology to an erythrocyte membrane antion-transport protein, in addition to, the detected calcium flux biological activity 5 indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of autoimmune diseases and other immune diseases such as cancer, particularly in, but not limited to, testicular tissue. Similarly, the translation product of this gene may be important in maintaining normal, cellular homeostasis.
Therefore, the protein, as well as antibodies directed to the invention, is beneficial as a therapeutic in 10 order to ameliorate conditions related to aberrant cellular pH regulation (for example, use antibodies to decrease the presence of the protein, or possibly in gene therapy applications in order to replace a defective form, or alternatively, increase the expression of either the endogenous or modified form of the invention).
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker 15 and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:30 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the 20 scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 850 of SEQ ID N0:30, b is an integer of 15 to 864, where both a and b correspond to the positions of nucleotide residues shown in 25 SEQ ID N0:30, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 21 30 This gene is expressed primarily in the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, which include, but are not limited to, disorders of the 35 brain and central nervous system, such as neurodegenerative conditions and/or depression. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:180 as residues: His-13 to Leu-18.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders of the brain and central nervous system. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease., Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:31 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 905 of SEQ ID N0:31, b is an integer of 15 to WO 99/22243 PC'f/US98/22376 919, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:31, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 22 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
PCLQVIGIDFCRLLLMCLVLKRNLTVPFSSYSPLKTITCITSEQIAWSNFFRQKL
GVRAK FFQGACLHTSKVVICLNLPIISIQRADIRMWWLVVNTPYARGVNN
(SEQ ID N0:340). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in the spinal cord.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, any of a variety of nervous system and neuromuscular disorders including, but not limited to, amyotropic lateral sclerosis, musculuar dystrophy, and inherited and non-inherited forms of chorea. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system and neuromuscular systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spinal cord indicates that this gene could be used for the treatment of spinal cord injuries. The protein product of this gene could be injected into the spinal cord to promote or control growth following injuring or degeneration.
Alternatively cells expressing this gene could be injected or transferred into the spinal cord by other means as a treatment promoting the growth or regulation of growth following spinal cord injury or degeneration. This gene may also be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases.
peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:32 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 942 of SEQ ID N0:32, b is an integer of 15 to 956, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:32, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 23 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VVSVCVLETGQLGPAALCRSV (SEQ ID N0:341).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, which include, nut are not limited to, inflammatory diseases or neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid} or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treament of the inflammatory conditions. Moreover, This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:33 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 552 of SEQ ID N0:33, b is an integer of 15 to Sb6, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:33, and where b is greater than or equal to a + 14.
WO 99!22243 PGT/US98/22376 FEATURES OF PROTEIN ENCODED BY GENE NO: 24 S In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
NISVHGFPVPCLRQRLQGPCHPKCCPHXISSGKPRSSFSPSSYHCKFSRNATLL
VVPNIFSYMQSSFLIPQTSKYYILXPYAXTXRPIKXIFKQAKQ (SEQ ID N0:342), IYNDMMMEKKKTEVYQKRXSGDNTWGGKGLVAFVSSMEQGIHVQRCFIANL
10 KFSSPGV (SEQ ID NO: 343), YDDGEKEDRGLPEEMXWGQHLGWQGPCSL
CLKHGTGNPCTEMFYCQFKIFIS WCLIPLVFARLGDFRDRPGWIFSWRYHLKH
TVWGGYNIIML (SEQ ID NO: 344), TPGDENFKLAIKHLCTWIPCS (SEQ ID NO:
345), IRHEIFLTIESFCPSAPRGEDDDNLLRTSRVPDI (SEQ ID N0:346), IRGSIP
GHKKMHLS FNVAAQWSLLKPLVLREEGALFLTHDQLESKNSWTLSIGPRV
KGKQSHSTVQLANILHVFXAPDXYHFVNTSLQLFLEYTVMCMLCENK QKT
LGR (SEQ ID N0:347), EPEVTQVXSXELTFQ PRKAGAKVTAGKSHHQVIHWE
FEIMLSSYSTDVPLWFLKFFSSNLPQTYFPHSGVKKWGSCFSLPWRDSPPLT
FISLLSSHLTTFHLYHLHHGIICLGFSVYFHRAYTSLCILETAVGSY (SEQ ID
20 N0:348), WSLLKPLVLREEGALFLTHDQLESK (SEQ ID N0:349), WFAKKK
GKQSHSTVQLANILHV (SEQ ID N0:350), AGKSHHQVIHWEFEIMLSSYSTDVP
(SEQ ID N0:351), and/or HGIICLGFSVYFHRAYTSLCILETAV (SEQ ID N0:352).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in smooth muscle.
25 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, muscular or vascular disorders, which include, but are not limited to defective organ innervation; deficiencies in neuronal survival; peristaltic abnormalities;
30 digestive disorders; perturbations of the vasculature. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the smooth muscle, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types 35 (e.g., cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in smooth muscle tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or S treatment of disorders that result from failures of normal smooth muscle function. For example, this.gene product may represent a soluble factor produced by smooth muscle that regulates the innervation of organs or regulates the survival of neighboring neurons. Likewise, it may be involved in controlling the digestive process, and such actions as peristalsis. Similarly, it may be involved in controlling the vasculature in areas where smooth muscle surrounds the endothelium of blood vessels. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:34 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1550 of SEQ ID NO:34, b is an integer of 15 to 1564, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:34, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 25 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KRLTINARVHLWTLKSVPL (SEQ ID N0:353), EYVFNMX
XYSKSRAISPLSGPYTPRGTTPLPIIPEPGARQRDHPAS LKYAKIIQTKLFAL
PYPKETSMKAVA (SEQ ID N0:354), andlor ETVPPRSSQFLKITXGPARSMSLIX
XAIQNPEPYLLYLALIPQEALLLYLSSQSQVPGNETTPPV (SEQ ID N0:355).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not linvted to, immune system disorders. which include, but are not limited to lupus, inflammatory conditions, and immunodeficiencies such as AIDS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:184 as residues: Ser-21 to Thr-34, Thr-38 to Glu-43.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Expression of this gene product in T-cells indicates a role in regulating the proliferation; survival; differentiation;
and/or activation of hematopoietic cell lineages, including blood stem cells. This Gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:35 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1021 of SEQ ID N0:3S, b is an integer of 1S
S to 1035, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:3S, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 26 The translation product of this gene was determined to have homology to the human IB3089A protein which is thought to play an important role in tumor suppression {See Genbank Accession No.gi13041877 (AF027734)).In specific embodiments, polypeptides of the invention comprise the following amino acid 1 S sequence: NEVSFSLSLGFSPREFARWKVNNLAL ERKDFFSLPLPLAPEFIRNI
RLLGRRPNLQQVTENLIKKYGTHFLLSATLGGKQHHNPKLIGCQTIGNNV
KTRVA (SEQ ID N0:3S6), VPYFLIRFSVTCCRLGLLPRRRMFRIN SGARGNG
KLKKSFLSRAK LFTFQRANSLGEKPRDKEKLTSFQSKRHKI (SEQ ID N0:3S7), and/or EMSAVLFNQIFCNLLQIGSPSKEANVPDKLWGKRQWQTEEVLPFQSQV
VHLPTGKLPGGKAKG (SEQ ID N0:3S8). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human fibrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 2S biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders afflicting endothelial, muscular. and extracellular matrix tissues, which include, but are not limited to fibrosarcomas and bladder cancer.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the integumentary system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endothelial, urogenital,renal, muscular, and cancerous and wounded tissues) or bodily fluids {e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken 3S from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:185 as residues: Pro-49 to Asp-68.
The tissue distribution in human fibrosarcoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of various cancers, particularly fibrosarcomas and fibroids. Moreover, the expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many poiynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:36 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 606 of SEQ ID N0:36, b is an integer of IS to 620, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:36, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 27 This gene is expressed primarily in human tonsil.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, which include, but are not limited to inflammation and infectious diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids {e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an 5 individual not having the disorder.
The tissue distribution in tonsils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis of inflammation and infectious diseases. Moreover, this gene product may play a role in regulating the proliferation;
survival; differentiation; and/or activation of hematopoietic cell lineages, including 10 blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological 15 disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as 20 autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, 25 antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:37 and may have been publicly available prior to conception of the present 30 invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 959 of SEQ ID N0:37, b is an integer of I S to 35 973, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:37, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 28 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
HYHGSGFLIKEFGSFLSLLCMLSCPYVFCHGMLEQEVPSSVVSPSTLDF PTSR
TVNKFLFKLPSLWYSVIATQNGLKQKIRETFLFVQFSQMPRWHKLE (SEQ ID
N0:359}. Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adipose and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. metabolic or neural conditions, which include but are not limited to obesity and disorders of the brain and central nervous system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, metabolic tissues, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neural and adipose tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of obesity and disorders of brain and central system. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. In addition, considering the expression within both adipose tissue and brain indicates that the protein may be benefical either as a target for gene therapy, or as a novel therapeutic to ameliorate conditions affecting myelin sheath development in neurons, or other disorders involving neural tissue which occur secondary to aberrant fatty-acid metabolism. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:38 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 824 of SEQ ID N0:38, b is an integer of 15 to 838, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:38, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 29 The gene encoding the disclosed cDNA is thought to reside on chromosome I 1.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11. One embodiment of this gene comprises polypeptides of the following amino acid sequence:
FCKHNGSKNVFSTFRTPAVLFTGIVALYIASGLTGFIGLEVVAQLFNC (SEQ ID
N0:360). An additional embodiment is the polynucleotides encoding the polypeptides.
This gene is expressed primarily in suppressor T cells, endothelial cells, dendritic cells, and infant brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include.
but are not limited to, immune system disorders related to abnormal activation of T
cells.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the S immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. hematopoietic, developmental;
neural, immune, endothelial, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e.; the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:188 as residues: Tyr-14 to Leu-24, Pro-S9 to Gln-66.
The tissue distribution in immune cells indicates that polynucleotides and 1S polypeptides corresponding to this gene are useful for treating disorders of the immune system related to altered activation of T cells. Furthermore. this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of immune disorders.
Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility 2S in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:39 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more 3S polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to S93 of SEQ ID N0:39, b is an integer of 1 S to a9 607, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:39, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 30 This gene is expressed primarily in the fetus and in tumor cell types.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of rapidly growing tissues such as cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of rapdiIy growing tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. fetal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene primarily in the developing fetus indicates a role in the treatment and/or detection of developmental disorders and growth defects. In addition, expression in tumor cell types indicates a role in the detection and/or treatment of tumors. Furthermore, expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:40 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 868 of SEQ ID N0:40, b is an integer of 15 to 882, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:40, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 31 This gene is expressed primarily in salivary gland, and to a lesser extent, in 10 other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to> digestive and immune disorders. Similarly, polypeptides and antibodies 15 directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the salivary gland and other glands of the exocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. exocrine, digestive. cancerous and 20 wounded tissues) or bodily fluids (e.g. lymph, serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
25 N0:190 as residues: Glu-25 to Gly-31, Tyr-62 to Thr-68.
The tissue distribution in salivary gland tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of digestive and immune system disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the 30 above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:41 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the 35 scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 945 of SEQ ID N0:41, b is an integer of 15 to 959, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:41, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 32 The gene encoding the disclosed cDNA is thought to reside on chromosome 12.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12.
This gene is expressed primarily in brain tissue of adults, as well as infants.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. neurodegenerative and behavioural disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central and peripheral nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:191 as residues: Ser-16 to Val-33.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. Furthermore, expression of this gene product within the brain indicates that it may be involved in neuronal survival;
synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:42 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 861 of SEQ ID N0:42, b is an integer of 15 to 875, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:42, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 33 This gene is expressed primarily in the synovium.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases affecting the synovial lining including arthritis and autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the musculo-skeletal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. endothelial, skeletal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for use as a factor that may protect against articular damage or promote growth of the cells in articulating joints.
Furthermore, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g.
arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:43 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 616 of SEQ ID N0:43, b is an integer of 15 to 630, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:43, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 34 When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus. it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the 3ak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in B-cell lymphoma cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune disorders, such as diseases of B-cell lineage including lymphomas lymphoblastic leukemias, myelomas and hairy cell leukemia.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:193 as residues: Lys-82 to Pro-90.
The tissue distribution and biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for for the treatment and or diagnosis of diseases of B-cell lineage including cancer. This factor may be useful in the terminal differentiation of malignant cells or may act as a growth factor for B-cell proliferation or differentiation, which is supported by the biological assay data. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:44 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 557 of SEQ ID N0:44, b is an integer of 15 to 571, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:44, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 35 When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore. activation of the Jak-STAT pathway. reflected by the binding of the GAS
5_5 element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in osteoclastoma derived stromal cells, placenta, pancreas and several tumor derived cells and to a lesser extent in brain, melanocytes, dendritic cells, and several other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(sj or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, tumors of the pancreas, uterus, ovary, bone, or adrenal gland.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. placenta, pancreas. cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating or diagnosing tumors of the reproductive organs, pancreas, or bone marrow. Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, andlor prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g.
diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:45 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 916 of SEQ ID N0:45. b is an integer of 15 to 930, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:45, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 36 When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay. Thus, it is likely that this gene activates leukemia cells through the Jak-STAT signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the ISRE
element, can be used to indicate proteins involved in the proliferation and differentiation 1 S of cells.
This gene is expressed primarily in kidney and to a lesser extent in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. renal and nervous system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders ' of the above tissues or cells, particularly of the renal and nervous systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.renal, urogenital, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:195 as residues: Lys-117 to Lys-126.
The tissue distribution of this gene in kidney tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of renal disorders including kidney failure and Wilms Tumor in addition to the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:46 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 423 of SEQ ID N0:46, b is an integer of 15 to 437, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:46, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 37 One embodiment of this gene comprises polypeptides of the following amino acid sequence:
MPKPGAATQRTLLCLPRLHPASGPPLPXAGPLRGLRQLPALPVPAASCRRRPAP
RLCAAGPCTVGPAASPHAPPHGCPPPASLAHV AHRQSVSGTVCLGLRDGHV
RGGCAAVRGXAALPWDAAAAGPDHMGVGSGPALL (SEQ ID N0:361). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in pituitary and to a lesser extent in thymus and breast.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, metabolic and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). 1~or a number of disorders of the above tissues or cells, particularly of the endocrine and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types or cell types (e.g. thymus, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of endocrine, metabolic, and immune disorders including growth and developmental defects, in addition to the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:47 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1010 of SEQ ID N0:47, b is an integer of 1S
to 1024, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:47, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 38 This gene is expressed primarily in hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular disorders such as stroke, aneuyrism, cardiac arrest, hemorrhage. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. circulatory system, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:197 as residues: Cys-14 to Gly-23, Met-4S to Gly-51.
The tissue distribution of this gene solely in hemangiopericytoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and or detection of vascular disorders including hemorrhaging, aneuyrism, stroke and cardiac arrest. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:48 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 449 of SEQ ID N0:48, b is an integer of 15 to 463, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:48, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 39 The translation product of this gene shares sequence homology with a serine protease which is thought to be important in regulating the availibility and action of proteins in vivo.
This gene is expressed primarily in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. disorders of the central nervous system related to abnormal growth factor regulation, including neurodegenerative conditions such as Alzheimers disease and psychiatric illness such as Schizophrenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Central Nervous System, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. CNS, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:198 as residues: Ser-17 to Gln-22.
5 The tissue distribution in neural tissue, combined with the homology to serine proteases indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders of the central nervous system including neurodegenerative diseases and psychiatric disorders. Furthermore, expression of this gene product within cerebral tissue indicates that it may be involved in neuronal survival;
synapse formation;
10 conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. It may also be useful in the treatment of such neurodegenerative disorders as schizophrenia; ALS; or Alzheimer's.Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
15 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:49 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
20 Accordingly, preferably excluded from the present invention are one or more polynucIeotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 871 of SEQ ID N0:49, b is an integer of 15 to 885, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:49, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 40 This gene is expressed primarily in CD34 depleted buffy coat.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
WO 99/22243 PCT/US9$/22376 immune, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in CD34 depleted huffy coat tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders of the immune system including autoimmune diseases. Furthermore, expression of this gene product in CD34 depleted huffy coat indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as; antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy-targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences we related to SEQ
ID NO:50 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 833 of SEQ ID NO:50, b is an integer of 15 to 847, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:50, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 41 This gene is expressed primarily in B-cell lymphoma cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of B-cell lineage including lymphomas lymphoblastic leukemias, myelomas and hairy cell leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues j or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immunce cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for for the treatment and or diagnosis of diseases of B-cell lineage including cancer. This factor may be useful in the terminal differentiation of malignant cells or may act as a growth factor for B-cell proliferation or differentiation. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:S 1 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 566 of SEQ ID NO:S 1, b is an integer of 15 to 580, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:51, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 42 This gene is expressed primarily in brain and CD34 depleted huffy coat.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune disorders particularly those of the central nervous system such as multiple sclerosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, neural, and cancerous and wounded tissues) or bodily fluids (e.g. lymph. amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:201 as residues: Pro-35 to Ala-40.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating autoimmune disorders such as multiple sclerosis. Furthermore, expression of this gene product in CD34 depleted huffy coat indicates a role in the regulation of the proliferation; survival;
differentiation;
andlor activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:52 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 584 of SEQ ID N0:52, b is an integer of 15 to 598, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:52, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 43 This gene is expressed primarily in tissues of the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological and neurodegenerative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. CNS, brain, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful as a neuronal protective agent and as a growth factor for cells of the central or peripheral nervous system.
Furthermore, expression of this gene product within the brain indicates that it may be involved in neuronal survival; synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:53 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 557 of SEQ ID N0:53, b is an integer of 15 to 571, where both a and b correspond to the positions of nucleotide residues shown in 10 SEQ ID N0:53, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 44 15 The gene encoding the disclosed cDNA is thought to reside on chromosome 9.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 9.
This gene is expressed primarily in embryo and fetal tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as 20 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above 25 tissues or cells, particularly of the embryo and fetal tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
fetal tissues, develpomental, cancerous and wounded tissues) or bodily fluids (e.g.
lymph, amniotic fluid, serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the 30 standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in embryonic and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of developmental disorders. Furthermore, the tissue distribution indicates 35 that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other proliferative disorders.
Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division.
Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:54 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1233 of SEQ ID N0:54, b is an integer of 15 to 1247, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:54, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 45 The gene encoding the disclosed cDNA is thought to reside on chromosome 2.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2.
This gene is expressed primarily in infant brain, placenta, sane immune tissues.
and, to a lesser extent, in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and immune disorders. Similarly. polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the early developmental stage tissues and immune tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:204 as residues: Val-32 to Met-39, Leu-44 to Val-49.
The tissue distribution in fetal and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of developmental and immune disorders. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other proliferative disorders.
Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division.
Additionally, the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and/or survival of hematopoietic cell lineages. In such an event, this gene may be useful in the treatment of lymphoproliferative disorders, and in the maintenance and differentiation of various hematopoietic lineages from early hematopoietic stem and committed progenitor cells. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. The protein product of this gene is useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome. meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder; learning disabilities, ALS, psychoses . autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover; the gene or gene product may also play a role in the treatment andlor detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies 'directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:55 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 834 of SEQ ID NO:55, b is an integer of 15 to 848, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:S~, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 46 When tested against Jurkat T-cells, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates T-cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in brain tissues, and to a lesser extent, in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neuronal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, brain, cancerous and wounded tissues) or bodily fluids {e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:205 as residues: Ser-33 to Ser-44.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal and immune system disorders. Furthermore, expression of this gene product in T-cells, as well as the observed biological activity of this gene product, indicates that this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Alternatively, the expression within brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries. ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities. ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NU:56 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 655 of SEQ ID N0:56, b is an integer of 15 to 669, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:56, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 47 When tested against U937 Myeloid cell lines, supernatants removed from cells 10 containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay.
Thus, it 15 is likely that this gene activates leukemia cells through the Jak-STAT
signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT
pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the 20 binding of the GAS element, can be used to indicate proteina involved in the proliferation and differentiation of cells. Contact of cells with supernatant expressing the product of this gene increases the permeability of bovine chondrocytes to calcium.
Thus, it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product of this gene binds a receptor on the surface of 25 the chondrocyte cells. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating bone cells.
This gene is expressed primarily in breast and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 30 biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pregnancy disorders including miscarriage. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast and placenta , expression of this 35 gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. placental tissues, breast, bone, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in both placenta and breast indicates a role for this protein in the treatment and/or detection of miscarriages in suspect individuals, of birth defects, of breast cancer, and female infertility. Furthermore, the biological assay data strongly indicates that the translation product of this gene is actively involved in the initiation of several signal transduction pathways and the activation of several cell types.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:57 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 666 of SEQ ID N0:57, b is an integer of 15 to 680, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:57, and where b is greater than or equal to a + 14 FEATURES OF PROTEIN ENCODED BY GENE NO: 48 The gene encoding the disclosed cDNA is thought to reside on chromosome 11.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11. One embodiment of this gene comprises the polypeptides of the following amino acid sequence:
MWGQPRPVDSVWSSSIPKKSVESNDNKSHLHKREH (SEQ ID N0:362), MTTKAIFTKGNIDSLSFKSNMWSVYI (SEQ ID N0:363). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in the pancreas.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pancreatic related disorders such as diabetes. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. pancreas, endocrine, metabolic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, bile, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in pancreatic tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment/detection of endocrine disorders and metabolic disorders associated with the pancreas including diabetes, panereatitis, and pancreatic cancer. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:58 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 510 of SEQ ID N0:58. b is an integer of 1 S to 524, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:58, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 49 This gene is expressed primarily in chondrosarcoma tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, including diseases of the skeletal system, particularly with respect to the cartilagenous structures and also cancer of these tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. bone, connective, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in chondrosarcoma tumors indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment/diagnosis of cartilage disorders including arthritis and cancer. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:59 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To Iist every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 4I3 of SEQ ID N0:59, b is an integer of 15 to 427, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:59, and where b is greater than or equal to a + 14 FEATURES OF PROTEIN ENCODED BY GENE NO: 50 The translation product of this gene shares sequence homology with sorbinwhich is thought to be important in the manufacture of vitamin C.
Additionally, sorbin is thought to be important in the process of stimulating water and electrolyte absorption in various cells in the body. Porcine Sorbin has activity in stimulating water and electrolyte absorption across mucosa. It has been pursued as a regulator of electrolyte absorption in the nasal and enteric mucosa. This gene was identified in hypothalamus suggesting that it could play a role in the CNS regulation of water or electrolyte absorption.
This gene is expressed primarily in human hypothalamus tissue from a patient suffering from Alzheimer's disease.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurologic disorders (eg. Alzheimer's disease). Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunoIogical probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:209 as residues: Leu-29 to Leu-37, Gln-65 to Asp-70, Gln-85 to Gly-95.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Alzheimer's disease. Additionally, the translation product of this gene, based upon its homology to the porcine sorbin, could be useful for the detection and/or amelioration of disorders involving the CNS regulation of water or electrolyte absorption.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:60 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1249 of SEQ ID N0:60, b is an integer of 15 to 1263, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:60, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 51 This gene is expressed primarily in synovium. and to a lesser extent, in other tissues.
5 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. synovial diseases such as synovial sarcoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes 10 for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the synovium. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
connective tissues. cancerous and wounded tissues) or bodily fluids le.g.
lymph.
serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level. i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in synovium indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of '.0 synovial diseases such as arthritis. Furthermore, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. trauma, tendonitis. chrondomalacia and inflammation). such as in the diagnosis or treatment of various autoimmune disorders 5 such as rheumatoid arthritis. lupus. scleroderma. and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita. familial osteoarthritis.
Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or ~ immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:61 and may have been publicly available prior to conception of the present invention. Preferably. such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 706 of SEQ ID N0:61, b is an integer of 15 to 720, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:61, and where b is greater than or equal to a + I4.
FEATURES OF PROTEIN ENCODED BY GENE NO: 52 This gene is expressed primarily in immune tissues and fast-growing tissues, such as tumor and early-stage developmental tissues, and, to a lesser extent, in some other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and growth related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune tissues and fast-growing tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. developmental, immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:211 as residues: Ala-28 to Ala-47.
The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of immune and growth related diorders. Furthermore, expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:62 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the S scope of the present invention. To list every related sequence is cumbersome.
Accordingly,,preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to S7S of SEQ ID N0:62, b is an integer of 1S to 589, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:62, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: S3 1 S One embodiment of this gene comprises polypeptides of the following amino acid sequence: DSXLDRRPSGPDVKFLSNKHHFSMVC (SEQ ID N0:364). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in spleen, and to a lesser extent, in a range of hematopoetic cell types.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoeitic disorders. Similarly, polypeptides and antibodies directed to these poiypeptides are useful in providing immunological probes 2S for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoetic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. spleen, immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:212 as residues: Cys-2S to Trp-30.
3S The tissue distribution of this gene in spleen tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma.
immunodeficiency diseases and leukemia. Expression of this gene product in spleen indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other S processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation andJor proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a 1 S tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences we related to SEQ
ID N0:63 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 672 of SEQ ID N0:63, b is an integer of 1 S to 686, where both a and b correspond to the positions of nucleotide residues shown in 2S SEQ ID N0:63, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 54 This Qene is expressed primarily in human normal breast, and to a lesser extent.
in dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are 3S not limited to, glandular problems involving cells of epithelial origin including breast cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the female endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. breast, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
NO:213 as residues: Ser-32 to Asn-44.
The tissue distribution in breast tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or treatment of both malignant and non-malignant problems of the breast tissues, including cancer.
Alternatively. the expression in dendritic tissue indicates polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
iD N0:64 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 438 of SEQ ID N0:64, b is an integer of 15 to 452, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:64, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 55 When tested against U937 Myeloid cell lines, supernatants removed from cells 5 containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
10 Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in early stage human tissues, immune tissues, and to a lesser extent, in other tissues such as prostate.
1 S Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, development and immune related diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes 20 for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and early stage human tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine. synovial fluid and 25 spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in embryonic and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis 30 and treatment of developmental and immune related diseases. The biological activity data supports the assertion that the translation product of this gene is useful in the treatment andlor diagnosis of diseases related to the immune system. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker andlor immunotherapy target for the above listed tissues.
35 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:65 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 356 of SEQ ID N0:65, b is an integer of 15 to 370, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:65, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 56 The translation product of this gene shares sequence homology with medicago saliva salt-inducible protein.
This gene is expressed primarily in human chronic synovitis.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skeletal or rheumatoid disorders, particularly, chronic synovitis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. connective tissues, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:215 as residues: Lys-30 to Ser-44, Pro-77 to His-82.
The tissue distribution in synovium indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of and as a therapeutic agent for chronic synovitis. In addition, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scieroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:66 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 973 of SEQ ID N0:66, b is an integer of 15 to 987, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:66, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 57 The translation product of this gene shares high sequence homology with the rat and mouse peroxisomal membrane proteins [gi1297437], which appears to play a crucial role in transporting proteins into the organelle. Some human genetic disorders involving peroxisome biogenesis, such as Zellweger syndrome, may be caused by genetic defects of the import machinery located in the peroxisomal membrane. When tested against fibroblast cell lines, supernatants removed from cells containing this gene activated the EGRl assay. Thus, it is likely that this gene activates fibroblast cells through a signal transduction pathway. Early growth response 1 (EGR 1 ) is a promoter associated with certain genes that induces various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation.
This gene is expressed primarily in normal human liver.
Therefore, polynucIeotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the hepatic system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic disorders and liver metabolic diseases, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. liver, cancerous and wounded tissues) or bodily fluids (e.g. lymph, bile, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression Level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:216 as residues: Lys-57 to Ser-66.
The tissue distribution in liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases relating to the liver. Furthermore, the homology indicates that the translational product of this gene may be useful in the detection and treatment of a number of disorders resulting from the improper transport of proteins into the organelle due to defects in peroxisomal membrane proteins, such as Zellweger syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:67 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1004 of SEQ ID N0:67, b is an integer of 15 to 1018, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:67, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 58 The gene encoding the disclosed cDNA is thought to reside on chromosome 4 Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4.
This gene is expressed primarily in human fetal dura mater.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include.
but are WO 99/22243 PCTlUS98/22376 not limited to, developmental or neurologic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:217 as residues: Ala-19 to Lys-34.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neurological diseases. Furthermore, the tissue distribution indicates that polynucleotides .
and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, and/or sexually-linked disorders.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:68 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 748 of SEQ ID N0:68, b is an integer of IS to 762, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:68, and where b is greater than or equal to a + 14.
WO 99/22243 PCTIUS98/2237b FEATURES OF PROTEIN ENCODED BY GENE NO: 59 The gene encoding the disclosed cDNA is thought to reside on chromosome 16.
5 Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 16.
This gene is expressed primarily in T helper cell and human uterine cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 10 biological sample and for diagnosis of diseases and conditions which include, but are not limited to, relating to hemopoietic and uterus disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and female reproductive 15 system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level. i.e., the expression level 20 in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-helper cells and uterine tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders relating to both the immune and female reproductive systems. Expression of this gene product in T-cells indicates a role in the 25 regulation of the proliferation; survival; differentiation; andlor activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, 30 the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product 35 may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:69 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 616 of SEQ ID N0:69, b is an integer of 15 to 630, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:69, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 60 This gene is expressed primarily in human fetal epithelium, and to a lesser extent, m testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental or reproductive disorders, in addition to diseases of the integumentary system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the diseases relating to the epithelium; expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
epithelium, testes, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal epithelium and testes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of epithelium related diseases. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e.
nevi, moles, WO 99/22243 PCTIUS9$122376 freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. Moreover, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Furthermore, the tissue distribution also indicates that the protein product of this gene is useful for the treatment and diagnosis of conditions concerning proper testicular function (e.g. endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence. This gene product is also useful in assays designed to identify binding agents as such agents {antagonists) are useful as male contraceptive agents.
Similarly, the protein is believed to by useful in the treatment and/or diagnosis of testicular cancer.
The testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:70. and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 926 of SEQ ID N0:70, b is an integer of 15 to 940, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:70, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 61 When tested against both U937 Myeloid cell and Jurkat T-cell cell lines, supernatants removed from cells containing this gene activated the GAS assay.
Thus, it is likely that this gene activates both T-cells and myeloid cells through the Jak-STAT
S signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT
pathway.
The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT
pathway, reflected by the binding of the GAS element, can be used to indicate proteins i0 involved in the proliferation and differentiation of cells.
This gene is expressed primarily in human adult lymph node and in early stage human lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 15 biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, lymphatitis and pulmonary disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system 20 and respiratory system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue 25 or bodily fluid from an individual not having the disorder.
The tissue distribution in adult lymph indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases relating to the immune system and respiratory system. Furthermore, expression of this gene product in lymph nodes indicates a role in the regulation of the 30 proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, 35 as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. The biological activity data supports the notion that the translation product of this gene is an activator of various cells of the immune system, and thus could play an important role in the activities of the immune system.
Many polynucieotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:71 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1089 of SEQ ID N0:71, b is an integer of 15 to 1 I03, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:71, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 62 This gene is expressed primarily in glioblastoma and anergic T-cell.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural and immune disorders, such as glioblastosis cerebri.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS and immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, neural, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders relating to the CNS and the immune system. Furthermore, expression of this gene product in T-cells indicates a role in the regulation of the proliferation; survival;
differentiation;
5 and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against 10 the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion 1 S of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available 20 and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:72 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more 25 polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 885 of SEQ ID N0:72, b is an integer of 15 to 899, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:72, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 63 One embodiment of this gene comprises polypeptides of the following amino acid sequence:
CLAEAVSVIQSIPIFNETGRFSFTLPYPVKIKVRFSFFLQIYLIMIFLGLYINFRHLY
KQRRRRYGQKKKRSTKKKDLDGFLPV (SEQ ID N0:365). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in keratinocytes and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, integumentary, or neurological and behavioural disorders.
Similarly, polypeptides. and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the nervous systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntinton's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. Alternatively, expression within keratinocytes indicates polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:73 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 535 of SEQ ID N0:73, b is an integer of 15 to 549, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:73, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 64 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
LCSTPVPTLFCPRIVLEVLV VLRSISEQCRRVSSQVTVASELRHRQWVERTLRSR
QRQNYLR (SEQ ID N0:366). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in osteoclastoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skeletal disorders, and diseases of the haemopoietic and immune system, particularly cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bones, immune and haemopoietic system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.skeletal,hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:223 as residues: Ser-59 to Glu-67.
The tissue distribution in osteoclastoma tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatement and diagnosis of disorders of the bones, immune and haemopoietic systems and cancer. Moreover, the protein may play a role as a therapeutic in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders. For example, in rheumatoid arthritis. lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:74 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 576 of SEQ ID N0:74, b is an integer of 15 to 590, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:74, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 65 When tested against dermal fibroblast cell lines, supernatants removed from cells containing this gene activated the EGR 1 (early growth response gene 1 ) promoter element. Thus, it is likely that this gene activates fibroblast cells through the EGRI
signal transduction pathway. EGR I is a separate signal transduction pathway from Jak-STAT, genes containing the EGR1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
ARGETAYDGAAVEFQEPLSSCLFSSLNPHHWPTLGVGRPVMLTLEDKD (SEQ
ID N0:367), ELLQCQMLEASTLIHLHHPRPGFPALCSFLGFRHHLHHDALCIRV
LPEDLEAKLCVSLHQLLHRGLCLPGFGAACPGDQGSEDEARPPAVLRAVALLR
AGLRHLSVHSGWYHLPH SRNGLPLLALVVHFPEYGGGPREPVPGQSG
EFGRRTELSTKGDTGDSRNSHLAQDMASLPFFKPCECTHV AVCSPPHPLCQ
YLCL (SEQ ID N0:368), LQCQMLEASTLIHLHHPRPGFPALCSFL (SEQ ID
N0:369), HQLLHRGLCLPGFGAACPGDQGSEDEARPPA (SEQ ID N0:370), andlor LALVVHFPEYGGGPREPVPGQSGEFGR (SEQ ID N0:371) .
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, male reproductive and endocrine disorders, cancer, particularly testicular cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive and endocrine systems. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, testes, endcrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:224 as residues: Lys-53 to Leu-60, Pro-94 to Gln-99, Ser-176 to Gly-184, Ser-199 to Val-207.
The tissue distribution in testes, combined with the detected EGRI biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of male reproductive and endocrine disorders, including aberrant testicular function (e.g. endocrine function, sperm maturation).
Moreover, in light of the EGR1 activity, it may also be useful in the diagnosis and treatment of a variety of proliferative disorders, especially testicular cancer. Protein, as WO 99/22243 PCT/US98/2237b well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
5 ID N0:75 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of 10 a-b, where a is any integer between 1 to 1042 of SEQ ID N0:75, b is an integer of 15 to 1056, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:75, and where b is greater than or equal to a + 14.
15 FEATURES OF PROTEIN ENCODED BY GENE NO: bb In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: QSWTAPAARLPMALPQMCDGSHLASTLRYC (SEQ ID
N0:372), QSAAQWFWWPGRSASLGGAKGMQPPSLASWPXPRSIRCL RAPAPC
ESCRTPKVVDI PTYEEAVSFPVAEGPPTPPAYPTEEALEPSGSRDALLSTQPA
WPPPSYESISLALDAVSAETTPSATRSC SGLVQTARGGS (SEQ ID N0:373), GSTGLWRGDRGPIEGGPGMLAL TDHSRVSFPVAEGPPTPPAYPTEEAL
EPSGSRDALLSSVXGASWPGWAVASPSLHQAKQSVPATRTTVPLTVM Q (SEQ
25 ID N0:374), QWFWWPGRSASLGGAKGMQPPSLASWP (SEQ ID N0:375), SSAA
VQVACCCSLACCGPSRPASQGHLRW (SEQ ID N0:376). VSFPVAEGPPTPPAYP
TEEALEPSGSRDALLS (SEQ ID N0:377), and/or RVSFPVAEGPPTPPAYPTEE
ALEPSG (SEQ ID N0:378). Polynucleotides encoding these polypeptides are also encompassed by the invention.
30 This gene is expressed primarily in pituitary gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine disorders, such as dwarfism. Similarly, polypeptides and 35 antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endocrine, immune, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in pituitary indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders of the pituitary gland and endocrine system. Moreover, considering the vital importance of the pituitary in serving as a master regulator for various endocrine glands, the protein product of this gene would also be useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g.
hyper-,hypoparathyroidism) , hypothallamus, and testes. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:76 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 916 of SEQ ID N0:76, b is an integer of 15 to 930, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:76, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 67 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
SNEILLSFPQNYYIQWLNGSLIHGLWNLASLFSNLCLFVLMPFAFFFLESEGFA
GLKKGIRARILETLVM LLLLALLILGIVWVASALIDNDAAS (SEQ ID N0:379).
Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclased cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
This gene is expressed primarily in the developing brain, liver and heart,and to a lesser extent, in cancerous tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental,neural, hepatic, or cardiopulmonary and haemopietic disorders, in addition to cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the fetal tissues and the haemopoietic and neural systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, neural, hematopoietic, hepatic, cardiovascular, pulmonary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, bile, serum, pulmponary surfactant or sputum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:226 as residues: Glu-67 to Asn-74, Glu-88 to Asn-93, Lys-95 to Ser-105, Arg-to Ala-164. Ala-204 to Arg-210, Phe-254 to Thr-262, Pro-295 to His-311.
The tissue distribution in developing brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of haemopoietic and developmental diseases and cancers. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Alternatively, the relatively specific expression of this gene product during embryogenesis indicates that it may be a key player in the proliferation, maintenance, and/or differentiation of various cell types during development. It may also act as a morphogen to control cell and tissue type specification. Because of potential roles in proliferation and differentiation, this gene product may have applications in the adult for tissue regeneration and the treatment of cancers, which include, but are not limited to the following tissues or cells: pulmonary, immune, neural, hematopoietic, or hepatic tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:77 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 4449 of SEQ ID N0:77, b is an integer of 15 to 4463, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:77, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 68 The translation product of this gene shares sequence homology with a putative yeast transmembrane protein which may play an important role in intercellular signalling, intracellular transport, or regulation of cellular homeostasis. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: PTRPVLLLAINGVTECFTFAAMSKEEVDRYNFV (SEQ ID N0:380), andlor NDKKLLFLKGFWSSLKNETPPPHFRLRMVTGVSCSGTLWCLISGV
AVTPLQSPQWG SYTECVPPTELPIAGPGASGVQASLKSRHFVSASGHT (SEQ ID
N0:381 ). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in pulmonary, immune cells, epididymus, and testis tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the reproductive organs, immune, and pulmonary systems, in addition to endothelial and epithelial tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, respiratory and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.pulmonary, immune, reproductive, testes, epididymus, endothelial, epithelial, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, seminal fluid, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:227 as residues: Arg-45 to Thr-52, Tyr-60 to Gly-66, Ala-87 to Trp-92, Leu-to Ser-115.
The tissue distribution and homology to putative transmembrane protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases of the reproductive, pulmonary and immune system. Moreover, the protein product of this gene may be useful in the diagnosis, treatment, and/or prevention of a variety of male reproductive disorders, which include.
but are not limited to, aberrant testicular function, male sterility, impotence, or related endocrine disorders. Protein may also serve a role as a contraceptive.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:78 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 777 of SEQ ID N0:78, b is an integer of 15 to 791, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:78, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 69 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
SENRIYRNGLEKMRREVTIGRSSSICLDQQVKAGNAVHHQWLKYVCWMVVVV
GGSGVGDGG NLGM (SEQ ID N0:382). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in PMA induced T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, such as inflammatory or immunodeficiency conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:228 as residues: Ser-62 to Thr-73, Phe-80 to Gln-88.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and diagnosis of immune system disorders. More specifically, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis. granulomatous disease. inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:79 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1278 of SEQ ID NO:79, b is an integer of 15 to 1292, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:79, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 70 This gene is expressed primarily in monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, which include, but are not limited to, leukemias, lymphomas, AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in monocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of S immune disorders including: leukemias, lymphomas, immunodeficiencies {e.g.
AIDS), immuno-supressive conditions (transplantation) and hematopoietic disorders. In addition this gene product may be applicable in conditions of general microbial infection, inflammation or cancer. Moreover, this gene may also be useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:80 and may have been publicly available prior to conception of the present invention.~Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1269 of SEQ ID N0:80, b is an integer of 15 to 1283, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:80, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 71 When tested against dermal fibroblast cell lines, supernatants removed from cells containing this gene activated the EGR 1 (early growth response gene 1 ) promoter element. Thus, it is likely that this gene activates fibroblast cells through the EGR1 signal transduction pathway. EGRI is a separate signal transduction pathway from Jak-STAT, genes containing the EGR1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
NWSGRRLRMWPSAALSPAVSSPALALTSPPKPLKGEVWLRWKLLGSRAVGLF
AF IALGTQSPLLHRACLPVRQSWGCSEHKAYPILRLQPDLETQVGPGHGVN
WDLRTQIRTIGELGGDGGCSE MRPLF (SEQ ID N0:383), and/or NLFSTPCKRQ
KLIKLEWTEAPNVALRCSLSCSLIPGLSPDLSSEAPEGRSVAKMEIARQQSCWL
VCI YCFRNPESTLAPGLPACEAELGLLRAQGLPHPASPARLGNTGGAWPR
SKLGSQNTN {SEQ ID N0:384), SSPALALTSPPKPLKGEVWLRWKLLG (SEQ
ID N0:385), EHKAYPIi.,RLQPDLETQVGPGHGVNWDL (SEQ ID N0:386), andlor ALRCSLSCSLIPGLSPDLSSEAPEGRSV (SEQ ID N0:387). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 11. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11.
This gene is expressed primarily in placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental anomalies, fetal deficiencies, pre-natal disorders and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, placental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:230 as residues: Gly-22 to Gly-29, Gln-37 to Ala-44.
The tissue distribution in placental tissue, combined with the detected EGR 1 biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of developmental anomalies, fetal deficiencies and pre-natal disorders. In addition it may be useful in the detection and treatment of ovarian and endometrial cancers. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:81 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 694 of SEQ ID N0:81, b is an integer of 15 to 708, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:81, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 72 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
LAPECCCGSVTYPRALVPRPCCPEPRAPLQLTLGLFSANPVNASPWGRCRSRR
GRGNLPLGHPVSTAFSSGDS (SEQ ID N0:388), and/or NTLHSKLVPSVYHSTE
KSCLV CFGMCPSIYKKMKSVLLIGTRMLLWLSHISQGPRPEAVLPRAPSP
SAAHPWLVFRKPGKRKPLGQMQKQK REGKPASGSPC (SEQ ID N0:389), YPR
ALVPRPCCPEPRAPLQLTLGLF (SEQ ID N0:390j, and/or VL~IGTRMLL
WLSHISQGPRPEAVLPR (SEQ ID N0:391 ). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
This gene is expressed primarily in infant brain, and to a lesser extent, in placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells. particularly of the developmental and neurological systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, developmental, neural, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:231 as residues: Thr-45 to Arg-50.
The tissue distribution in fetal brain and placenta indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of various developmental and neurological disorders and diseases.
The protein product of this gene is useful for the detection/treatment of neurodegenerative disease states. behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis. demyelinating diseases, peripheral neuropathies. neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages. schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or imrnunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:82 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1450 of SEQ ID N0:82, b is an integer of 15 to 1464, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:82, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 73 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
WIIVMFGKVLKIKDFMSTYSHTYTHTHMHAHTHTHTLTLSLLQNVLTLVAISDS
DK ALLIF (SEQ ID N0:392), MTLLIAEKTWRRPWPCQWGYLGAEGDRHLEG
RSLSLRHLQGAETPVLNPDLQLPSHIGKQAWSH ALGSL (SEQ ID N0:393), MSTYSHTYTHTHMHAHTHTHTLTLSLL (SEQ ID N0:394), and/or GAEGDRHLE
GRSLSLRHLQGAET (SEQ ID N0:395). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in the spleen of patients with lymphocytic leukemia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, lymphocytic leukemia and other cancers, as well as immune disorders such as AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spleen tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of lymphocytic leukemia and other cancers, as well as other immune disorders and conditions including, AIDS, arthritis, asthma and microbial infection.
Furthermore, the protein product of this gene may be useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:83 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 602 of SEQ ID N0:83, b is an integer of 15 to 616, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:83, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 74 When tested against Jurket and fibroblast cell lines, supernatants removed from cells containing this gene activated both the GAS (gamma activating sequence), and the EGR1 (early growth response gene 1) promoter elements. Thus, it is likely that this gene activates immune or fibroblast cells through the JAK-STAT and/or EGR 1 signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. EGR1 is a separate signal transduction pathway from Jak-STAT, genes containing the EGRI promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VVEPGLKASLGA
MSTLFPSLFPRVTETLWFNLDRPCVEETELQQQEQQHQAWLQSIAEKDNNLVPI
GKPASEHYDDEEEEDD EDDEDSEEDSEDDEDMQDMDEMNDYNESPDDGEVN
EVDMEGNEQDQDQWMI (SEQ ID N0:396), LFPRVTETLWFNLDRPCVEETEL
(SEQ ID N0:397), and/or YNESPDDGEVNEVDMEGNEQDQD {SEQ ID N0:398).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
The gene encoding the disclosed cDNA is believed to reside on chromosome 11.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11.
This gene is expressed primarily in cells of the immune and haemopoietic I S systems, and to a lesser extent, in several other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and haemopoietic disorders, such as multiple myeloma, immunodeficiencies, and inflammatory conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and haemopoietic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.> cancerous and wounded tissues) or bodily fluids (e.g.lymph.
serum, plasma, urine; synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:233 as residues: Pro-21 to Gly-30.
The tissue distribution in immune tissues and cells, combined with the detected GAS and EGR1 biological acitivity indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune, haemopoietic, and integumentary systems. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lyrnphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:84 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 914 of SEQ ID N0:84, b is an integer of 15 to 928, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:84, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED. BY GENE NO: 75 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: MGFDIHGVLGEAVAEPREKKQE RAKWAPHDYDDPSLS
LQDLLISWMISTWLIPMWKCQATIWFSLIQRLLNAYCMPGNFRHWEIAANTTN
KT PGLMDFKFL (SEQ ID N0:399), EPREKKQERAKWAPHDYDDPSLSLQDL
(SEQ ID N0:400), and/or MPGNFRHWEIAANTTNKT PGLMDF (SEQ ID N0:401).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
The gene encoding the disclosed cDNA is believed to reside on the X
chromosome.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for the X chromosome.
This gene is expressed primarily in fetal liver and spleen, and to a lesser extent, in prostate cancer and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental, reproductive, immune, and haemopoietic disorders Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and developing systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, hepatic, reproductive, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, bile, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in developing and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders of the haemopoietic and developing immune systems.
In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution.
radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in iymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
Moreover, the expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. The protein may also show utility in the treatment or diagnosis of various hepatic or reproductive disorders, which include, but are not limited to hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells, and prostate cancer, and/or congenital defects such as X-linked conditions. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Sorne of these sequences are related to SEQ
ID N0:85 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 709 of SEQ ID N0:85, b is an integer of 15 to 723, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:85, and where b is greater than or equal to a + 14 FEATURES OF PROTEIN ENCODED BY GENE NO: 76 This gene is expressed primarily in fetal spleen and Wilm's tumor.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, haemopoietic, immune, developmental, or renal disorders, such as congenital defects, mutliple myeloma, or Wilm's tumor. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the haemopoietic and developing systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, immune, hematopoietic, renal, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the haemopoietic and developing systems and cancer. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukenua since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. The expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:86 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 556 of SEQ ID N0:86, b is an integer of 15 to 570, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:86, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 77 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the (gamma activating sequence ~ promoter element. Thus.
it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in induced T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and inflammatory diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids {e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune and inflammatory diseases.
The secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferationldifferentiation modulating activity or induction of other cytokines;
immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy);
regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy);
stimulation or growth of bone, cartilage, tendons, ligaments andlor nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone {for control of fertility);
chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases;
for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:87 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 625 of SEQ ID N0:87, b is an integer of 15 to 639, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:87, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 78 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: QSVPSPPLAPPLPPSLPSFLFTETRSHYVARLVSNSWAQM
ILLPWPLKVLGLDVSHCAWPKSVFLQAMEEIADFCLFSVKYQVSSMTCF DRT
SYMKNTYL (SEQ ID N0:402), and/or LFTETRSHYVARLVSNSWAQMILLPWP
(SEQ ID N0:403). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in bone marrow.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. anemias (leukemias), immune deficiencies and other hematopoietic-related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune. hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in bone marrow indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of hematopoietic and immune disorders, which include, but are not limited to the following: leukemias, lymphomas, auto-immunities, immunodeficiencies (e.g.
AIDS), immuno-supressive conditions (transplantation) and other hematopoeitic disorders, such as multiple myeloma. In addition this gene product may be applicable in conditions of general microbial infection, inflammation or cancer. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:88 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 694 of SEQ ID N0:88, b is an integer of 15 to 708, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:88, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 79 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
SQIKSEKKHIGKAYTCTQTQSTGMQSTLTI V AKKKSRNHTESYTRKKQENQIV
LIPWHQKKHPEGTHTCSHSLRRDTNTAADTQRKIRAHRYTYRRDKYSDTLVTH
DHYKGDKHPSNTHTQPR XEFLQPGGSTNSRAAAPRXSSSFCPFS EGYS
SWGYH (SEQ ID NO:404),GMQSTLTIVAKKKSRNHTESYTRKKQ (SEQ ID
N0:405), KKHPEGTHTCSHSLRRDTNTAADT (SEQ ID N0:406), and/or RRDKY
SDTLVTHDHYKGDKHPSNT (SEQ ID N0:407). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, such as leukemias, lymphomas, AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:238 as residues: Asp-38 to Leu-43.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders including leukemias, lymphomas, AIDS, arthritis and asthma, as well as other conditions which potentially implicate the immune system, such as atherosclerosis, cancer and infection. In addition, This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity: immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:89 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 935 of SEQ ID NO:89, b is an integer of 15 to 949, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:89, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 80 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KHLPLKAPIDLDNKNSCMFCSRDIFCRFH HSTAWLFL
GRTTDRILGLHHYLIRYQFEIENLCLMKIVIPV VSMKTNCQFDFLGQLKQNLYH
(SEQ ID N0:408), APIDLDNKNSCMFCSRDIFCR (SEQ ID N0:410), and/or IENLCLMKIVIPVVSMKTNCQFDFLGQL (SEQ ID N0:409). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in prostate carcinoma cell line stimulated with 30 nM synthetic androgen, 81881 cells and, to a lesser extent, in activated monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. reproductive or immune disorders, particularly prostate cancer and prostate ailments. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in the prostate indicates that polynucleotides and polypeptides corresponding to this gene are useful for the disgnosis and intervention of prostate cancer and prostate ailments, or related proliferative conditions in either said tissue or other tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:90 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1157 of SEQ ID N0:90, b is an integer of 15 to 1171, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:90, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 81 The translation product of this gene shares strong sequence homology with human protocadherin 42 (GenBank accession no. gi1387675), PCDH7 (BH-Pcdh)a, and its associated isoforms PCDH7 (BH-Pcdh)b, and PCDH7 (BH-Pcdh)c which are thought to be important in tissue and cell-cell adhesion, repair and development (See Genbank Accession Nos.gnlIPIDId1026122 (AB006755), gnIIPIDId1026123 (AB006756), and gnlIPIDId1026124 (AB006757)). The polynucleotides encoding this gene have been gened by another group subsequent to our filing {See Yoshida K, et al, Genomics 1998 May 1;49(3):458-61, which is hereby incorporated by reference).
The cytoplasmic domain of cadherin interacts with the cytoskeleton through catenins and other cytoskeleton associated proteins. The cytoplasmic domain is not present in all cadherins, but in those which possess it, it is essential for the cadherins adhesive function. The cadherins which do not possess a cytoplasmic domain appear to function via a different method from those with a cytoplasmic domain. This protein sequence is involved in cell-cell adhesion. This sequence may have regulatory functions in the cell, as well as the cell-cell adhesive properties. Antibodies produced against this sequence are useful for modulating the binding activity of protocadherins, and can be used therapeutically. BH-Pcdh has an extracellular domain consisting of seven repeats of the cadherin motif (EC 1 to 7). EC2 of BH-Pcdh is unique in having a 55-amino-acid insertion in the middle of the motif. There are three isoforms of BH-Pcdh, denoted -a, b, and -c, which have different cytoplasmic tails and a 47-amino-acid deletion in the EC2-3 region of BH-Pcdh-c. While only a 9.0-kb message was detected in normal tissues, 4.5- and 9.0-kb mRNA species were seen in the human lung carcinoma cell line A549. Furthermore, only the 4.5-kb mRNA was detected in HeLa cell S3 and WO 99122243 PCT/US98/2237b human gastric cancer cell lines MKN28 and KATO-III. Southern blot analysis indicated that the BH-Pcdh gene is likely to be conserved among various vertebrates. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GTSVNESVSNATAIDSQIARSLHIPLTQDIAGDPSYEISKQRLSIVIGVVAGI (SEQ
ID NO:411), PKIKMAMKPAKKITKTFLHPNSMTNLKSLKRTRKTKNLSSLSTA
ALSLWRLLSQMDRGMIVSMRSCQTAQ AWGDTGPLMVGPAVLTWQGITNL
VPHCLLFSFIPSHQLQEKNTRPYKIYHQPTHLWEQETTFQLDQITAL STAVKP
ITSTANRCVYIHTLLCLAEFHSNMMLHYAPYCDDLSTPKPAGACPWPWGVSQS
LLVPLVVHFIF ESFSFSYTEK (SEQ ID N0:412), CSIMHHTVMTFLLRNLLEPA
LGRGVSANHCLFHLLYILFL SLFLSHIQKNSMKIK (SEQ ID N0:413), TAIDS
QIARSLHIPLTQDIAGDPSYEISK (SEQ ID N0:414), YCRSKNKNGYEAGKKDH
EDFF (SEQ ID N0:415), GPGSPDLARHYKSSSPLPTVQ (SEQ ID N0:416), and/or LPPANTFVGAGDNISIGSDHCSEYS (SEQ ID N0:417). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 4. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4.
This gene is expressed primarily in ovarian tumor, and to a lesser extent in, striatum and HL-60 cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer and reproductive dysfunction, in addition to cardiovascular and neural disorders,such as atherosclerosis, and neurodegenerative disorders, such as Alzheimer's and Parkinson's, or other disorders resulting from aberrant cell-adhesion.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive, nervous and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, neural, cardiovascular, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:240 as residues: Tyr-15 to Leu-59, Ala-68 to Asp-85, Pro-87 to Asn-96, His-to Lys-129, Ser-153 to Gln-170.
The tissue distribution in ovarian and muscle tissue, combined with the strong homology to various cadherins indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, study and treatment of various neoplastic disorders such as squamous cell carcinomas and related tumors, and nervous system and reproductive disorders. Considering the vital importance of cell-adhesion amongst various cellular functions, in particular chemotaxis by the immune and hematopoietic cells indicates that this gene product may play a direct, or in-direct role in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Furthermore, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also play an in-direct role in the regulation of a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines;
immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy);
regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy);
stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility);
chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases;
for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:91 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucieotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1137 of SEQ ID N0:91, b is an integer of 15 to 1151, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:91, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 82 The translation product of this gene shares sequence homology with the G-protein coupled receptor TM3 consensus polypeptide which may implicate an important function for this protein in various signal transduction pathways. G-protein coupled receptors are known to have a variety of functions including modulating immune system tissue through interaction with cytokines and lymphokines. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GTSNAS VSPTICICMCGYVHIWFFICLCVYLKVLQGSACPWIAAAV VMRRMRK
VQEKGEVFRNMAATWAL RSGIQSLNSLVSSAFFTIFMTLGSSWNLIVSLSSLV
NWTGLFSFYFSRN (SEQ ID N0:418), CLCVYLKVLQGSACPWIAAAVV
MRRMRK (SEQ ID N0:419), and/or TIFMTLGSSWNLIVSLSSLVNWTGLF (SEQ
ID N0:420). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in breast lymph node.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, breast cancer, or other immune or reproductive disorders and diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, breast, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, breast milk, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:241 as residues: Cys-34 to Gly-48.
The tissue distribution in breast lymph nodes and homology to a conserved G-protein coupled receptor TM3 consensus sequence indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for breast cancer or immune diseases. Considering the vast roles which G-protein coupled receptors play in the maintenance of important cellular fuctions, the secreted protein may have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines;
immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy);
regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy);
stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility);
chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity {e.g. for treating septic shock, Crohn's disease}; as antimicrobials; for treating psoriasis or other hyperproliferative diseases;
for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Furthermore, the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements.Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:92 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 700 of SEQ ID NO:92, b is an integer of 15 to 714, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:92, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 83 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
QPDIPVLPVGFSQNCSFKVSGCWKGGLIAEKVGTLGTPKGRR AWPETEF
FRFLEPGLP (SEQ ID N0:421), and/or RGFRMAQPLVNTFQVAVPVEDL
APQQNPSRFPADPALLSFLTG SILAPGKVIWVNVSFTAIIWPTWDSMAI
GELTIASHASMTLHIGRPGSRKRKNSVSGHARLPFGVPSVPT FSAISPP
FQQPETLKEQF (SEQ ID N0:422), EDLAPQQNPSRFPADPALLSFLTG (SEQ ID
N0:423), and/or TWDSMAIGELTIASHASMTLH1GRPGSRK (SEQ ID N0:424).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in activated T-cells, hepatocellular tumor, pancreas islet cell tumors, and hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hepatic, and endocrine disorders, such as cancers, particularly of T-cells, hepatocellular tumors and pancreas islet cell tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hepatic, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, bile, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:242 as residues: Glu-43 to Lys-50, Ser-53 to Phe-60.
The tissue distribution in T-cells, hepatocellular tumors, and pancreatic islet cell tumors indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of immune, hepatic, and endocrine disorders, and other cancer types. Expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders in various tissues, aside from those disclosed above. Similarly, developmental tissues rely on decisions involving cell differentiation andlor apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:93 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 796 of SEQ ID N0:93, b is an integer of 15 to 810, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:93, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 84 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
VSPQLMGIKREPSAAQLSVGEEHTLDREGRELVDLPGQPSQKIKIKNKSSLHPG
LAPP AHYKTATTTNLF (SEQ ID N0:425), and/or PSAAQLSVGEEHTLDREGREL
(SEQ ID N0:426). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in hepatocellular tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hepatic disorders, such as liver diseases and hepatocellular tumor, including proliferative disorders in other tissues and cell types. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.hepatic, proliferating, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, bile, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in hepatocellular tumor tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of hepatocellular tumor or other liver disorders.
Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:94 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1162 of SEQ ID N0:94, b is an integer of 15 to 1176, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:94, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 85 When tested against reh cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus. it is likely that this gene activates B-cells through the JAK-STAT signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: NCDHDFIQPLHTPMSAL FQSEFS (SEQ ID N0:427), SILNM
GLFTEQRPWPAAARCARQSTVAGAIRRARGTVTMWQVAGAAW ASPDRRAKV
HPCRHAAPCLPSPCRRGLQMSGPLQATRGRVTLRSHQVGCKRATGSTENSL
(SEQ ID N0:428), QKSKGSPLQTCCSLPTLPMQERPADEWSTPGDQGKSYIK
KPPGGLQKGHRLHRKLTLKQGRHRGVE GLNEIMVTVLKEEFPVSKPGLNV
LPTFHRHHECYQHGMNLTARISVVS {SEQ ID N0:429), ARQSTVAGAIRR
ARGTVTMWQVAGA (SEQ ID N0:430), PCRRGLQMSGPLQATRGRVTLRSHQ
(SEQ ID N0:431 ), LPMQERPADEWSTPGDQGKSYIKKPP (SEQ ID N0:432), and/or NVLPTFHRHHECYQHGMNLTARI (SEQ ID N0:433). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human fetal kidney, adult testis, T-cell lymphoma, and a fetal liver/spleen cDNA library.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, renal, developmental, reproductive, immune, or hematopoietic disorders, particularly kidney disease, lymphoma, congenital defects, multiple myeloma, SCID, male sterility, and cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the kidney and immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoeitic, reproductive, renal, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:244 as residues: Gly-35 to Gly-40.
WO 99122243 PCT/US98l22376 The tissue distribution in fetal kidney and T-cells, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatement of kidney diseases or immune disorders, especially cancers. Specifically, this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
Similarly, developmental tissues rely on decisions involving cell differentiation andlor apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:95 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To Iist every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1014 of SEQ ID N0:95, b is an integer of 15 to 1028, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:95, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 86 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in breast, human embryo, and chronic spleen lymphocytic leukemia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, developmental, hematopoietic or immune disorders, such as breast cancer, congenital birth defects, or leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast or hematopoietic systems, expression of this gene at significantly higher or lower levels may be detected in certain IS tissues or cell types (e.g.reproductive, immune, hematopoietic, developmental, breast, and cancerous and wounded tissues) or bodily fluids {e.g.lymph, amniotic fluid, breast milk, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:245 as residues: His-2 to Asn-$, Gln-35 to Phe-44.
The tissue distribution in breast and lymphocytic leukemia cells, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or intervention of breast cancer, leukemia or other hematopoietic related disorders. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies WO 99/22243 PCT/US9$/22376 directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:96 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 733 of SEQ ID N0:96, b is an integer of 15 to 74?, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:96, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 87 This gene is expressed primarily in brain containing medulla blastoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, particularly specific brain tumors such as medulla blastoma, as well as other diseases and conditions of the brain. such as schizophrenia, Alzheimer's disease, Tourette's syndrome, Parkinson's disease, Huntington's disease.
mania, dementia, paranoia, depressive and addictive predispositions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of specific brain tumors such as medulla blastoma. In addition it may also be useful for the diagnosis and treatment of developmental, degenerative and behavioral conditions of the WO 99122243 PCT/US9$/2Z376 brain and nervous system, such as schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, mania, dementia, paranoia, addictive behavior, obsessive-compulsive and sleep disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:97 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 614 of SEQ ID N0:97, b is an integer of 15 to 628, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:97, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 88 When tested against Jurket cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates T-cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: INVLYCSRDSLMGRTIMESSDYIKKGANVSPVLGVRQQ AV
(SEQ ID N0:434). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adrenal gland tumor and T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the endocrine and immune or haemopoietic systems, particularly inflammatory or immunodeficiency conditions. such as AIDS.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and endocrine systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types {e.g.immune, hematopoietic, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells and adrenal gland tissues, combined with the detected GAS biological activitiy indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune and endocrine systems and cancer. Moreover, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities.
Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotaetic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:98 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 890 of SEQ ID N0:98, b is an integer of 15 to 904, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:98, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 89 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: SLLMYFVFKIFFQSLCVLGYCILPLTVA (SEQ ID N0:435).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a IS biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:248 as residues: Thr-43 to Thr-48.
The tissue distribution in dendritic cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune system disorders. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stern cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:99 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 562 of SEQ ID N0:99, b is an integer of I 5 to 576, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:99, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 90 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
RLWMTKAHPALRHLLLLFTLALTLLAQGCCAVAPSGCADLAGFCSLGHS C
(SEQ ID N0:436). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human stomach.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, digestive and gastrointestinal conditions, particularly ulcers and cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.gastrointestinal, metabolic, mucosal, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, chyme, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:249 as residues: Pro-32 to Gly-38.
S The tissue distribution in stomach tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of gastrointestinal disorders, or other disorders afflicting mucosal or endothelial tissues.
Protein, as well as, antibodies directed against the protein rnay show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:100 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 699 of SEQ ID NO:100, b is an integer of 15 to 713, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:100, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 91 The translation product of this gene was found to have homology to the conserved K07F5.14 protein from Caenorhabditis elegans (See Genbank Accession No gnllPIDle233697) which may be important in regulation of important cellular functions, including homeostasis and cell division. When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) pathway. Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
RTCTPWMGFWCLVCSLFAPVPTSRKYLVSKPGCYQRRRV FGVCFTKPL (SEQ
ID N0:437), WLLSEKKG (SEQ ID N0:438), and/or GVFYKAAVIG (SEQ ID
N0:439). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in bone marrow and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune or hematopoietic disorders, particularly multiple myeloma, immunodeficiencies, and cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and endocrine systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in bone marrow and T-cells, combined with the detected GAS biological activity in U937 cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of immune and hormonal disorders and neoplasias. Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Moreover, the protein may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoirnmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation andlor proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:101 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of I S a-b, where a is any integer between I to 635 of SEQ ID NO: l0 i , b is an integer of 15 to 649, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:101, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 92 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
CKTSPLPKEGQSAVSVPVSSHFLAHSAPLSGGHAHVFARDGATGL (SEQ ID
N0:440), LGRGSGERKTPVSCFAQISKSRGGRSKSLTHLCTHTHTQVTEL
DVRMSHGCLRXQHAGRLAPPPPLRFCL TACWGRRGEAETVWKDPASSQ
HPPPSEKPHRQDRHPERWHQPGGPIPGKHMRVSPGQRGRVCQEMGRNRN
(SEQ ID N0:441 ), FCLRDFKIWRGRLEAGRTEGRL AGERFGGEEDPSFLFC
SDFKVEGWAFEISHSLVHTHTHTGHGAGRADVTRVPAGTARWEAGSPTPSPV
LF DSLLGAAGRG (SEQ ID N0:442), AQISKSRGGRSKSLTHLCTHTHTQVTEL
(SEQ ID N0:443), EKPHRQDRHPERWHQPGGPIPGKHMR (SEQ ID N0:444), GRLEAGRTEGRL AGERFGGEEDPSFL (SEQ ID N0:445), and/or VTRVPAGTARWEAGSPTPSPVLF (SEQ ID N0:446). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 19. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.
This gene is expressed primarily in ovary, spinal cord, and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental, reproductive, and neurological conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nrevous and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, reproductive, ovarian, immune, hematopoeitic, and cancerous and wounded tissues) or bodily fluids (e.g.Iymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily 1 S fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:251 as residues: Pro-34 to Pro-53.
The tissue distribution in spinal cord and fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of neural, hematopoietic, and developmental disorders.
Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition. homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia. pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include, but are not limited to bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:102 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 683 of SEQ ID N0:102, b is an integer of 15 to 69?, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:102, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 93 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: DEGVQGERLFRILRINGEKPYNFVDYFHCEY (SEQ ID
N0:447), KVVRIDNGILCSHKKTEIMSLQQHGWIWRPYLKQTNTGTENQIPHTL
TYKWELNFEYIXTQXRGXXDSEAYLKVEGGRREGIQKLPIRYYVYYLGDKIICT
SSSCSMHLLM (SEQ ID N0:448), HKDTCMSMFT AALFTIAKTWN (SEQ ID
N0:449), MPINDRLDFKRWYV (SEQ ID N0:450), TMESYVAIKRQRSCPCSNM
VGSGGHILSKLTQEQKTKYHILS LISGS (SEQ ID N0:45 I ), EIMSLQQHGWIW
RPYLKQTNTGTEN (SEQ ID N0:452), and/or RREGIQKLPIRYYVYYLGDKIICT
(SEQ ID N0:453). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in bladder tissue from a human male.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, gastrointestinal, urogenital, and nephrotic conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal and excretory systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.renal, bladder, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the. standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:252 as residues: Arg-52 to Ala-57, Pro-66 to Thr-72.
The tissue distribution in bladder tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of gastrointestinal and urinary tract disorders.Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:103 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1274 of SEQ ID N0:103, b is an integer of 15 to 1288, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:103, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 94 This gene is expressed primarily in bladder tissue from a human male.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, gastrointestinal, renal, and urinary tract conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the intestinal and urinary tract, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.renal, urogenital, bladder, cancerous and wounded tissues) or bodily fluids (e.g.Iymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in bladder tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of urinary tract and gastrointestinal disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:104 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1013 of SEQ ID N0:104, b is an integer of 15 to 1027, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:104, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 95 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: LHGEQVPI YIFLLMQPLNFECISFLNCIEQYSVGVI HNSV
TIYACDREENCMDIRYL (SEQ ID N0:454), and/or GTSWASRFFTCH (SEQ ID
N0:455). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and inflammatory disorders, particularly immunodeficiencies such as AIDS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:254 as residues: Lys-28 to Thr-34.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune system. Moreover, This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease. inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:105 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 696 of SEQ ID N0:105, b is an integer of 15 to 710, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:105, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 96 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GPPRXFXPKKAILGXPPXGR VPPFRYRSRNSRGRPHXSAPRV RFCLENS WLR
(SEQ ID N0:456), andlor PLNTMMCMMCKMKVSPKIFSKLKRKYLNSNTLTKL
EMQTVHLESSLASCSPNKSGXVGRTR GVDPGNSGTGT (SEQ ID N0:457).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This Gene is expressed primarily in lymphoma and frontal cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are 1 S not limited to, neurological and haemopoietic diseases, particularly neurodegenerative conditions such as Alzheimers and Parkinsons. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in frontal cortex and lymphoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases of the neural and haemopoietic systems.
Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment S and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
Moreover, the expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Since, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation, this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:106 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 516 of SEQ ID N0:106, b is an integer of I ~
to 530, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:106, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 97 This gene is expressed primarily in the spleen of a patient with metastatic melanoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune or hematopoietic disorders, particularly metastatic melanoma and other cancers. as well as immune disorders and conditions such as anemias, AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:256 as residues: Pro-26 to Asn-34.
The tissue distribution in spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of metastatic melanomas and other cancers, as well as other immune disorders and conditions including leukemias, lymphomas, AIDS, arthritis, asthma and microbial infection.
Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, or thrombocytopenia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:107 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 378 of SEQ ID N0:107, b is an integer of 15 to 392, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:107, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 98 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: GTVTQKRK CVFGKYLLSTCSLMFSSMHGACSWKA
KQTSSSAGFLCLHVLCPALQLTREKYKTWPWPSFI (SEQ ID N0:458), and/or MKEGQGHVLYF SRVNCKAGHXTCRQRKPADELVCFAFQEQAPCILLNI
RLQVLNKYLPNTHFLFCVTVP (SEQ ID N0:459). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 8. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 8.
This gene is expressed primarily in pineal gland and synovial sarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine or skeletal disorders, including cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endocrine, pineal, skeletal, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in pineal gland indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the endocrine system. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes. Alternatively, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:108 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 977 of SEQ ID N0:108, b is an integer of 15 to 991, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:108, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 99 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
TMTGIDSSPEEILRQVGCKQQQGKGVEHVEGSSAEAGEAARGGGAK GGGG
AAGKGTSKVGTLRRTRGST (SEQ ID N0:460). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in breast and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the reproductive system and developing organs, particularly congenital defects afflicting the immune or hematopoietic system, such as immunodeficiencies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, developing, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:258 as residues: Gly-23 to Asn-30, Ser-37 to Asn-43.
The tissue distribution in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases involving developmental tissues and reproductive organs. The secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments andlor nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease}; as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:109 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 898 of SEQ ID N0:109, b is an integer of 15 to 912, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:109, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 100 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
AQREAGSRPRRRKSLKAVAMLXVEMGGGCRGSMGPGPGYSAGSRVCRGSSL
PQVAPFNPSRAHLLPPPVG GGLNSVWLSGVQLSTPPYADWEGVGQSPQ
PRGPWMGSSSLGTVGPGCVLSGCPTVKANGGSPCSEMLGER RLLEPSVG
PVSGCPERREGGHGARGAAGVVVKGHASVQLNFLSLI (SEQ ID N0:461), KAEFTFAKEKNAKAQLGKKGTRW V KHDKRKEIQLYGCVTLNDDPSCPPCPVP
TLPPFWTA TYGSHGRFQKPPFSQHLRAGGAPVGLDCGAPTQYAARPHGPK
(SEQ ID N0:462), GCRGSMGPGPGYSAGSRVCRGSSLPQ (SEQ ID N0:463), QPRGPWMGSSSLGTVGPGCVLS (SEQ ID N0:464), and/or GAAGVVVKGH
ASVQLNFLSLI (SEQ ID N0:465). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in endothelial, immune, and cancer cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases involving immune, endothelial, and haemopoietic tissues or cells, particularly cancers, inflammatory or immunodeficiency conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, haemopoietic and endothelial systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endothelial, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune and hematopoietic tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders of the immune and haemopoietic systems, including cancer.
More specifically, this gene product may be involved in the regulatic.~~ of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic Lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:110 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 861 of SEQ ID NO:110, b is an integer of 15 to 875, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:110, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 101 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: GKPLSAIFPICH MMFLPGKFNLGISHRCCRMT SPWDK
RQQLRQECKSDPHVQNPRIHFPESKNSFPSAYIFVSEGNGVSPSK WHCIY
SGTSLSH (SEQ ID N0:466), andlor GERGRYQSKYSATWMVTPHYLQTQRC
KLREMNSWIQGNEFLDSEHEGQIYIPVSIVDAYPKD (SEQ ID N0:467).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human kidney, and to a lesser extent, in liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, kidney, urogenital, hepatic, and endocrine disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal or endocrine systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.urogenital, kidney, endocrine, hepatic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, bile, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:260 as residues: Glu-38 to Lys-43.
The tissue distribution in kidney indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of renal disorders, including noninflammatory and inflammatory lesions, and tumors of the kidney.
Moreover,this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Alternatively, expression within liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g.
hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:111 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 445 of SEQ ID NO:11 l, b is an integer of 15 to 459, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: I 11, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 102 This gene is expressed primarily in kidney cortex and fetal tissue.utility_ The tissue distribution in kidney indicates that this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:112 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 595 of SEQ ID N0:112, b is an integer of 15 to 609, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:112, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 103 This gene is expressed primarily in ovary and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive and neurological conditions, particularly proliferative S disorders, such as ovarian cysts or cancer, in addition to neurodegenerative conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, reproductive, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine. synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in ovarian tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of reproductive disorders, such as infertility. Alternatively, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors; including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders; or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO: l I3 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1390 of SEQ ID N0:113, b is an integer of 15 to 1404, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:113, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 104 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ISIRGRIL
YKMAYFKVCVIIWFQQFCVEETSIIKNVRMLTSEFQNSYATPVSGLLPGAVAWR
GGAVYGWVRHAMQVLQ KEPTQPSSFLPPSDAASFWGPESRLHLTW (SEQ ID
N0:468), KPFAFSARNFPTMLSEAYFQDPRMRQHHLGVERMTV AWVPSAIP
AWRASPTRTQHHPSKPQHQEGAQKQGWHMNSGILMSAYEHFL (SEQ ID
N0:469), and/or HSKQNICREVNILKMFLHEIKKTVTDNISTQRRFTYNHQPGS
VSIFSVTDILDFEVPFGL (SEQ ID N0:470). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in melanocytes, and PHA stimulated T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not Iiznited to, immune or integumentary system disorders, and cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.integumentary, immune, hematopoieitc, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, diagnosis and treatment of cancers and immune system disorders. Alernatively. the expression in melanocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:114 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 839 of SEQ ID N0:114, b is an integer of 15 to 853, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:114, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 105 This gene is expressed primarily in B cell lymphoma, and to a lesser. extent, in dermal fibrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or integumentary disorders, particularly lymphatic and soft tissue cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in B-cell lymphoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeftciency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Alternatively, the protein product of this gene may also be useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e.
keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erytherriatosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie.
spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:115 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 831 of SEQ ID N0:115, b is an integer of 15 to 845, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:115, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 106 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
KVIDVIFSLPPGRKATFSCPLAPLSGAXGLPGGGANRPGPFLPCIQPWGPLRLP
EGC (SEQ ID N0:471), MSSSLCPQGGKPPSLAPWPLCQGPXVCRVGVPT
GLALSSPASSHGGLCDCRKVAWLVPGPAQARG RAAWFYFYLTLFSVL (SEQ
ID N0:472), and/or LALSSPASSHGGLCDCRKVAWLVPGP (SEQ ID NO:473).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T cells, fetal liver, and to a lesser extent, in various normal and transformed tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hematopoietic, or developmental disorders, including immunodeficiencies and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:265 as residues: Arg-5 to Pro-12.
The tissue distribution in B-cells and fetal liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of immune and developmental disorders. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. In addition, expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:116 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 746 of SEQ ID N0:116, b is an integer of 15 to 760, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:116, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 107 One embodiment of this gene comprises the following amino acid sequence:
MQRERWARPWMASTVESRMPEGKWRRFSTDLATWGATPARSWTKASRGSTT
AWTRLPMRSTMVLDKQERKQRSLAMGSTTLLDRPGRKQTKRSKGSTLGSTRL
GRKQRNLAKGSTMLLTRLERXWRSLAQVPTMLLARPGRSCRMLIMGSTKPAR
RPTSC (SEQ ID N0:474 ). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in keratinocytes and tissues undergoing wound healing, and to a lesser extent, in osteoblasts and smooth muscle.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skin disorders; fibrosis; scarring; osteoporosis;
osteopetrosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skin, bone, or connective tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. skin, bone, connective tissues, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:266 as residues: Gly-76 to Leu-83, Ala-108 to Glu-113, Ala-126 to Lys-132, Gly-145 to Leu-151.
The tissue distribution in keratinocytes indicates that polynucleotides and polypeptides con esponding to this gene are useful for the diagnosis and/or treatment of a variety of skin disorders. Elevated expression of this protein in skin and keratinocytes suggest that it may be involved in keratinocyte proliferation, survival, and/or differentiation. Thus, it may play a role in such processes as fibrosis and wound healing. Similarly, expression of this protein in osteoblasts indicates that it may also play a role in osteoblast survival, proliferation, and/or differentiation, and that it may be useful in the treatment of such disorders as osteoporosis or osteopetrosis.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:117 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more poiynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 974 of SEQ ID N0:117, b is an integer of 15 to 988, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:117, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 108 The translation sequence of this gene shares homology with a mouse camodulin binding protein. The calcium-binding regulatory protein calmodulin is an essential subunit of the erythrocyte and other plasma membrane calcium ATPases. A rise in cytosolic calcium induces the binding of calcium ions to calmodulin, which triggers an allosteric activation of the calcium ATPase, and subsequently an export of calcium ions from the cell is accelerated.
This gene is expressed primarily in teratocarcinoma cells, and to a lesser extent, in myeloid progenitor cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental defects, calcium-transport defects, in addition to immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of embryonic and fetal tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
developing tissues, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:267 as residues: Tyr-124 to Gly-129.
The tissue distribution in teratocarcinoma cells indicates that polynucleotides and polypeptides corresponding to this gene are useful far the diagnosis and treatment of developmental defects as well as for organ regeneration. Moreover, expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Alternatively, the homology of the translation product of this gene to a mouse calmodulin binding protein indicates that the translation product of this gene may be useful for disorders involving calcium transport across the plasma membrane, for example. It has further been suggested this type of disorder may be responsible for disorders such as hypertension.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:118 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1933 of SEQ ID N0:118, b is an integer of 1 S
to 1947, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:118, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 109 One embodiment of this gene comprises polypeptides of the following amino acid sequence:
MRPLLGLLLVFAGCTFALYLLSTRLPRGRRLGSTEEAGGRSLWFPSDLAELREL
SEVLREYRKEHQAYVFLLFCGAYLYKQGFAIPGSSFLNVLAGALFGPWLGLLL
CCVLTS VGATCCYLLSSIFGKQLV VSYFPDKV ALLQRKVEENRNSLFFFLLFLR
LFPMTPNWFLNLSAPILNIPIVQFFFSVLIGLI PYNFICVQTGSILSTLTSLDA
1S LFSWDTVFKLLAIAMVALIPGTLIKKFSQKHLQLNETSTANHIHSRKDT (SEQ ID
N0:47S). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in ovarian tumor, and to a lesser extent, in smooth muscle and breast cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and fox diagnosis of diseases and conditions which include, but are not limited to, cancers, particularly of the ovary, musculature, and breast, such as rhabdomyosarcomas or fibroids. Similarly, polypeptides and antibodies directed to 2S these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
ovaries, breast. cancerous and wounded tissues} or bodily fluids (e.g.lymph, serum, breast milk, plasma, urine, synovial fluid and spinal fluid} or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
3S N0:268 as residues: Arg-24 to Arg-29.
The tissue distribution in ovarian tumor tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer, particularly ovarian and breast cancers. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:119 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1434 of SEQ ID N0:119, b is an integer of 15 to 1448, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:119, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 110 The translation product of this gene shares sequence homology with bovine acrosin inhibitors IIa and IIb which is thought to be important as protease inhibitors.
This gene is expressed primarily in keratinocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, integumentary disorders, such as psoriasis, and wound healing abberations. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the integumental system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:269 as residues: Tyr-39 to Lys-58.
The tissue distribution in keratinocytes, combined with the homology to the bovine acrosin inhibitors IIa and IIb indicates that polynucleotides and polypeptides corresponding to this gene are useful for the acceleration of wound healing.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:120 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 482 of SEQ ID N0:120, b is an integer of 15 to 496, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:12U, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 111 This gene is expressed primarily in fetal liver/spleen, T cells, and to a lesser extent, in bone marrow and primary dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hematopoietic disorders; immune dysfunction; lymphomas.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ 117 N0:270 as residues: Glu-28 to His-34.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of hematopoietic disorders. This gene product is primarily expressed in hematopoietic cells 164.
and tissues, suggesting that it plays a role in the survival, proliferation, and/or differentiation of hematopoieitic lineages. This is particularly supported by the expression of this gene product in fetal liver and bone marrow, the two primary sites of definitive hematopoiesis. Expression of this gene product in T cells and primary dendritic cells also strongly indicates a role for this protein in immune function and immune surveillance. Furthermore, since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO: I21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1160 of SEQ ID N0:121, b is an integer of 15 to I 174, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:121, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 112 The gene encoding the disclosed cDNA is thought to reside on chromosome 14.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 14.
This gene is expressed primarily in fetal liver, spleen, and to a lesser extent in melanocyte.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. developmental, integumentary, or hematopoeitic disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing imtnunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of fetal and embryonic tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:271 as residues: Met-1 to Met-7, Gln-43 to Glu-50, Thr-89 to Thr-95.
The tissue distribution in fetal liver and spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of developmental hematopoeitic disorders. Additionally, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of hematopoietic disorders. This gene product is primarily expressed in hematopoietic cells and tissues, suggesting that it plays a role in the survival, proliferation, and/or differentiation of hematopoieitic lineages.
This is particularly supported by the expression of this gene product in fetal liver, which is a primary sites of definitive hematopoiesis, and strongly suggesting a role for this protein in immune function and inunune surveillance.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:122 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1032 of SEQ ID N0:122, b is an integer of I S
to 1046, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:122, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 113 When tested against Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates T-cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway. reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in B cell lymphoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, B cell lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:272 as residues: Gln-23 to Asn-31, Tyr-42 to Ser-58.
The tissue distribution in B-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of lymphomas, particularly B cell lymphomas. Furthermore, expression of this gene product in B-cells indicates a role in the regulation of the proliferation; survival;
differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.
In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Additionally, the biological activity data supports the notion that the translational product of this gene activates specific immune cells, and therefore may play a role in the initiation of immune system activity.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:123 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1146 of SEQ ID N0:123, b is an integer of 15 to 1160, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:123, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 114 This gene is expressed primarily in neutrophils: IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of certain immune disorders, especially those involving neutrophils. Expression of this gene product in neutrophils indicates a role in the regulation of the proliferation;
survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation. or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses}.
Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Sorne of these sequences are related to SEQ
ID N0:124 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 879 of SEQ ID N0:124, b is an integer of 15 to 893, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:124, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 115 One embodiment of this gene comprises polpeptides of the following amino acid sequence: DIMPASVIFLICEGVLYGVQG (SEQ ID N0:476). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, placental insufficiency; developmental abnormalities; aberrant angiogenesis; abnormal development and/or maintenance of the placenta.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the placenta and. more generally, the vasculature and/or endothelium, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
developing, placental, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression.level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in placental tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of disorders of the placenta. Specific expression within the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. Alternately, this gene product may be produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus. Expression of this gene product in a vascular-rich tissue such as the placenta also indicates that this gene product may be produced more generally in endothelial cells or within the circulation. In such instances, it may play more generalized roles in vascular function, such as in angiogenesis. It may also be produced in the vasculature and have effects on other cells within the circulation, such as hematopoietic cells. It may serve to promote the proliferation, survival, activation, and/or differentiation of hematopoietic cells, as well as other cells throughout the body.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:125 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1035 of SEQ ID N0:125, b is an integer of 15 to 1049, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:125, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 116 This gene is expressed primarily in keratinocytes, as well as in synovial hypoxia and T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, integumentary, immune, or skeletal disorders, particularly wound healing and rheumatoid conditions. Similarly, polypeptides and antibodies directed to these poIypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the integumentary system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
skin, connective tissues, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:275 as residues: Thr-42 to Pro-53, Val-78 to Glu-86, Glu-103 to Met-112, Ala-124 to Gly-131.
The tissue distribution in keratinocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of integumentary disorders, particularly with regard to wound healing. Furthermore, the tissue distribution also indicates that the translation product of this gene is useful for the treatment and/or detection of disorders of the connective tissues (e.g.
arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, s~leroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:126 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1612 of SEQ ID N0:126, b is an integer of 15 to 1626, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:126, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 117 This gene is expressed primarily in hepatoma and testes tumor, and to a lesser extent, in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hepatic, neural, or reproductive disorders, particularly metastatic liver cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer and metabolic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. liver, brain, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, seminal fluid, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in hepatic tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some types of cancer including hepatoma, testes tumor and related metastases.
Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g.
hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:127 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 1163 of SEQ ID N0:127, b is an integer of I S
to I 177, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:127, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 118 This gene is expressed primarily in CD34 positive cells, and to a lesser extent, in pancreatic tumor and spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are IS not limited to, reproductive, endocrine, or immune disorders, particularly pancreatic cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumor, immune and metabolic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, liver, spleen, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, bile, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in pancreatic and CD34 positive cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some types of cancer, especially those involving CD34 cells and pancreatic cancer. Furthermore, expression of this gene product in both CD34 positive cells and spleen indicates a role in the regulation of the proliferation;
survival;
differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, z, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:128 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1262 of SEQ ID N0:128, b is an integer of 15 to 1276, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:128, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 119 This gene is expressed primarily in osteoclastoma, fetal liver/spleen, and to a lesser extent, in primary dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, osteoclastoma; hematopoietic disorders; lymphomas; impaired immunity;
immune disorders; inflammation, in addition to integumentary disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and bone, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, bone, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:2?8 as residues: Thr-23 to Pro-29, Thr-68 to Pro-76.
The tissue distribution in dendritic cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of bone and hematopoietic disorders. Elevated levels of expression of this gene product in osteoclastoma indicates that it may play a role in the survival, proliferation, and/or growth of osteoclasts. Therefore, it may be useful in influencing bone mass in such conditions as osteoporosis. More generally, as evidenced by expression in fetal liver/spleen, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the numbers of stem cells and committed progenitors. Expression of this gene product in primary dendritic cells also indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:129 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1320 of SEQ ID N0:129. b is an integer of 15 to 1334, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:129, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 120 When tested against fibroblast cell lines, supernatants removed from cells containing this gene activated the EGR 1 assay. Thus, it is likely that this gene activates fibroblast cells through a signal transduction pathway. Early growth response (EGR1) is a promoter associated with certain genes that induces various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation.
This gene is expressed primarily in hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, soft tissue cancers, such as hemangiopericytoma, in addition to other proliferative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
circulatory system, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:279 as residues: Pro-49 to Thr-64.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of hemangiopericytoma. Furthermore, the biological activity data demonstrates that the translation product of this gene activates fibroblast cells. Fibroblast cells have the abiliy to undergo vascularization, and thus the translation product of this gene may be involved in disorders of the vascular tissue, such as hemangiopericytoma.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:130 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 518 of SEQ ID N0:130, b is an integer of 15 to 532, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:130, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 121 WO 99/22243 PCT/US98l22376 This gene is expressed primarily in kidney cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, renal or urogenital disorders, particularly nephritis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. kidney, cancerous and wounded tissues) or bodily fluids (e.g.iymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:280 as residues: Pro-33 to Ser-38.
The tissue distribution in kidney cortex indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the kidney, including nephritis. Furthermore, the tissue distribution in kidney indicates that this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:131 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 671 of SEQ ID N0:131, b is an integer of 15 to 685, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:131, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 122 This gene is expressed primarily in spleen from chronic iymphocytic leukemia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disordes, such as chronic lymphocytic leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. spleen, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spleen tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of chronic lymphocytic leukemia. Furthermore, the expression observed predominantly in spleen cells also indicates that the polynucleotides or polypeptides are important in treating and/or detecting hematopoietic disorders, such as graft versus host reaction, graft versus host disease, transplant rejection, myelogenous leukemia, bone marrow fibrosis, and myeloproliferative disease. The polypeptides or polynucleotides are also useful to enhance or protect proliferation, differentiation, and functional activation of hematopoietic progenitor cells (e.g., bone marrow cells), useful in treating cancer patients undergoing chemotherapy or patients undergoing bone marrow transplantation.
The polypeptides or polynucleotides are also useful to increase the proliferation of peripheral blood leukocytes, which can be used in the combat of a range of hematopoietic disorders, including immmunodeficiency diseases, leukemia, and septicemia.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:132 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 715 of SEQ ID N0:132, b is an integer of 15 to 729, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:132, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 123 This gene is expressed primarily in neutrophils, dendritic cells, and CD34 positive cells (Cord Blood).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hematopoietic, or developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, amniotic fluid, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of some types of immune disorders, especially those involving neutrophils. More generally, as evidenced by expression in CD34 positive cells, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the numbers of stem cells and committed progenitors. Expression of this gene product in primary dendritic cells also indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:133 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1065 of SEQ ID NO: I33, b is an integer of 15 S to 1079, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:133, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 124 This gene is expressed primarily in adult lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. respiratory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
respiratory, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in lung tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of respiratory disorders, such as asthma, emphysema, and ARDS. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:134 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between i to 1283 of SEQ ID NO: I34, b is an integer of 15 l80 to 1297, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:134, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 125 The gene encoding the disclosed cDNA is thought to reside on chromosome 19.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.
This gene is expressed primarily in T-cell lymphoma and fetal liver/spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, developmental, or hematopoietic disorders, particularly lymphomas. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:284 as residues: Gln-25 to Phe-43.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of T-cell lymphoma.
Furthermore, expression of this gene product in fetal liver/spleen indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma., immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:135.and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 603 of SEQ ID N0:135, b is an integer of 15 to 617, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:135, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 126 The translation product of this gene shares sequence homology with C9, a gene of unknown function. The gene encoding the disclosed cDNA is thought to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3. One embodiment of this gene comprises the polypeptides of the following amino acid sequence:
GTAFQHAFSTNDCSRNVYIKKNGFTLHRNPIAQSTDGARTKIGFSEGRHAWEV
WWEGPLGTVA VIGIATKRAPMQCQGYVALLGSDDQSWGWNLVDNNLLHNGE
VNGSFPQCNNAPKYQIGERIRVILDMEDKTLAFERGYEFLGVAFRGLPKVCLYP
AVSAVYGNTEVTLVYLGKPLDG (SEQ ID N0:477). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in placenta, and to a lesser extent, in apoptotic T-cells, as well as in smooth muscle, testes, and microvascular endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, reproductive, muscular, vascular, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, amniotic fluid, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells combined with the homology to the C9 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some immune disorders, especially those involving T-cells.
Furthermore, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses), or male infertility.
Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences> such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:136 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1297 of SEQ ID N0:136, b is an integer of 15 to 1311, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:136, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 127 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some immune disorders, especially those involving neutrophils. Furthermore, as evidenced by expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in neutrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:137 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1081 of SEQ ID N0:137, b is an integer of 15 to 1095, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:137, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 128 This gene is expressed primarily in neutrophils; IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues ar cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:287 as residues: Lys-36 to Asp-42.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some immune disorders, especially those involving neutrophils. Furthermore, as evidenced by the expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in neutrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:138 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 678 of SEQ ID N0:138, b is an integer of 1 ~
to 692, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:138, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 129 This gene is expressed primarily in neutrophils, IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, .immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:288 as residues: Pro-32 to Gln-38, Gly-51 to Asp-57.
The tissue distribution in neutrophils indicates that poly nucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of certain immune disorders, especially those involving neutrophils. Furthermore, as evidenced by expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in nuetrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for' the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:139 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 734 of SEQ ID N0:139, b is an integer of 15 to 748, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:139, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 130 This gene is expressed primarily in neutrophils, IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:289 as residues: Gly-22 to Ser-28.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of certain immune disorders involving neutrophils. Furthermore, as evidenced by expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in neutrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:140 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 111$ of SEQ ID N0:140, b is an integer of 15 to 1132, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:140, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 131 This gene is expressed primarily in corpus callosum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, particularly diseases of the brain, such as neurodegenerative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Brian disorders and diseases, including paranoia, schizophrenia, depression, mania, and Alzheimer's disease. Furthermore, elevated expression of this gene product within the corpus callosum of the brain indicates that it may be involved in neuronal survival;
synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. Again. it may also be useful in the treatment of such neurodegenerative disorders as schizophrenia; ALS; or Alzheimer's. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:141 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1098 of SEQ ID N0:141, b is an integer of 15 to 1112, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:141, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 132 The translation product of this gene shares sequence homology with the putative transposase of the Tigger-1 transposon.
This gene is expressed primarily in atrophic endometrium.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, muscular disorders, particularly muscular atrophy. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. reproductive, muscular, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in endometrial tissue combine with the homology to a transposase indicates that polynucleotides and polypeptides corresponding to this gene are useful for DNA repair in atrophying tissue, particularly of the endornetrium.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:142 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1070 of SEQ ID N0:142, b is an integer of 15 to 1084, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:142, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 133 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARAFQHLMVADHSHFHRTLIKQPSMIPNATFYHIF (SEQ ID
N0:478). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, soft tissue tumors, particularly hemangiopericytoma, or other proliferative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:292 as residues: Ser-39 to Ser-44.
The tissue distribution in hemangiopericytoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of various soft-tissue tumors, in addition to other proliferative disorders which may afflict other tissues or cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
t90 ID N0:143 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1036 of SEQ ID N0:143, b is an integer of 15 to 1050, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:143, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: I34 This gene is expressed primarily in hypothalamus of a schizophrenic patient.
and to a lesser extent in spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural or immune disorders,particularly Schizophrenia or neurodegenerative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the central nervous and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, immune, hematopoietic, spleen, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in hypothalamus indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Schizophrenia, as well as other central nervous system and immune system disorders.
Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania.
dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, disorders of the endocrine system, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:144 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1099 of SEQ ID N0:144, b is an integer of 15 to 1113, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:144, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 135 The translation product of this gene shares sequence homology with a chicken ring-finger-zinc finger protein, C-RZF, in addition to, the human multiple membrane spanning receptor TRC8 which is thought to serve as a signaling receptor in renal and thyroid carcinomas. (See Genbank Accession No.gi13395787 (AF064801 )) The TRC8 locus has been described in a family with classical features of hereditary renal cell carcinoma. The 8q24. l (locus of TRCB) breakpoint region encodes the 664-as multiple membrane spanning protein, TRCB, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular Ioop that participates in the binding of sonic hedgehog. In the 3;8 translocation, TRC8 infused to FHIT (fragile histidine triad gene) and is disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. In a series of sporadic renal carcinomas, an acquired TRCB mutation was identified. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
ARALPEIKGSRLQEINDVCAICYHEFTTSARITPCNHYFHALCLRKWLYIQDTCP
MCHQKVYIEDDIKDN
SNVSNNNGFIPPNETPEEAVREAAAESDRELNEDDSTDCDDDVQRERNGVIQHT
GAAAGRI (SEQ ID N0:479), FSTQAQQLEEFNDDTD (SEQ ID N0:480), RLQE
INDVCAICYHEFTTSARI (SEQ ID N0:48 I ), LYIQDTCPMCHQKVYIEDDI (SEQ
ID N0:482), VSNNNGFIPPNETPEEAVREA (SEQ ID N0:483), and/or DDSTDCD
DDVQRERNGVIQHTGAAAG (SEQ ID N0:484). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 8. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 8.
This gene is expressed primarily in human embryonic tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. developmental abnormalities, particularly congenital defects or proliferative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, renal, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in embryonic tissue, combined with the homology to ring finger-zinc finger protein and the human TRC8 receptor indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of abnormalities of the embryonic tissues. in particular proliferative disorders.
In addition, polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, detection, and/or treatment of developmental disorders. The relatively specific expression of this gene product during embryogenesis indicates that it may be a key player in the proliferation, maintenance, and/or differentiation of various cell types during development. It may also act as a morphogen to control cell and tissue type specification. Because of potential roles in proliferation and differentiation, this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. Moreover,this protein may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:145 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 671 of SEQ ID N0:145, b is an integer of 15 to 685, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:145, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 136 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VAGITGAHHHAQLIFVLLVEMGFHHV GQAGLKLLTSDN
PRTSASQSAGITGMSXGRRITCGQEFKTAVSYNCTTALQPDRAKLCFLFKKKK
KISIQ RTLPGIKRVIYNYERVDSSKGHNSQVQWAHA CNPSTLGGRGGQIV
(SEQ ID N0:485), AGITGAHHHAQLIFVLLVEMGF (SEQ ID N0:486), RVIYN
YERVDSSKGHNSQVQWAHACNP (SEQ ID N0:487). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in microvascular endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular or endothelial disorders, such as the following:
arteriosclerosis, tumorigenesis, stroke, embolism, aneurysm, microvascular disease, and various cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.vascular, endothelial, S cardiovascular, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in microvascular endothelial tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of vascular disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are~related to SEQ
ID N0:146 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1024 of SEQ ID N0:146, b is an integer of 15 to 1038, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:146, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 137 The gene encoding the disclosed cDNA is believed to reside on chromosome 2.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2.
This gene is expressed primarily in fetal tissues, most notably fetal cochlea and fetal lung, and to a lesser extent, in rhabdomyosarcoma and healing groin wound tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include.
but are not limited to, embryological/developmental abnormalities; hearing defects;
respiratory diseases; rhabdomyosarcoma; general cancers and other proliferative conditions;
fibrosis; wound healing. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryo/fetus or of striated muscle cells, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, pulmonary, auditory, muscle, fibroid, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases involving abnormal cellular proliferation, such as cancer. Expression of this gene product in rapidly proliferating cells, such as those found in the embryo; in rhabdomyosarcomas;
and in wound healing tissue, indicates that this gene may play a role in controlling or promoting cell proliferation. Alternately, expression of this gene in fetal tissues indicates that it may play a role in cellular development and differentiation, particularly of the auditory system as well as the lungs. Thus, this gene product may be useful in the treatment andlor diagnosis of hearing defects, as well as respiratory disorders.
Expression of this gene product in rhabdomyosarcoma indicates that it may play a role in the progression of such cancers, and may also be involved in metastasis and/or angiogenesis. Additionally, expression in wound healing tissues again indicates a role in the proliferation of connective tissue types involved in wound healing, as well as in the fibrosis and scarring that accompanies the wound healing process. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:147 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 837 of SEQ ID N0:147, b is an integer of 15 to 851, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:147, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 138 The gene encoding the disclosed cDNA is believed to reside on chromosome 1.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1.
This gene is expressed primarily in adult brain, and to a lesser extent, in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders and diseases of the brain, particularly neurodegenerative and behavior conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:297 as residues: Pro-25 to Ser-30, Thr-36 to Ser-47.
The tissue distribution in neural tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders and diseases of the brain, particularly paranoia, Alzheimer's, depression, schizophrenia, and mania. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neopIasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many poIynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences, are related to SEQ
ID N0:148 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 600 of SEQ ID N0:148, b is an integer of 15 to 614, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:148, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 139 This gene is expressed primarily in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. neural disorders, particularly neurodegenerative disorders, such as Alzheimers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(sl. For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in cerebellum indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of brain diseases and disorders. Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as ES'T sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:149 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1186 of SEQ ID N0:149, b is an integer of 15 to 1200, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:149, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: I40 This gene is expressed primarily in brain tissue of a patient with Alzheimer s disease, and to a lesser extent, in human adipose tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. neural or adipose-related disorders, particularly neurodegenerative disorders, such as Alzheimer's disease. Sinularly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, metabolic, adipose, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neural and adipose tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Alzheimer's disease and other nervous system disorders.
Moreover, poIynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. More specifically, the protein product of this gene may show utility in the treatment, diagnosis, and/or prevention of neural disorders which occur secondary to aberrations in fatty-acid metabolism, such as improper development of the myelin sheath of nerve cells, for example. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:150 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 669 of SEQ ID NO:150, b is an integer of 15 to 683, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:150, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 141 This Gene is expressed primarily in T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited ta, immune or hematopoietic disorders, particularly T cell leukemia, immunodeficiencies, and inflammatory conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:300 as residues: Asn-62 to Leu-68.
The tissue distribution T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of T cell leukemia and other disorders of the immune system. Moreover, this gene product may play a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene DE3IIlANDES OU BREVETS VOLUMINEUX
LA PRESENTS PARTIE DE CETTE DEMANDS OU CE BREVET
CECi EST LE TOME ~ DE
NOTE. Pour les tomes additionels, veuillez contacter to Bureau canadien des brevets JUMBO APPLlCATIONS/PATENTS .
THIS SECTION OF THE APPUCATIONIPATENT CONTAINS MORE
'THAN ONE VOLUME
THIS IS VOLUME ~_ OF
' NOTE: For additional volumes-phase contact the Canadian Patent Office .
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues}
or cell type(s). For a number of disorders of the above tissues or cells. particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, testicular, and cancerous and wounded tissues) or bodily fluids (e.g. lymph. seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in testis, the homology to an erythrocyte membrane antion-transport protein, in addition to, the detected calcium flux biological activity 5 indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of autoimmune diseases and other immune diseases such as cancer, particularly in, but not limited to, testicular tissue. Similarly, the translation product of this gene may be important in maintaining normal, cellular homeostasis.
Therefore, the protein, as well as antibodies directed to the invention, is beneficial as a therapeutic in 10 order to ameliorate conditions related to aberrant cellular pH regulation (for example, use antibodies to decrease the presence of the protein, or possibly in gene therapy applications in order to replace a defective form, or alternatively, increase the expression of either the endogenous or modified form of the invention).
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker 15 and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:30 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the 20 scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 850 of SEQ ID N0:30, b is an integer of 15 to 864, where both a and b correspond to the positions of nucleotide residues shown in 25 SEQ ID N0:30, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 21 30 This gene is expressed primarily in the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, which include, but are not limited to, disorders of the 35 brain and central nervous system, such as neurodegenerative conditions and/or depression. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:180 as residues: His-13 to Leu-18.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders of the brain and central nervous system. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease., Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:31 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 905 of SEQ ID N0:31, b is an integer of 15 to WO 99/22243 PC'f/US98/22376 919, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:31, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 22 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
PCLQVIGIDFCRLLLMCLVLKRNLTVPFSSYSPLKTITCITSEQIAWSNFFRQKL
GVRAK FFQGACLHTSKVVICLNLPIISIQRADIRMWWLVVNTPYARGVNN
(SEQ ID N0:340). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in the spinal cord.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, any of a variety of nervous system and neuromuscular disorders including, but not limited to, amyotropic lateral sclerosis, musculuar dystrophy, and inherited and non-inherited forms of chorea. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system and neuromuscular systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spinal cord indicates that this gene could be used for the treatment of spinal cord injuries. The protein product of this gene could be injected into the spinal cord to promote or control growth following injuring or degeneration.
Alternatively cells expressing this gene could be injected or transferred into the spinal cord by other means as a treatment promoting the growth or regulation of growth following spinal cord injury or degeneration. This gene may also be useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases.
peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:32 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 942 of SEQ ID N0:32, b is an integer of 15 to 956, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:32, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 23 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VVSVCVLETGQLGPAALCRSV (SEQ ID N0:341).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, which include, nut are not limited to, inflammatory diseases or neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid} or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treament of the inflammatory conditions. Moreover, This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:33 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 552 of SEQ ID N0:33, b is an integer of 15 to Sb6, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:33, and where b is greater than or equal to a + 14.
WO 99!22243 PGT/US98/22376 FEATURES OF PROTEIN ENCODED BY GENE NO: 24 S In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
NISVHGFPVPCLRQRLQGPCHPKCCPHXISSGKPRSSFSPSSYHCKFSRNATLL
VVPNIFSYMQSSFLIPQTSKYYILXPYAXTXRPIKXIFKQAKQ (SEQ ID N0:342), IYNDMMMEKKKTEVYQKRXSGDNTWGGKGLVAFVSSMEQGIHVQRCFIANL
10 KFSSPGV (SEQ ID NO: 343), YDDGEKEDRGLPEEMXWGQHLGWQGPCSL
CLKHGTGNPCTEMFYCQFKIFIS WCLIPLVFARLGDFRDRPGWIFSWRYHLKH
TVWGGYNIIML (SEQ ID NO: 344), TPGDENFKLAIKHLCTWIPCS (SEQ ID NO:
345), IRHEIFLTIESFCPSAPRGEDDDNLLRTSRVPDI (SEQ ID N0:346), IRGSIP
GHKKMHLS FNVAAQWSLLKPLVLREEGALFLTHDQLESKNSWTLSIGPRV
KGKQSHSTVQLANILHVFXAPDXYHFVNTSLQLFLEYTVMCMLCENK QKT
LGR (SEQ ID N0:347), EPEVTQVXSXELTFQ PRKAGAKVTAGKSHHQVIHWE
FEIMLSSYSTDVPLWFLKFFSSNLPQTYFPHSGVKKWGSCFSLPWRDSPPLT
FISLLSSHLTTFHLYHLHHGIICLGFSVYFHRAYTSLCILETAVGSY (SEQ ID
20 N0:348), WSLLKPLVLREEGALFLTHDQLESK (SEQ ID N0:349), WFAKKK
GKQSHSTVQLANILHV (SEQ ID N0:350), AGKSHHQVIHWEFEIMLSSYSTDVP
(SEQ ID N0:351), and/or HGIICLGFSVYFHRAYTSLCILETAV (SEQ ID N0:352).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in smooth muscle.
25 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, muscular or vascular disorders, which include, but are not limited to defective organ innervation; deficiencies in neuronal survival; peristaltic abnormalities;
30 digestive disorders; perturbations of the vasculature. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the smooth muscle, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types 35 (e.g., cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in smooth muscle tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or S treatment of disorders that result from failures of normal smooth muscle function. For example, this.gene product may represent a soluble factor produced by smooth muscle that regulates the innervation of organs or regulates the survival of neighboring neurons. Likewise, it may be involved in controlling the digestive process, and such actions as peristalsis. Similarly, it may be involved in controlling the vasculature in areas where smooth muscle surrounds the endothelium of blood vessels. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:34 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1550 of SEQ ID NO:34, b is an integer of 15 to 1564, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:34, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 25 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KRLTINARVHLWTLKSVPL (SEQ ID N0:353), EYVFNMX
XYSKSRAISPLSGPYTPRGTTPLPIIPEPGARQRDHPAS LKYAKIIQTKLFAL
PYPKETSMKAVA (SEQ ID N0:354), andlor ETVPPRSSQFLKITXGPARSMSLIX
XAIQNPEPYLLYLALIPQEALLLYLSSQSQVPGNETTPPV (SEQ ID N0:355).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not linvted to, immune system disorders. which include, but are not limited to lupus, inflammatory conditions, and immunodeficiencies such as AIDS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:184 as residues: Ser-21 to Thr-34, Thr-38 to Glu-43.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Expression of this gene product in T-cells indicates a role in regulating the proliferation; survival; differentiation;
and/or activation of hematopoietic cell lineages, including blood stem cells. This Gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:35 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1021 of SEQ ID N0:3S, b is an integer of 1S
S to 1035, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:3S, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 26 The translation product of this gene was determined to have homology to the human IB3089A protein which is thought to play an important role in tumor suppression {See Genbank Accession No.gi13041877 (AF027734)).In specific embodiments, polypeptides of the invention comprise the following amino acid 1 S sequence: NEVSFSLSLGFSPREFARWKVNNLAL ERKDFFSLPLPLAPEFIRNI
RLLGRRPNLQQVTENLIKKYGTHFLLSATLGGKQHHNPKLIGCQTIGNNV
KTRVA (SEQ ID N0:3S6), VPYFLIRFSVTCCRLGLLPRRRMFRIN SGARGNG
KLKKSFLSRAK LFTFQRANSLGEKPRDKEKLTSFQSKRHKI (SEQ ID N0:3S7), and/or EMSAVLFNQIFCNLLQIGSPSKEANVPDKLWGKRQWQTEEVLPFQSQV
VHLPTGKLPGGKAKG (SEQ ID N0:3S8). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human fibrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 2S biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders afflicting endothelial, muscular. and extracellular matrix tissues, which include, but are not limited to fibrosarcomas and bladder cancer.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the integumentary system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endothelial, urogenital,renal, muscular, and cancerous and wounded tissues) or bodily fluids {e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken 3S from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:185 as residues: Pro-49 to Asp-68.
The tissue distribution in human fibrosarcoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of various cancers, particularly fibrosarcomas and fibroids. Moreover, the expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many poiynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:36 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 606 of SEQ ID N0:36, b is an integer of IS to 620, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:36, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 27 This gene is expressed primarily in human tonsil.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, which include, but are not limited to inflammation and infectious diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids {e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an 5 individual not having the disorder.
The tissue distribution in tonsils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis of inflammation and infectious diseases. Moreover, this gene product may play a role in regulating the proliferation;
survival; differentiation; and/or activation of hematopoietic cell lineages, including 10 blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological 15 disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as 20 autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, 25 antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:37 and may have been publicly available prior to conception of the present 30 invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 959 of SEQ ID N0:37, b is an integer of I S to 35 973, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:37, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 28 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
HYHGSGFLIKEFGSFLSLLCMLSCPYVFCHGMLEQEVPSSVVSPSTLDF PTSR
TVNKFLFKLPSLWYSVIATQNGLKQKIRETFLFVQFSQMPRWHKLE (SEQ ID
N0:359}. Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adipose and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. metabolic or neural conditions, which include but are not limited to obesity and disorders of the brain and central nervous system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, metabolic tissues, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neural and adipose tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of obesity and disorders of brain and central system. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. In addition, considering the expression within both adipose tissue and brain indicates that the protein may be benefical either as a target for gene therapy, or as a novel therapeutic to ameliorate conditions affecting myelin sheath development in neurons, or other disorders involving neural tissue which occur secondary to aberrant fatty-acid metabolism. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:38 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 824 of SEQ ID N0:38, b is an integer of 15 to 838, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:38, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 29 The gene encoding the disclosed cDNA is thought to reside on chromosome I 1.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11. One embodiment of this gene comprises polypeptides of the following amino acid sequence:
FCKHNGSKNVFSTFRTPAVLFTGIVALYIASGLTGFIGLEVVAQLFNC (SEQ ID
N0:360). An additional embodiment is the polynucleotides encoding the polypeptides.
This gene is expressed primarily in suppressor T cells, endothelial cells, dendritic cells, and infant brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include.
but are not limited to, immune system disorders related to abnormal activation of T
cells.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the S immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. hematopoietic, developmental;
neural, immune, endothelial, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e.; the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:188 as residues: Tyr-14 to Leu-24, Pro-S9 to Gln-66.
The tissue distribution in immune cells indicates that polynucleotides and 1S polypeptides corresponding to this gene are useful for treating disorders of the immune system related to altered activation of T cells. Furthermore. this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of immune disorders.
Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility 2S in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:39 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more 3S polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to S93 of SEQ ID N0:39, b is an integer of 1 S to a9 607, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:39, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 30 This gene is expressed primarily in the fetus and in tumor cell types.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of rapidly growing tissues such as cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of rapdiIy growing tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. fetal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene primarily in the developing fetus indicates a role in the treatment and/or detection of developmental disorders and growth defects. In addition, expression in tumor cell types indicates a role in the detection and/or treatment of tumors. Furthermore, expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:40 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 868 of SEQ ID N0:40, b is an integer of 15 to 882, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:40, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 31 This gene is expressed primarily in salivary gland, and to a lesser extent, in 10 other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to> digestive and immune disorders. Similarly, polypeptides and antibodies 15 directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the salivary gland and other glands of the exocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. exocrine, digestive. cancerous and 20 wounded tissues) or bodily fluids (e.g. lymph, serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
25 N0:190 as residues: Glu-25 to Gly-31, Tyr-62 to Thr-68.
The tissue distribution in salivary gland tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of digestive and immune system disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the 30 above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:41 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the 35 scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 945 of SEQ ID N0:41, b is an integer of 15 to 959, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:41, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 32 The gene encoding the disclosed cDNA is thought to reside on chromosome 12.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12.
This gene is expressed primarily in brain tissue of adults, as well as infants.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. neurodegenerative and behavioural disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central and peripheral nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:191 as residues: Ser-16 to Val-33.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. Furthermore, expression of this gene product within the brain indicates that it may be involved in neuronal survival;
synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:42 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 861 of SEQ ID N0:42, b is an integer of 15 to 875, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:42, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 33 This gene is expressed primarily in the synovium.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases affecting the synovial lining including arthritis and autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the musculo-skeletal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. endothelial, skeletal, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for use as a factor that may protect against articular damage or promote growth of the cells in articulating joints.
Furthermore, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g.
arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:43 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 616 of SEQ ID N0:43, b is an integer of 15 to 630, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:43, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 34 When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus. it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the 3ak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in B-cell lymphoma cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune disorders, such as diseases of B-cell lineage including lymphomas lymphoblastic leukemias, myelomas and hairy cell leukemia.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:193 as residues: Lys-82 to Pro-90.
The tissue distribution and biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for for the treatment and or diagnosis of diseases of B-cell lineage including cancer. This factor may be useful in the terminal differentiation of malignant cells or may act as a growth factor for B-cell proliferation or differentiation, which is supported by the biological assay data. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:44 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 557 of SEQ ID N0:44, b is an integer of 15 to 571, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:44, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 35 When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore. activation of the Jak-STAT pathway. reflected by the binding of the GAS
5_5 element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in osteoclastoma derived stromal cells, placenta, pancreas and several tumor derived cells and to a lesser extent in brain, melanocytes, dendritic cells, and several other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(sj or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, tumors of the pancreas, uterus, ovary, bone, or adrenal gland.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. placenta, pancreas. cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating or diagnosing tumors of the reproductive organs, pancreas, or bone marrow. Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, andlor prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g.
diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:45 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 916 of SEQ ID N0:45. b is an integer of 15 to 930, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:45, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 36 When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay. Thus, it is likely that this gene activates leukemia cells through the Jak-STAT signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the ISRE
element, can be used to indicate proteins involved in the proliferation and differentiation 1 S of cells.
This gene is expressed primarily in kidney and to a lesser extent in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. renal and nervous system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders ' of the above tissues or cells, particularly of the renal and nervous systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.renal, urogenital, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:195 as residues: Lys-117 to Lys-126.
The tissue distribution of this gene in kidney tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of renal disorders including kidney failure and Wilms Tumor in addition to the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:46 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 423 of SEQ ID N0:46, b is an integer of 15 to 437, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:46, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 37 One embodiment of this gene comprises polypeptides of the following amino acid sequence:
MPKPGAATQRTLLCLPRLHPASGPPLPXAGPLRGLRQLPALPVPAASCRRRPAP
RLCAAGPCTVGPAASPHAPPHGCPPPASLAHV AHRQSVSGTVCLGLRDGHV
RGGCAAVRGXAALPWDAAAAGPDHMGVGSGPALL (SEQ ID N0:361). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in pituitary and to a lesser extent in thymus and breast.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, metabolic and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). 1~or a number of disorders of the above tissues or cells, particularly of the endocrine and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types or cell types (e.g. thymus, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of endocrine, metabolic, and immune disorders including growth and developmental defects, in addition to the treatment or detection of immune or hematopoietic disorders including arthritis, asthma, immunodeficiency diseases and leukemia. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:47 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1010 of SEQ ID N0:47, b is an integer of 1S
to 1024, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:47, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 38 This gene is expressed primarily in hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular disorders such as stroke, aneuyrism, cardiac arrest, hemorrhage. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. circulatory system, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:197 as residues: Cys-14 to Gly-23, Met-4S to Gly-51.
The tissue distribution of this gene solely in hemangiopericytoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and or detection of vascular disorders including hemorrhaging, aneuyrism, stroke and cardiac arrest. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:48 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 449 of SEQ ID N0:48, b is an integer of 15 to 463, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:48, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 39 The translation product of this gene shares sequence homology with a serine protease which is thought to be important in regulating the availibility and action of proteins in vivo.
This gene is expressed primarily in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. disorders of the central nervous system related to abnormal growth factor regulation, including neurodegenerative conditions such as Alzheimers disease and psychiatric illness such as Schizophrenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Central Nervous System, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. CNS, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:198 as residues: Ser-17 to Gln-22.
5 The tissue distribution in neural tissue, combined with the homology to serine proteases indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders of the central nervous system including neurodegenerative diseases and psychiatric disorders. Furthermore, expression of this gene product within cerebral tissue indicates that it may be involved in neuronal survival;
synapse formation;
10 conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. It may also be useful in the treatment of such neurodegenerative disorders as schizophrenia; ALS; or Alzheimer's.Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
15 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:49 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
20 Accordingly, preferably excluded from the present invention are one or more polynucIeotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 871 of SEQ ID N0:49, b is an integer of 15 to 885, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:49, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 40 This gene is expressed primarily in CD34 depleted buffy coat.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
WO 99/22243 PCT/US9$/22376 immune, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in CD34 depleted huffy coat tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders of the immune system including autoimmune diseases. Furthermore, expression of this gene product in CD34 depleted huffy coat indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as; antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy-targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences we related to SEQ
ID NO:50 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 833 of SEQ ID NO:50, b is an integer of 15 to 847, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:50, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 41 This gene is expressed primarily in B-cell lymphoma cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of B-cell lineage including lymphomas lymphoblastic leukemias, myelomas and hairy cell leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues j or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immunce cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for for the treatment and or diagnosis of diseases of B-cell lineage including cancer. This factor may be useful in the terminal differentiation of malignant cells or may act as a growth factor for B-cell proliferation or differentiation. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:S 1 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 566 of SEQ ID NO:S 1, b is an integer of 15 to 580, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:51, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 42 This gene is expressed primarily in brain and CD34 depleted huffy coat.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, autoimmune disorders particularly those of the central nervous system such as multiple sclerosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, neural, and cancerous and wounded tissues) or bodily fluids (e.g. lymph. amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:201 as residues: Pro-35 to Ala-40.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating autoimmune disorders such as multiple sclerosis. Furthermore, expression of this gene product in CD34 depleted huffy coat indicates a role in the regulation of the proliferation; survival;
differentiation;
andlor activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:52 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 584 of SEQ ID N0:52, b is an integer of 15 to 598, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:52, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 43 This gene is expressed primarily in tissues of the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological and neurodegenerative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. CNS, brain, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful as a neuronal protective agent and as a growth factor for cells of the central or peripheral nervous system.
Furthermore, expression of this gene product within the brain indicates that it may be involved in neuronal survival; synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:53 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 557 of SEQ ID N0:53, b is an integer of 15 to 571, where both a and b correspond to the positions of nucleotide residues shown in 10 SEQ ID N0:53, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 44 15 The gene encoding the disclosed cDNA is thought to reside on chromosome 9.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 9.
This gene is expressed primarily in embryo and fetal tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as 20 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above 25 tissues or cells, particularly of the embryo and fetal tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
fetal tissues, develpomental, cancerous and wounded tissues) or bodily fluids (e.g.
lymph, amniotic fluid, serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the 30 standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in embryonic and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of developmental disorders. Furthermore, the tissue distribution indicates 35 that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other proliferative disorders.
Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division.
Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the abovelisted tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:54 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1233 of SEQ ID N0:54, b is an integer of 15 to 1247, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:54, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 45 The gene encoding the disclosed cDNA is thought to reside on chromosome 2.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2.
This gene is expressed primarily in infant brain, placenta, sane immune tissues.
and, to a lesser extent, in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and immune disorders. Similarly. polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the early developmental stage tissues and immune tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:204 as residues: Val-32 to Met-39, Leu-44 to Val-49.
The tissue distribution in fetal and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of developmental and immune disorders. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other proliferative disorders.
Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division.
Additionally, the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and/or survival of hematopoietic cell lineages. In such an event, this gene may be useful in the treatment of lymphoproliferative disorders, and in the maintenance and differentiation of various hematopoietic lineages from early hematopoietic stem and committed progenitor cells. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. The protein product of this gene is useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome. meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder; learning disabilities, ALS, psychoses . autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover; the gene or gene product may also play a role in the treatment andlor detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies 'directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:55 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 834 of SEQ ID NO:55, b is an integer of 15 to 848, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:S~, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 46 When tested against Jurkat T-cells, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates T-cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in brain tissues, and to a lesser extent, in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neuronal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, brain, cancerous and wounded tissues) or bodily fluids {e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:205 as residues: Ser-33 to Ser-44.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal and immune system disorders. Furthermore, expression of this gene product in T-cells, as well as the observed biological activity of this gene product, indicates that this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Alternatively, the expression within brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries. ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities. ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NU:56 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 655 of SEQ ID N0:56, b is an integer of 15 to 669, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:56, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 47 When tested against U937 Myeloid cell lines, supernatants removed from cells 10 containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. When tested against K562 leukemia cell lines, supernatants removed from cells containing this gene activated the ISRE assay.
Thus, it 15 is likely that this gene activates leukemia cells through the Jak-STAT
signal transduction pathway. The interferon-sensitive response element is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT
pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the 20 binding of the GAS element, can be used to indicate proteina involved in the proliferation and differentiation of cells. Contact of cells with supernatant expressing the product of this gene increases the permeability of bovine chondrocytes to calcium.
Thus, it is likely that the product of this gene is involved in a signal transduction pathway that is initiated when the product of this gene binds a receptor on the surface of 25 the chondrocyte cells. Thus, polynucleotides and polypeptides have uses which include, but are not limited to, activating bone cells.
This gene is expressed primarily in breast and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 30 biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pregnancy disorders including miscarriage. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast and placenta , expression of this 35 gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. placental tissues, breast, bone, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in both placenta and breast indicates a role for this protein in the treatment and/or detection of miscarriages in suspect individuals, of birth defects, of breast cancer, and female infertility. Furthermore, the biological assay data strongly indicates that the translation product of this gene is actively involved in the initiation of several signal transduction pathways and the activation of several cell types.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:57 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 666 of SEQ ID N0:57, b is an integer of 15 to 680, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:57, and where b is greater than or equal to a + 14 FEATURES OF PROTEIN ENCODED BY GENE NO: 48 The gene encoding the disclosed cDNA is thought to reside on chromosome 11.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11. One embodiment of this gene comprises the polypeptides of the following amino acid sequence:
MWGQPRPVDSVWSSSIPKKSVESNDNKSHLHKREH (SEQ ID N0:362), MTTKAIFTKGNIDSLSFKSNMWSVYI (SEQ ID N0:363). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in the pancreas.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pancreatic related disorders such as diabetes. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. pancreas, endocrine, metabolic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, bile, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in pancreatic tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment/detection of endocrine disorders and metabolic disorders associated with the pancreas including diabetes, panereatitis, and pancreatic cancer. Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:58 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 510 of SEQ ID N0:58. b is an integer of 1 S to 524, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:58, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 49 This gene is expressed primarily in chondrosarcoma tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, including diseases of the skeletal system, particularly with respect to the cartilagenous structures and also cancer of these tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. bone, connective, and cancerous and wounded tissues) or bodily fluids (e.g.
lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in chondrosarcoma tumors indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment/diagnosis of cartilage disorders including arthritis and cancer. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:59 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To Iist every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 4I3 of SEQ ID N0:59, b is an integer of 15 to 427, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:59, and where b is greater than or equal to a + 14 FEATURES OF PROTEIN ENCODED BY GENE NO: 50 The translation product of this gene shares sequence homology with sorbinwhich is thought to be important in the manufacture of vitamin C.
Additionally, sorbin is thought to be important in the process of stimulating water and electrolyte absorption in various cells in the body. Porcine Sorbin has activity in stimulating water and electrolyte absorption across mucosa. It has been pursued as a regulator of electrolyte absorption in the nasal and enteric mucosa. This gene was identified in hypothalamus suggesting that it could play a role in the CNS regulation of water or electrolyte absorption.
This gene is expressed primarily in human hypothalamus tissue from a patient suffering from Alzheimer's disease.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurologic disorders (eg. Alzheimer's disease). Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunoIogical probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:209 as residues: Leu-29 to Leu-37, Gln-65 to Asp-70, Gln-85 to Gly-95.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Alzheimer's disease. Additionally, the translation product of this gene, based upon its homology to the porcine sorbin, could be useful for the detection and/or amelioration of disorders involving the CNS regulation of water or electrolyte absorption.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:60 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1249 of SEQ ID N0:60, b is an integer of 15 to 1263, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:60, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 51 This gene is expressed primarily in synovium. and to a lesser extent, in other tissues.
5 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. synovial diseases such as synovial sarcoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes 10 for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the synovium. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
connective tissues. cancerous and wounded tissues) or bodily fluids le.g.
lymph.
serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level. i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in synovium indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of '.0 synovial diseases such as arthritis. Furthermore, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. trauma, tendonitis. chrondomalacia and inflammation). such as in the diagnosis or treatment of various autoimmune disorders 5 such as rheumatoid arthritis. lupus. scleroderma. and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita. familial osteoarthritis.
Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or ~ immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:61 and may have been publicly available prior to conception of the present invention. Preferably. such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 706 of SEQ ID N0:61, b is an integer of 15 to 720, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:61, and where b is greater than or equal to a + I4.
FEATURES OF PROTEIN ENCODED BY GENE NO: 52 This gene is expressed primarily in immune tissues and fast-growing tissues, such as tumor and early-stage developmental tissues, and, to a lesser extent, in some other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and growth related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune tissues and fast-growing tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. developmental, immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:211 as residues: Ala-28 to Ala-47.
The tissue distribution in immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of immune and growth related diorders. Furthermore, expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:62 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the S scope of the present invention. To list every related sequence is cumbersome.
Accordingly,,preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to S7S of SEQ ID N0:62, b is an integer of 1S to 589, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:62, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: S3 1 S One embodiment of this gene comprises polypeptides of the following amino acid sequence: DSXLDRRPSGPDVKFLSNKHHFSMVC (SEQ ID N0:364). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in spleen, and to a lesser extent, in a range of hematopoetic cell types.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoeitic disorders. Similarly, polypeptides and antibodies directed to these poiypeptides are useful in providing immunological probes 2S for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoetic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. spleen, immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:212 as residues: Cys-2S to Trp-30.
3S The tissue distribution of this gene in spleen tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma.
immunodeficiency diseases and leukemia. Expression of this gene product in spleen indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other S processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation andJor proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a 1 S tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences we related to SEQ
ID N0:63 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 672 of SEQ ID N0:63, b is an integer of 1 S to 686, where both a and b correspond to the positions of nucleotide residues shown in 2S SEQ ID N0:63, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 54 This Qene is expressed primarily in human normal breast, and to a lesser extent.
in dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are 3S not limited to, glandular problems involving cells of epithelial origin including breast cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the female endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. breast, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
NO:213 as residues: Ser-32 to Asn-44.
The tissue distribution in breast tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or treatment of both malignant and non-malignant problems of the breast tissues, including cancer.
Alternatively. the expression in dendritic tissue indicates polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
iD N0:64 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 438 of SEQ ID N0:64, b is an integer of 15 to 452, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:64, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 55 When tested against U937 Myeloid cell lines, supernatants removed from cells 5 containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
10 Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in early stage human tissues, immune tissues, and to a lesser extent, in other tissues such as prostate.
1 S Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, development and immune related diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes 20 for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and early stage human tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine. synovial fluid and 25 spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in embryonic and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis 30 and treatment of developmental and immune related diseases. The biological activity data supports the assertion that the translation product of this gene is useful in the treatment andlor diagnosis of diseases related to the immune system. Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker andlor immunotherapy target for the above listed tissues.
35 Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:65 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 356 of SEQ ID N0:65, b is an integer of 15 to 370, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:65, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 56 The translation product of this gene shares sequence homology with medicago saliva salt-inducible protein.
This gene is expressed primarily in human chronic synovitis.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skeletal or rheumatoid disorders, particularly, chronic synovitis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. connective tissues, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:215 as residues: Lys-30 to Ser-44, Pro-77 to His-82.
The tissue distribution in synovium indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of and as a therapeutic agent for chronic synovitis. In addition, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scieroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:66 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 973 of SEQ ID N0:66, b is an integer of 15 to 987, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:66, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 57 The translation product of this gene shares high sequence homology with the rat and mouse peroxisomal membrane proteins [gi1297437], which appears to play a crucial role in transporting proteins into the organelle. Some human genetic disorders involving peroxisome biogenesis, such as Zellweger syndrome, may be caused by genetic defects of the import machinery located in the peroxisomal membrane. When tested against fibroblast cell lines, supernatants removed from cells containing this gene activated the EGRl assay. Thus, it is likely that this gene activates fibroblast cells through a signal transduction pathway. Early growth response 1 (EGR 1 ) is a promoter associated with certain genes that induces various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation.
This gene is expressed primarily in normal human liver.
Therefore, polynucIeotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the hepatic system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic disorders and liver metabolic diseases, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. liver, cancerous and wounded tissues) or bodily fluids (e.g. lymph, bile, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression Level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:216 as residues: Lys-57 to Ser-66.
The tissue distribution in liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases relating to the liver. Furthermore, the homology indicates that the translational product of this gene may be useful in the detection and treatment of a number of disorders resulting from the improper transport of proteins into the organelle due to defects in peroxisomal membrane proteins, such as Zellweger syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:67 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1004 of SEQ ID N0:67, b is an integer of 15 to 1018, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:67, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 58 The gene encoding the disclosed cDNA is thought to reside on chromosome 4 Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4.
This gene is expressed primarily in human fetal dura mater.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include.
but are WO 99/22243 PCTlUS98/22376 not limited to, developmental or neurologic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:217 as residues: Ala-19 to Lys-34.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neurological diseases. Furthermore, the tissue distribution indicates that polynucleotides .
and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, and/or sexually-linked disorders.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:68 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 748 of SEQ ID N0:68, b is an integer of IS to 762, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:68, and where b is greater than or equal to a + 14.
WO 99/22243 PCTIUS98/2237b FEATURES OF PROTEIN ENCODED BY GENE NO: 59 The gene encoding the disclosed cDNA is thought to reside on chromosome 16.
5 Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 16.
This gene is expressed primarily in T helper cell and human uterine cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 10 biological sample and for diagnosis of diseases and conditions which include, but are not limited to, relating to hemopoietic and uterus disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and female reproductive 15 system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level. i.e., the expression level 20 in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-helper cells and uterine tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders relating to both the immune and female reproductive systems. Expression of this gene product in T-cells indicates a role in the 25 regulation of the proliferation; survival; differentiation; andlor activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, 30 the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product 35 may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:69 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 616 of SEQ ID N0:69, b is an integer of 15 to 630, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:69, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 60 This gene is expressed primarily in human fetal epithelium, and to a lesser extent, m testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental or reproductive disorders, in addition to diseases of the integumentary system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the diseases relating to the epithelium; expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
epithelium, testes, developmental, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal epithelium and testes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of epithelium related diseases. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e.
nevi, moles, WO 99/22243 PCTIUS9$122376 freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. Moreover, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Furthermore, the tissue distribution also indicates that the protein product of this gene is useful for the treatment and diagnosis of conditions concerning proper testicular function (e.g. endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence. This gene product is also useful in assays designed to identify binding agents as such agents {antagonists) are useful as male contraceptive agents.
Similarly, the protein is believed to by useful in the treatment and/or diagnosis of testicular cancer.
The testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:70. and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 926 of SEQ ID N0:70, b is an integer of 15 to 940, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:70, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 61 When tested against both U937 Myeloid cell and Jurkat T-cell cell lines, supernatants removed from cells containing this gene activated the GAS assay.
Thus, it is likely that this gene activates both T-cells and myeloid cells through the Jak-STAT
S signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT
pathway.
The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT
pathway, reflected by the binding of the GAS element, can be used to indicate proteins i0 involved in the proliferation and differentiation of cells.
This gene is expressed primarily in human adult lymph node and in early stage human lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 15 biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders, lymphatitis and pulmonary disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system 20 and respiratory system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue 25 or bodily fluid from an individual not having the disorder.
The tissue distribution in adult lymph indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases relating to the immune system and respiratory system. Furthermore, expression of this gene product in lymph nodes indicates a role in the regulation of the 30 proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, 35 as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. The biological activity data supports the notion that the translation product of this gene is an activator of various cells of the immune system, and thus could play an important role in the activities of the immune system.
Many polynucieotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:71 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1089 of SEQ ID N0:71, b is an integer of 15 to 1 I03, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:71, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 62 This gene is expressed primarily in glioblastoma and anergic T-cell.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural and immune disorders, such as glioblastosis cerebri.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS and immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, neural, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders relating to the CNS and the immune system. Furthermore, expression of this gene product in T-cells indicates a role in the regulation of the proliferation; survival;
differentiation;
5 and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against 10 the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion 1 S of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available 20 and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:72 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more 25 polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 885 of SEQ ID N0:72, b is an integer of 15 to 899, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:72, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 63 One embodiment of this gene comprises polypeptides of the following amino acid sequence:
CLAEAVSVIQSIPIFNETGRFSFTLPYPVKIKVRFSFFLQIYLIMIFLGLYINFRHLY
KQRRRRYGQKKKRSTKKKDLDGFLPV (SEQ ID N0:365). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in keratinocytes and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, integumentary, or neurological and behavioural disorders.
Similarly, polypeptides. and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the nervous systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntinton's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. Alternatively, expression within keratinocytes indicates polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:73 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 535 of SEQ ID N0:73, b is an integer of 15 to 549, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:73, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 64 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
LCSTPVPTLFCPRIVLEVLV VLRSISEQCRRVSSQVTVASELRHRQWVERTLRSR
QRQNYLR (SEQ ID N0:366). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in osteoclastoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skeletal disorders, and diseases of the haemopoietic and immune system, particularly cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bones, immune and haemopoietic system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.skeletal,hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:223 as residues: Ser-59 to Glu-67.
The tissue distribution in osteoclastoma tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatement and diagnosis of disorders of the bones, immune and haemopoietic systems and cancer. Moreover, the protein may play a role as a therapeutic in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders. For example, in rheumatoid arthritis. lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:74 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 576 of SEQ ID N0:74, b is an integer of 15 to 590, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:74, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 65 When tested against dermal fibroblast cell lines, supernatants removed from cells containing this gene activated the EGR 1 (early growth response gene 1 ) promoter element. Thus, it is likely that this gene activates fibroblast cells through the EGRI
signal transduction pathway. EGR I is a separate signal transduction pathway from Jak-STAT, genes containing the EGR1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
ARGETAYDGAAVEFQEPLSSCLFSSLNPHHWPTLGVGRPVMLTLEDKD (SEQ
ID N0:367), ELLQCQMLEASTLIHLHHPRPGFPALCSFLGFRHHLHHDALCIRV
LPEDLEAKLCVSLHQLLHRGLCLPGFGAACPGDQGSEDEARPPAVLRAVALLR
AGLRHLSVHSGWYHLPH SRNGLPLLALVVHFPEYGGGPREPVPGQSG
EFGRRTELSTKGDTGDSRNSHLAQDMASLPFFKPCECTHV AVCSPPHPLCQ
YLCL (SEQ ID N0:368), LQCQMLEASTLIHLHHPRPGFPALCSFL (SEQ ID
N0:369), HQLLHRGLCLPGFGAACPGDQGSEDEARPPA (SEQ ID N0:370), andlor LALVVHFPEYGGGPREPVPGQSGEFGR (SEQ ID N0:371) .
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, male reproductive and endocrine disorders, cancer, particularly testicular cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive and endocrine systems. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, testes, endcrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:224 as residues: Lys-53 to Leu-60, Pro-94 to Gln-99, Ser-176 to Gly-184, Ser-199 to Val-207.
The tissue distribution in testes, combined with the detected EGRI biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of male reproductive and endocrine disorders, including aberrant testicular function (e.g. endocrine function, sperm maturation).
Moreover, in light of the EGR1 activity, it may also be useful in the diagnosis and treatment of a variety of proliferative disorders, especially testicular cancer. Protein, as WO 99/22243 PCT/US98/2237b well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
5 ID N0:75 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of 10 a-b, where a is any integer between 1 to 1042 of SEQ ID N0:75, b is an integer of 15 to 1056, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:75, and where b is greater than or equal to a + 14.
15 FEATURES OF PROTEIN ENCODED BY GENE NO: bb In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: QSWTAPAARLPMALPQMCDGSHLASTLRYC (SEQ ID
N0:372), QSAAQWFWWPGRSASLGGAKGMQPPSLASWPXPRSIRCL RAPAPC
ESCRTPKVVDI PTYEEAVSFPVAEGPPTPPAYPTEEALEPSGSRDALLSTQPA
WPPPSYESISLALDAVSAETTPSATRSC SGLVQTARGGS (SEQ ID N0:373), GSTGLWRGDRGPIEGGPGMLAL TDHSRVSFPVAEGPPTPPAYPTEEAL
EPSGSRDALLSSVXGASWPGWAVASPSLHQAKQSVPATRTTVPLTVM Q (SEQ
25 ID N0:374), QWFWWPGRSASLGGAKGMQPPSLASWP (SEQ ID N0:375), SSAA
VQVACCCSLACCGPSRPASQGHLRW (SEQ ID N0:376). VSFPVAEGPPTPPAYP
TEEALEPSGSRDALLS (SEQ ID N0:377), and/or RVSFPVAEGPPTPPAYPTEE
ALEPSG (SEQ ID N0:378). Polynucleotides encoding these polypeptides are also encompassed by the invention.
30 This gene is expressed primarily in pituitary gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine disorders, such as dwarfism. Similarly, polypeptides and 35 antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endocrine, immune, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in pituitary indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders of the pituitary gland and endocrine system. Moreover, considering the vital importance of the pituitary in serving as a master regulator for various endocrine glands, the protein product of this gene would also be useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g.
hyper-,hypoparathyroidism) , hypothallamus, and testes. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:76 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 916 of SEQ ID N0:76, b is an integer of 15 to 930, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:76, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 67 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
SNEILLSFPQNYYIQWLNGSLIHGLWNLASLFSNLCLFVLMPFAFFFLESEGFA
GLKKGIRARILETLVM LLLLALLILGIVWVASALIDNDAAS (SEQ ID N0:379).
Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclased cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
This gene is expressed primarily in the developing brain, liver and heart,and to a lesser extent, in cancerous tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental,neural, hepatic, or cardiopulmonary and haemopietic disorders, in addition to cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the fetal tissues and the haemopoietic and neural systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, neural, hematopoietic, hepatic, cardiovascular, pulmonary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, bile, serum, pulmponary surfactant or sputum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:226 as residues: Glu-67 to Asn-74, Glu-88 to Asn-93, Lys-95 to Ser-105, Arg-to Ala-164. Ala-204 to Arg-210, Phe-254 to Thr-262, Pro-295 to His-311.
The tissue distribution in developing brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of haemopoietic and developmental diseases and cancers. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Alternatively, the relatively specific expression of this gene product during embryogenesis indicates that it may be a key player in the proliferation, maintenance, and/or differentiation of various cell types during development. It may also act as a morphogen to control cell and tissue type specification. Because of potential roles in proliferation and differentiation, this gene product may have applications in the adult for tissue regeneration and the treatment of cancers, which include, but are not limited to the following tissues or cells: pulmonary, immune, neural, hematopoietic, or hepatic tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:77 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 4449 of SEQ ID N0:77, b is an integer of 15 to 4463, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:77, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 68 The translation product of this gene shares sequence homology with a putative yeast transmembrane protein which may play an important role in intercellular signalling, intracellular transport, or regulation of cellular homeostasis. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: PTRPVLLLAINGVTECFTFAAMSKEEVDRYNFV (SEQ ID N0:380), andlor NDKKLLFLKGFWSSLKNETPPPHFRLRMVTGVSCSGTLWCLISGV
AVTPLQSPQWG SYTECVPPTELPIAGPGASGVQASLKSRHFVSASGHT (SEQ ID
N0:381 ). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in pulmonary, immune cells, epididymus, and testis tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the reproductive organs, immune, and pulmonary systems, in addition to endothelial and epithelial tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, respiratory and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.pulmonary, immune, reproductive, testes, epididymus, endothelial, epithelial, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, seminal fluid, pulmonary surfactant or sputum, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:227 as residues: Arg-45 to Thr-52, Tyr-60 to Gly-66, Ala-87 to Trp-92, Leu-to Ser-115.
The tissue distribution and homology to putative transmembrane protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases of the reproductive, pulmonary and immune system. Moreover, the protein product of this gene may be useful in the diagnosis, treatment, and/or prevention of a variety of male reproductive disorders, which include.
but are not limited to, aberrant testicular function, male sterility, impotence, or related endocrine disorders. Protein may also serve a role as a contraceptive.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:78 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 777 of SEQ ID N0:78, b is an integer of 15 to 791, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:78, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 69 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
SENRIYRNGLEKMRREVTIGRSSSICLDQQVKAGNAVHHQWLKYVCWMVVVV
GGSGVGDGG NLGM (SEQ ID N0:382). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in PMA induced T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, such as inflammatory or immunodeficiency conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:228 as residues: Ser-62 to Thr-73, Phe-80 to Gln-88.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and diagnosis of immune system disorders. More specifically, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis. granulomatous disease. inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:79 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1278 of SEQ ID NO:79, b is an integer of 15 to 1292, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:79, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 70 This gene is expressed primarily in monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, which include, but are not limited to, leukemias, lymphomas, AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system. expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in monocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of S immune disorders including: leukemias, lymphomas, immunodeficiencies {e.g.
AIDS), immuno-supressive conditions (transplantation) and hematopoietic disorders. In addition this gene product may be applicable in conditions of general microbial infection, inflammation or cancer. Moreover, this gene may also be useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:80 and may have been publicly available prior to conception of the present invention.~Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1269 of SEQ ID N0:80, b is an integer of 15 to 1283, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:80, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 71 When tested against dermal fibroblast cell lines, supernatants removed from cells containing this gene activated the EGR 1 (early growth response gene 1 ) promoter element. Thus, it is likely that this gene activates fibroblast cells through the EGR1 signal transduction pathway. EGRI is a separate signal transduction pathway from Jak-STAT, genes containing the EGR1 promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
NWSGRRLRMWPSAALSPAVSSPALALTSPPKPLKGEVWLRWKLLGSRAVGLF
AF IALGTQSPLLHRACLPVRQSWGCSEHKAYPILRLQPDLETQVGPGHGVN
WDLRTQIRTIGELGGDGGCSE MRPLF (SEQ ID N0:383), and/or NLFSTPCKRQ
KLIKLEWTEAPNVALRCSLSCSLIPGLSPDLSSEAPEGRSVAKMEIARQQSCWL
VCI YCFRNPESTLAPGLPACEAELGLLRAQGLPHPASPARLGNTGGAWPR
SKLGSQNTN {SEQ ID N0:384), SSPALALTSPPKPLKGEVWLRWKLLG (SEQ
ID N0:385), EHKAYPIi.,RLQPDLETQVGPGHGVNWDL (SEQ ID N0:386), andlor ALRCSLSCSLIPGLSPDLSSEAPEGRSV (SEQ ID N0:387). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 11. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11.
This gene is expressed primarily in placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental anomalies, fetal deficiencies, pre-natal disorders and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, placental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:230 as residues: Gly-22 to Gly-29, Gln-37 to Ala-44.
The tissue distribution in placental tissue, combined with the detected EGR 1 biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of developmental anomalies, fetal deficiencies and pre-natal disorders. In addition it may be useful in the detection and treatment of ovarian and endometrial cancers. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:81 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 694 of SEQ ID N0:81, b is an integer of 15 to 708, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:81, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 72 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
LAPECCCGSVTYPRALVPRPCCPEPRAPLQLTLGLFSANPVNASPWGRCRSRR
GRGNLPLGHPVSTAFSSGDS (SEQ ID N0:388), and/or NTLHSKLVPSVYHSTE
KSCLV CFGMCPSIYKKMKSVLLIGTRMLLWLSHISQGPRPEAVLPRAPSP
SAAHPWLVFRKPGKRKPLGQMQKQK REGKPASGSPC (SEQ ID N0:389), YPR
ALVPRPCCPEPRAPLQLTLGLF (SEQ ID N0:390j, and/or VL~IGTRMLL
WLSHISQGPRPEAVLPR (SEQ ID N0:391 ). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
This gene is expressed primarily in infant brain, and to a lesser extent, in placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells. particularly of the developmental and neurological systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, developmental, neural, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:231 as residues: Thr-45 to Arg-50.
The tissue distribution in fetal brain and placenta indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis and treatment of various developmental and neurological disorders and diseases.
The protein product of this gene is useful for the detection/treatment of neurodegenerative disease states. behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis. demyelinating diseases, peripheral neuropathies. neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages. schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or imrnunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:82 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1450 of SEQ ID N0:82, b is an integer of 15 to 1464, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:82, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 73 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
WIIVMFGKVLKIKDFMSTYSHTYTHTHMHAHTHTHTLTLSLLQNVLTLVAISDS
DK ALLIF (SEQ ID N0:392), MTLLIAEKTWRRPWPCQWGYLGAEGDRHLEG
RSLSLRHLQGAETPVLNPDLQLPSHIGKQAWSH ALGSL (SEQ ID N0:393), MSTYSHTYTHTHMHAHTHTHTLTLSLL (SEQ ID N0:394), and/or GAEGDRHLE
GRSLSLRHLQGAET (SEQ ID N0:395). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in the spleen of patients with lymphocytic leukemia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, lymphocytic leukemia and other cancers, as well as immune disorders such as AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spleen tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of lymphocytic leukemia and other cancers, as well as other immune disorders and conditions including, AIDS, arthritis, asthma and microbial infection.
Furthermore, the protein product of this gene may be useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:83 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 602 of SEQ ID N0:83, b is an integer of 15 to 616, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:83, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 74 When tested against Jurket and fibroblast cell lines, supernatants removed from cells containing this gene activated both the GAS (gamma activating sequence), and the EGR1 (early growth response gene 1) promoter elements. Thus, it is likely that this gene activates immune or fibroblast cells through the JAK-STAT and/or EGR 1 signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. EGR1 is a separate signal transduction pathway from Jak-STAT, genes containing the EGRI promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VVEPGLKASLGA
MSTLFPSLFPRVTETLWFNLDRPCVEETELQQQEQQHQAWLQSIAEKDNNLVPI
GKPASEHYDDEEEEDD EDDEDSEEDSEDDEDMQDMDEMNDYNESPDDGEVN
EVDMEGNEQDQDQWMI (SEQ ID N0:396), LFPRVTETLWFNLDRPCVEETEL
(SEQ ID N0:397), and/or YNESPDDGEVNEVDMEGNEQDQD {SEQ ID N0:398).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
The gene encoding the disclosed cDNA is believed to reside on chromosome 11.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11.
This gene is expressed primarily in cells of the immune and haemopoietic I S systems, and to a lesser extent, in several other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and haemopoietic disorders, such as multiple myeloma, immunodeficiencies, and inflammatory conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and haemopoietic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.> cancerous and wounded tissues) or bodily fluids (e.g.lymph.
serum, plasma, urine; synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:233 as residues: Pro-21 to Gly-30.
The tissue distribution in immune tissues and cells, combined with the detected GAS and EGR1 biological acitivity indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune, haemopoietic, and integumentary systems. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lyrnphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:84 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 914 of SEQ ID N0:84, b is an integer of 15 to 928, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:84, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED. BY GENE NO: 75 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: MGFDIHGVLGEAVAEPREKKQE RAKWAPHDYDDPSLS
LQDLLISWMISTWLIPMWKCQATIWFSLIQRLLNAYCMPGNFRHWEIAANTTN
KT PGLMDFKFL (SEQ ID N0:399), EPREKKQERAKWAPHDYDDPSLSLQDL
(SEQ ID N0:400), and/or MPGNFRHWEIAANTTNKT PGLMDF (SEQ ID N0:401).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
The gene encoding the disclosed cDNA is believed to reside on the X
chromosome.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for the X chromosome.
This gene is expressed primarily in fetal liver and spleen, and to a lesser extent, in prostate cancer and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental, reproductive, immune, and haemopoietic disorders Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and developing systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, hepatic, reproductive, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g. lymph, amniotic fluid, serum, bile, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in developing and immune tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of disorders of the haemopoietic and developing immune systems.
In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution.
radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in iymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
Moreover, the expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. The protein may also show utility in the treatment or diagnosis of various hepatic or reproductive disorders, which include, but are not limited to hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells, and prostate cancer, and/or congenital defects such as X-linked conditions. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Sorne of these sequences are related to SEQ
ID N0:85 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 709 of SEQ ID N0:85, b is an integer of 15 to 723, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:85, and where b is greater than or equal to a + 14 FEATURES OF PROTEIN ENCODED BY GENE NO: 76 This gene is expressed primarily in fetal spleen and Wilm's tumor.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, haemopoietic, immune, developmental, or renal disorders, such as congenital defects, mutliple myeloma, or Wilm's tumor. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the haemopoietic and developing systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, immune, hematopoietic, renal, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the haemopoietic and developing systems and cancer. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukenua since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. The expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:86 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 556 of SEQ ID N0:86, b is an integer of 15 to 570, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:86, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 77 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the (gamma activating sequence ~ promoter element. Thus.
it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in induced T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and inflammatory diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids {e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune and inflammatory diseases.
The secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferationldifferentiation modulating activity or induction of other cytokines;
immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy);
regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy);
stimulation or growth of bone, cartilage, tendons, ligaments andlor nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone {for control of fertility);
chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases;
for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:87 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 625 of SEQ ID N0:87, b is an integer of 15 to 639, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:87, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 78 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: QSVPSPPLAPPLPPSLPSFLFTETRSHYVARLVSNSWAQM
ILLPWPLKVLGLDVSHCAWPKSVFLQAMEEIADFCLFSVKYQVSSMTCF DRT
SYMKNTYL (SEQ ID N0:402), and/or LFTETRSHYVARLVSNSWAQMILLPWP
(SEQ ID N0:403). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in bone marrow.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. anemias (leukemias), immune deficiencies and other hematopoietic-related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune. hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in bone marrow indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of hematopoietic and immune disorders, which include, but are not limited to the following: leukemias, lymphomas, auto-immunities, immunodeficiencies (e.g.
AIDS), immuno-supressive conditions (transplantation) and other hematopoeitic disorders, such as multiple myeloma. In addition this gene product may be applicable in conditions of general microbial infection, inflammation or cancer. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:88 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 694 of SEQ ID N0:88, b is an integer of 15 to 708, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:88, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 79 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
SQIKSEKKHIGKAYTCTQTQSTGMQSTLTI V AKKKSRNHTESYTRKKQENQIV
LIPWHQKKHPEGTHTCSHSLRRDTNTAADTQRKIRAHRYTYRRDKYSDTLVTH
DHYKGDKHPSNTHTQPR XEFLQPGGSTNSRAAAPRXSSSFCPFS EGYS
SWGYH (SEQ ID NO:404),GMQSTLTIVAKKKSRNHTESYTRKKQ (SEQ ID
N0:405), KKHPEGTHTCSHSLRRDTNTAADT (SEQ ID N0:406), and/or RRDKY
SDTLVTHDHYKGDKHPSNT (SEQ ID N0:407). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders, such as leukemias, lymphomas, AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:238 as residues: Asp-38 to Leu-43.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders including leukemias, lymphomas, AIDS, arthritis and asthma, as well as other conditions which potentially implicate the immune system, such as atherosclerosis, cancer and infection. In addition, This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity: immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:89 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 935 of SEQ ID NO:89, b is an integer of 15 to 949, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:89, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 80 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: KHLPLKAPIDLDNKNSCMFCSRDIFCRFH HSTAWLFL
GRTTDRILGLHHYLIRYQFEIENLCLMKIVIPV VSMKTNCQFDFLGQLKQNLYH
(SEQ ID N0:408), APIDLDNKNSCMFCSRDIFCR (SEQ ID N0:410), and/or IENLCLMKIVIPVVSMKTNCQFDFLGQL (SEQ ID N0:409). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in prostate carcinoma cell line stimulated with 30 nM synthetic androgen, 81881 cells and, to a lesser extent, in activated monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. reproductive or immune disorders, particularly prostate cancer and prostate ailments. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, seminal fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in the prostate indicates that polynucleotides and polypeptides corresponding to this gene are useful for the disgnosis and intervention of prostate cancer and prostate ailments, or related proliferative conditions in either said tissue or other tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:90 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1157 of SEQ ID N0:90, b is an integer of 15 to 1171, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:90, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 81 The translation product of this gene shares strong sequence homology with human protocadherin 42 (GenBank accession no. gi1387675), PCDH7 (BH-Pcdh)a, and its associated isoforms PCDH7 (BH-Pcdh)b, and PCDH7 (BH-Pcdh)c which are thought to be important in tissue and cell-cell adhesion, repair and development (See Genbank Accession Nos.gnlIPIDId1026122 (AB006755), gnIIPIDId1026123 (AB006756), and gnlIPIDId1026124 (AB006757)). The polynucleotides encoding this gene have been gened by another group subsequent to our filing {See Yoshida K, et al, Genomics 1998 May 1;49(3):458-61, which is hereby incorporated by reference).
The cytoplasmic domain of cadherin interacts with the cytoskeleton through catenins and other cytoskeleton associated proteins. The cytoplasmic domain is not present in all cadherins, but in those which possess it, it is essential for the cadherins adhesive function. The cadherins which do not possess a cytoplasmic domain appear to function via a different method from those with a cytoplasmic domain. This protein sequence is involved in cell-cell adhesion. This sequence may have regulatory functions in the cell, as well as the cell-cell adhesive properties. Antibodies produced against this sequence are useful for modulating the binding activity of protocadherins, and can be used therapeutically. BH-Pcdh has an extracellular domain consisting of seven repeats of the cadherin motif (EC 1 to 7). EC2 of BH-Pcdh is unique in having a 55-amino-acid insertion in the middle of the motif. There are three isoforms of BH-Pcdh, denoted -a, b, and -c, which have different cytoplasmic tails and a 47-amino-acid deletion in the EC2-3 region of BH-Pcdh-c. While only a 9.0-kb message was detected in normal tissues, 4.5- and 9.0-kb mRNA species were seen in the human lung carcinoma cell line A549. Furthermore, only the 4.5-kb mRNA was detected in HeLa cell S3 and WO 99122243 PCT/US98/2237b human gastric cancer cell lines MKN28 and KATO-III. Southern blot analysis indicated that the BH-Pcdh gene is likely to be conserved among various vertebrates. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GTSVNESVSNATAIDSQIARSLHIPLTQDIAGDPSYEISKQRLSIVIGVVAGI (SEQ
ID NO:411), PKIKMAMKPAKKITKTFLHPNSMTNLKSLKRTRKTKNLSSLSTA
ALSLWRLLSQMDRGMIVSMRSCQTAQ AWGDTGPLMVGPAVLTWQGITNL
VPHCLLFSFIPSHQLQEKNTRPYKIYHQPTHLWEQETTFQLDQITAL STAVKP
ITSTANRCVYIHTLLCLAEFHSNMMLHYAPYCDDLSTPKPAGACPWPWGVSQS
LLVPLVVHFIF ESFSFSYTEK (SEQ ID N0:412), CSIMHHTVMTFLLRNLLEPA
LGRGVSANHCLFHLLYILFL SLFLSHIQKNSMKIK (SEQ ID N0:413), TAIDS
QIARSLHIPLTQDIAGDPSYEISK (SEQ ID N0:414), YCRSKNKNGYEAGKKDH
EDFF (SEQ ID N0:415), GPGSPDLARHYKSSSPLPTVQ (SEQ ID N0:416), and/or LPPANTFVGAGDNISIGSDHCSEYS (SEQ ID N0:417). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 4. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4.
This gene is expressed primarily in ovarian tumor, and to a lesser extent in, striatum and HL-60 cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer and reproductive dysfunction, in addition to cardiovascular and neural disorders,such as atherosclerosis, and neurodegenerative disorders, such as Alzheimer's and Parkinson's, or other disorders resulting from aberrant cell-adhesion.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive, nervous and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, neural, cardiovascular, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:240 as residues: Tyr-15 to Leu-59, Ala-68 to Asp-85, Pro-87 to Asn-96, His-to Lys-129, Ser-153 to Gln-170.
The tissue distribution in ovarian and muscle tissue, combined with the strong homology to various cadherins indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, study and treatment of various neoplastic disorders such as squamous cell carcinomas and related tumors, and nervous system and reproductive disorders. Considering the vital importance of cell-adhesion amongst various cellular functions, in particular chemotaxis by the immune and hematopoietic cells indicates that this gene product may play a direct, or in-direct role in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Furthermore, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also play an in-direct role in the regulation of a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines;
immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy);
regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy);
stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility);
chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases;
for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:91 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucieotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1137 of SEQ ID N0:91, b is an integer of 15 to 1151, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:91, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 82 The translation product of this gene shares sequence homology with the G-protein coupled receptor TM3 consensus polypeptide which may implicate an important function for this protein in various signal transduction pathways. G-protein coupled receptors are known to have a variety of functions including modulating immune system tissue through interaction with cytokines and lymphokines. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GTSNAS VSPTICICMCGYVHIWFFICLCVYLKVLQGSACPWIAAAV VMRRMRK
VQEKGEVFRNMAATWAL RSGIQSLNSLVSSAFFTIFMTLGSSWNLIVSLSSLV
NWTGLFSFYFSRN (SEQ ID N0:418), CLCVYLKVLQGSACPWIAAAVV
MRRMRK (SEQ ID N0:419), and/or TIFMTLGSSWNLIVSLSSLVNWTGLF (SEQ
ID N0:420). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in breast lymph node.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, breast cancer, or other immune or reproductive disorders and diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, reproductive, breast, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, breast milk, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:241 as residues: Cys-34 to Gly-48.
The tissue distribution in breast lymph nodes and homology to a conserved G-protein coupled receptor TM3 consensus sequence indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for breast cancer or immune diseases. Considering the vast roles which G-protein coupled receptors play in the maintenance of important cellular fuctions, the secreted protein may have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines;
immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy);
regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy);
stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility);
chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity {e.g. for treating septic shock, Crohn's disease}; as antimicrobials; for treating psoriasis or other hyperproliferative diseases;
for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Furthermore, the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements.Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:92 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 700 of SEQ ID NO:92, b is an integer of 15 to 714, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:92, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 83 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
QPDIPVLPVGFSQNCSFKVSGCWKGGLIAEKVGTLGTPKGRR AWPETEF
FRFLEPGLP (SEQ ID N0:421), and/or RGFRMAQPLVNTFQVAVPVEDL
APQQNPSRFPADPALLSFLTG SILAPGKVIWVNVSFTAIIWPTWDSMAI
GELTIASHASMTLHIGRPGSRKRKNSVSGHARLPFGVPSVPT FSAISPP
FQQPETLKEQF (SEQ ID N0:422), EDLAPQQNPSRFPADPALLSFLTG (SEQ ID
N0:423), and/or TWDSMAIGELTIASHASMTLH1GRPGSRK (SEQ ID N0:424).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in activated T-cells, hepatocellular tumor, pancreas islet cell tumors, and hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hepatic, and endocrine disorders, such as cancers, particularly of T-cells, hepatocellular tumors and pancreas islet cell tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hepatic, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, bile, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:242 as residues: Glu-43 to Lys-50, Ser-53 to Phe-60.
The tissue distribution in T-cells, hepatocellular tumors, and pancreatic islet cell tumors indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of immune, hepatic, and endocrine disorders, and other cancer types. Expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders in various tissues, aside from those disclosed above. Similarly, developmental tissues rely on decisions involving cell differentiation andlor apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:93 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 796 of SEQ ID N0:93, b is an integer of 15 to 810, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:93, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 84 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
VSPQLMGIKREPSAAQLSVGEEHTLDREGRELVDLPGQPSQKIKIKNKSSLHPG
LAPP AHYKTATTTNLF (SEQ ID N0:425), and/or PSAAQLSVGEEHTLDREGREL
(SEQ ID N0:426). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in hepatocellular tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hepatic disorders, such as liver diseases and hepatocellular tumor, including proliferative disorders in other tissues and cell types. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.hepatic, proliferating, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, bile, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in hepatocellular tumor tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of hepatocellular tumor or other liver disorders.
Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:94 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1162 of SEQ ID N0:94, b is an integer of 15 to 1176, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:94, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 85 When tested against reh cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus. it is likely that this gene activates B-cells through the JAK-STAT signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: NCDHDFIQPLHTPMSAL FQSEFS (SEQ ID N0:427), SILNM
GLFTEQRPWPAAARCARQSTVAGAIRRARGTVTMWQVAGAAW ASPDRRAKV
HPCRHAAPCLPSPCRRGLQMSGPLQATRGRVTLRSHQVGCKRATGSTENSL
(SEQ ID N0:428), QKSKGSPLQTCCSLPTLPMQERPADEWSTPGDQGKSYIK
KPPGGLQKGHRLHRKLTLKQGRHRGVE GLNEIMVTVLKEEFPVSKPGLNV
LPTFHRHHECYQHGMNLTARISVVS {SEQ ID N0:429), ARQSTVAGAIRR
ARGTVTMWQVAGA (SEQ ID N0:430), PCRRGLQMSGPLQATRGRVTLRSHQ
(SEQ ID N0:431 ), LPMQERPADEWSTPGDQGKSYIKKPP (SEQ ID N0:432), and/or NVLPTFHRHHECYQHGMNLTARI (SEQ ID N0:433). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human fetal kidney, adult testis, T-cell lymphoma, and a fetal liver/spleen cDNA library.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, renal, developmental, reproductive, immune, or hematopoietic disorders, particularly kidney disease, lymphoma, congenital defects, multiple myeloma, SCID, male sterility, and cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the kidney and immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoeitic, reproductive, renal, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:244 as residues: Gly-35 to Gly-40.
WO 99122243 PCT/US98l22376 The tissue distribution in fetal kidney and T-cells, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatement of kidney diseases or immune disorders, especially cancers. Specifically, this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
Similarly, developmental tissues rely on decisions involving cell differentiation andlor apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:95 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To Iist every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1014 of SEQ ID N0:95, b is an integer of 15 to 1028, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:95, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 86 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in breast, human embryo, and chronic spleen lymphocytic leukemia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive, developmental, hematopoietic or immune disorders, such as breast cancer, congenital birth defects, or leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the breast or hematopoietic systems, expression of this gene at significantly higher or lower levels may be detected in certain IS tissues or cell types (e.g.reproductive, immune, hematopoietic, developmental, breast, and cancerous and wounded tissues) or bodily fluids {e.g.lymph, amniotic fluid, breast milk, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:245 as residues: His-2 to Asn-$, Gln-35 to Phe-44.
The tissue distribution in breast and lymphocytic leukemia cells, combined with the detected GAS biological activity indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or intervention of breast cancer, leukemia or other hematopoietic related disorders. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies WO 99/22243 PCT/US9$/22376 directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:96 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 733 of SEQ ID N0:96, b is an integer of 15 to 74?, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:96, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 87 This gene is expressed primarily in brain containing medulla blastoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, particularly specific brain tumors such as medulla blastoma, as well as other diseases and conditions of the brain. such as schizophrenia, Alzheimer's disease, Tourette's syndrome, Parkinson's disease, Huntington's disease.
mania, dementia, paranoia, depressive and addictive predispositions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of specific brain tumors such as medulla blastoma. In addition it may also be useful for the diagnosis and treatment of developmental, degenerative and behavioral conditions of the WO 99122243 PCT/US9$/2Z376 brain and nervous system, such as schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, mania, dementia, paranoia, addictive behavior, obsessive-compulsive and sleep disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:97 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 614 of SEQ ID N0:97, b is an integer of 15 to 628, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:97, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 88 When tested against Jurket cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates T-cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: INVLYCSRDSLMGRTIMESSDYIKKGANVSPVLGVRQQ AV
(SEQ ID N0:434). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adrenal gland tumor and T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the endocrine and immune or haemopoietic systems, particularly inflammatory or immunodeficiency conditions. such as AIDS.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and endocrine systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types {e.g.immune, hematopoietic, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells and adrenal gland tissues, combined with the detected GAS biological activitiy indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune and endocrine systems and cancer. Moreover, the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities.
Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotaetic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease); as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:98 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 890 of SEQ ID N0:98, b is an integer of 15 to 904, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:98, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 89 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: SLLMYFVFKIFFQSLCVLGYCILPLTVA (SEQ ID N0:435).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a IS biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:248 as residues: Thr-43 to Thr-48.
The tissue distribution in dendritic cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune system disorders. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stern cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:99 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 562 of SEQ ID N0:99, b is an integer of I 5 to 576, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:99, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 90 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
RLWMTKAHPALRHLLLLFTLALTLLAQGCCAVAPSGCADLAGFCSLGHS C
(SEQ ID N0:436). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human stomach.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, digestive and gastrointestinal conditions, particularly ulcers and cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.gastrointestinal, metabolic, mucosal, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, chyme, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:249 as residues: Pro-32 to Gly-38.
S The tissue distribution in stomach tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of gastrointestinal disorders, or other disorders afflicting mucosal or endothelial tissues.
Protein, as well as, antibodies directed against the protein rnay show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:100 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 699 of SEQ ID NO:100, b is an integer of 15 to 713, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:100, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 91 The translation product of this gene was found to have homology to the conserved K07F5.14 protein from Caenorhabditis elegans (See Genbank Accession No gnllPIDle233697) which may be important in regulation of important cellular functions, including homeostasis and cell division. When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) pathway. Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
RTCTPWMGFWCLVCSLFAPVPTSRKYLVSKPGCYQRRRV FGVCFTKPL (SEQ
ID N0:437), WLLSEKKG (SEQ ID N0:438), and/or GVFYKAAVIG (SEQ ID
N0:439). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in bone marrow and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune or hematopoietic disorders, particularly multiple myeloma, immunodeficiencies, and cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and endocrine systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in bone marrow and T-cells, combined with the detected GAS biological activity in U937 cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of immune and hormonal disorders and neoplasias. Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Moreover, the protein may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoirnmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation andlor proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:101 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of I S a-b, where a is any integer between I to 635 of SEQ ID NO: l0 i , b is an integer of 15 to 649, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:101, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 92 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
CKTSPLPKEGQSAVSVPVSSHFLAHSAPLSGGHAHVFARDGATGL (SEQ ID
N0:440), LGRGSGERKTPVSCFAQISKSRGGRSKSLTHLCTHTHTQVTEL
DVRMSHGCLRXQHAGRLAPPPPLRFCL TACWGRRGEAETVWKDPASSQ
HPPPSEKPHRQDRHPERWHQPGGPIPGKHMRVSPGQRGRVCQEMGRNRN
(SEQ ID N0:441 ), FCLRDFKIWRGRLEAGRTEGRL AGERFGGEEDPSFLFC
SDFKVEGWAFEISHSLVHTHTHTGHGAGRADVTRVPAGTARWEAGSPTPSPV
LF DSLLGAAGRG (SEQ ID N0:442), AQISKSRGGRSKSLTHLCTHTHTQVTEL
(SEQ ID N0:443), EKPHRQDRHPERWHQPGGPIPGKHMR (SEQ ID N0:444), GRLEAGRTEGRL AGERFGGEEDPSFL (SEQ ID N0:445), and/or VTRVPAGTARWEAGSPTPSPVLF (SEQ ID N0:446). Polynucleotides encoding these polypeptides are also encompassed by the invention.The gene encoding the disclosed cDNA is believed to reside on chromosome 19. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.
This gene is expressed primarily in ovary, spinal cord, and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental, reproductive, and neurological conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nrevous and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, reproductive, ovarian, immune, hematopoeitic, and cancerous and wounded tissues) or bodily fluids (e.g.Iymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily 1 S fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:251 as residues: Pro-34 to Pro-53.
The tissue distribution in spinal cord and fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study and treatment of neural, hematopoietic, and developmental disorders.
Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition. homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia. pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include, but are not limited to bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:102 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 683 of SEQ ID N0:102, b is an integer of 15 to 69?, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:102, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 93 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: DEGVQGERLFRILRINGEKPYNFVDYFHCEY (SEQ ID
N0:447), KVVRIDNGILCSHKKTEIMSLQQHGWIWRPYLKQTNTGTENQIPHTL
TYKWELNFEYIXTQXRGXXDSEAYLKVEGGRREGIQKLPIRYYVYYLGDKIICT
SSSCSMHLLM (SEQ ID N0:448), HKDTCMSMFT AALFTIAKTWN (SEQ ID
N0:449), MPINDRLDFKRWYV (SEQ ID N0:450), TMESYVAIKRQRSCPCSNM
VGSGGHILSKLTQEQKTKYHILS LISGS (SEQ ID N0:45 I ), EIMSLQQHGWIW
RPYLKQTNTGTEN (SEQ ID N0:452), and/or RREGIQKLPIRYYVYYLGDKIICT
(SEQ ID N0:453). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in bladder tissue from a human male.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, gastrointestinal, urogenital, and nephrotic conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal and excretory systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.renal, bladder, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the. standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:252 as residues: Arg-52 to Ala-57, Pro-66 to Thr-72.
The tissue distribution in bladder tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of gastrointestinal and urinary tract disorders.Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:103 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1274 of SEQ ID N0:103, b is an integer of 15 to 1288, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:103, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 94 This gene is expressed primarily in bladder tissue from a human male.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, gastrointestinal, renal, and urinary tract conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the intestinal and urinary tract, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.renal, urogenital, bladder, cancerous and wounded tissues) or bodily fluids (e.g.Iymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in bladder tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of urinary tract and gastrointestinal disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:104 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1013 of SEQ ID N0:104, b is an integer of 15 to 1027, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:104, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 95 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: LHGEQVPI YIFLLMQPLNFECISFLNCIEQYSVGVI HNSV
TIYACDREENCMDIRYL (SEQ ID N0:454), and/or GTSWASRFFTCH (SEQ ID
N0:455). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and inflammatory disorders, particularly immunodeficiencies such as AIDS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:254 as residues: Lys-28 to Thr-34.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune system. Moreover, This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease. inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:105 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 696 of SEQ ID N0:105, b is an integer of 15 to 710, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:105, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 96 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
GPPRXFXPKKAILGXPPXGR VPPFRYRSRNSRGRPHXSAPRV RFCLENS WLR
(SEQ ID N0:456), andlor PLNTMMCMMCKMKVSPKIFSKLKRKYLNSNTLTKL
EMQTVHLESSLASCSPNKSGXVGRTR GVDPGNSGTGT (SEQ ID N0:457).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This Gene is expressed primarily in lymphoma and frontal cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are 1 S not limited to, neurological and haemopoietic diseases, particularly neurodegenerative conditions such as Alzheimers and Parkinsons. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in frontal cortex and lymphoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases of the neural and haemopoietic systems.
Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment S and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
Moreover, the expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Since, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation, this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:106 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 516 of SEQ ID N0:106, b is an integer of I ~
to 530, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:106, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 97 This gene is expressed primarily in the spleen of a patient with metastatic melanoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. immune or hematopoietic disorders, particularly metastatic melanoma and other cancers. as well as immune disorders and conditions such as anemias, AIDS, arthritis and asthma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:256 as residues: Pro-26 to Asn-34.
The tissue distribution in spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of metastatic melanomas and other cancers, as well as other immune disorders and conditions including leukemias, lymphomas, AIDS, arthritis, asthma and microbial infection.
Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, or thrombocytopenia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:107 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 378 of SEQ ID N0:107, b is an integer of 15 to 392, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:107, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 98 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: GTVTQKRK CVFGKYLLSTCSLMFSSMHGACSWKA
KQTSSSAGFLCLHVLCPALQLTREKYKTWPWPSFI (SEQ ID N0:458), and/or MKEGQGHVLYF SRVNCKAGHXTCRQRKPADELVCFAFQEQAPCILLNI
RLQVLNKYLPNTHFLFCVTVP (SEQ ID N0:459). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 8. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 8.
This gene is expressed primarily in pineal gland and synovial sarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine or skeletal disorders, including cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endocrine, pineal, skeletal, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in pineal gland indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the endocrine system. In addition, polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes. Alternatively, the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:108 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 977 of SEQ ID N0:108, b is an integer of 15 to 991, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:108, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 99 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
TMTGIDSSPEEILRQVGCKQQQGKGVEHVEGSSAEAGEAARGGGAK GGGG
AAGKGTSKVGTLRRTRGST (SEQ ID N0:460). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in breast and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the reproductive system and developing organs, particularly congenital defects afflicting the immune or hematopoietic system, such as immunodeficiencies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.reproductive, developing, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:258 as residues: Gly-23 to Asn-30, Ser-37 to Asn-43.
The tissue distribution in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases involving developmental tissues and reproductive organs. The secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions and as nutritional supplements. It may also have a very wide range of biological acitivities. Typical of these are cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anaemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments andlor nerves (e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating haemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's disease}; as antimicrobials; for treating psoriasis or other hyperproliferative diseases; for regulation of metabolism, and behaviour. Also contemplated is the use of the corresponding nucleic acid in gene therapy procedures.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:109 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 898 of SEQ ID N0:109, b is an integer of 15 to 912, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:109, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 100 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
AQREAGSRPRRRKSLKAVAMLXVEMGGGCRGSMGPGPGYSAGSRVCRGSSL
PQVAPFNPSRAHLLPPPVG GGLNSVWLSGVQLSTPPYADWEGVGQSPQ
PRGPWMGSSSLGTVGPGCVLSGCPTVKANGGSPCSEMLGER RLLEPSVG
PVSGCPERREGGHGARGAAGVVVKGHASVQLNFLSLI (SEQ ID N0:461), KAEFTFAKEKNAKAQLGKKGTRW V KHDKRKEIQLYGCVTLNDDPSCPPCPVP
TLPPFWTA TYGSHGRFQKPPFSQHLRAGGAPVGLDCGAPTQYAARPHGPK
(SEQ ID N0:462), GCRGSMGPGPGYSAGSRVCRGSSLPQ (SEQ ID N0:463), QPRGPWMGSSSLGTVGPGCVLS (SEQ ID N0:464), and/or GAAGVVVKGH
ASVQLNFLSLI (SEQ ID N0:465). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in endothelial, immune, and cancer cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases involving immune, endothelial, and haemopoietic tissues or cells, particularly cancers, inflammatory or immunodeficiency conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, haemopoietic and endothelial systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.endothelial, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune and hematopoietic tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders of the immune and haemopoietic systems, including cancer.
More specifically, this gene product may be involved in the regulatic.~~ of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, Tense tissue injury, demyelination, systemic Lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:110 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 861 of SEQ ID NO:110, b is an integer of 15 to 875, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:110, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 101 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: GKPLSAIFPICH MMFLPGKFNLGISHRCCRMT SPWDK
RQQLRQECKSDPHVQNPRIHFPESKNSFPSAYIFVSEGNGVSPSK WHCIY
SGTSLSH (SEQ ID N0:466), andlor GERGRYQSKYSATWMVTPHYLQTQRC
KLREMNSWIQGNEFLDSEHEGQIYIPVSIVDAYPKD (SEQ ID N0:467).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in human kidney, and to a lesser extent, in liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, kidney, urogenital, hepatic, and endocrine disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal or endocrine systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.urogenital, kidney, endocrine, hepatic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, bile, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:260 as residues: Glu-38 to Lys-43.
The tissue distribution in kidney indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of renal disorders, including noninflammatory and inflammatory lesions, and tumors of the kidney.
Moreover,this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Alternatively, expression within liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g.
hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:111 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 445 of SEQ ID NO:11 l, b is an integer of 15 to 459, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: I 11, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 102 This gene is expressed primarily in kidney cortex and fetal tissue.utility_ The tissue distribution in kidney indicates that this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:112 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 595 of SEQ ID N0:112, b is an integer of 15 to 609, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:112, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 103 This gene is expressed primarily in ovary and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, reproductive and neurological conditions, particularly proliferative S disorders, such as ovarian cysts or cancer, in addition to neurodegenerative conditions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, reproductive, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine. synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in ovarian tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of reproductive disorders, such as infertility. Alternatively, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors; including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders; or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO: l I3 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1390 of SEQ ID N0:113, b is an integer of 15 to 1404, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:113, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 104 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ISIRGRIL
YKMAYFKVCVIIWFQQFCVEETSIIKNVRMLTSEFQNSYATPVSGLLPGAVAWR
GGAVYGWVRHAMQVLQ KEPTQPSSFLPPSDAASFWGPESRLHLTW (SEQ ID
N0:468), KPFAFSARNFPTMLSEAYFQDPRMRQHHLGVERMTV AWVPSAIP
AWRASPTRTQHHPSKPQHQEGAQKQGWHMNSGILMSAYEHFL (SEQ ID
N0:469), and/or HSKQNICREVNILKMFLHEIKKTVTDNISTQRRFTYNHQPGS
VSIFSVTDILDFEVPFGL (SEQ ID N0:470). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in melanocytes, and PHA stimulated T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not Iiznited to, immune or integumentary system disorders, and cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.integumentary, immune, hematopoieitc, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in immune cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, diagnosis and treatment of cancers and immune system disorders. Alernatively. the expression in melanocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e. keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:114 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 839 of SEQ ID N0:114, b is an integer of 15 to 853, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:114, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 105 This gene is expressed primarily in B cell lymphoma, and to a lesser. extent, in dermal fibrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or integumentary disorders, particularly lymphatic and soft tissue cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in B-cell lymphoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeftciency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Alternatively, the protein product of this gene may also be useful for the treatment, diagnosis, and/or prevention of various skin disorders including congenital disorders (i.e. nevi, moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome), integumentary tumors (i.e.
keratoses, Bowen's disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's disease, mycosis fungoides, and Kaposi's sarcoma), injuries and inflammation of the skin (i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erytherriatosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma. In addition, such disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm). Moreover, the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie.
spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:115 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 831 of SEQ ID N0:115, b is an integer of 15 to 845, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:115, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 106 When tested against U937 cell lines, supernatants removed from cells containing this gene activated the GAS (gamma activating sequence) promoter element.
Thus, it is likely that this gene activates promyelocytic cells through the JAK-STAT
signal transduction pathway. GAS is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
KVIDVIFSLPPGRKATFSCPLAPLSGAXGLPGGGANRPGPFLPCIQPWGPLRLP
EGC (SEQ ID N0:471), MSSSLCPQGGKPPSLAPWPLCQGPXVCRVGVPT
GLALSSPASSHGGLCDCRKVAWLVPGPAQARG RAAWFYFYLTLFSVL (SEQ
ID N0:472), and/or LALSSPASSHGGLCDCRKVAWLVPGP (SEQ ID NO:473).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in T cells, fetal liver, and to a lesser extent, in various normal and transformed tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hematopoietic, or developmental disorders, including immunodeficiencies and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:265 as residues: Arg-5 to Pro-12.
The tissue distribution in B-cells and fetal liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of immune and developmental disorders. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoetic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. The uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia. The gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. In addition, expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:116 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 746 of SEQ ID N0:116, b is an integer of 15 to 760, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:116, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 107 One embodiment of this gene comprises the following amino acid sequence:
MQRERWARPWMASTVESRMPEGKWRRFSTDLATWGATPARSWTKASRGSTT
AWTRLPMRSTMVLDKQERKQRSLAMGSTTLLDRPGRKQTKRSKGSTLGSTRL
GRKQRNLAKGSTMLLTRLERXWRSLAQVPTMLLARPGRSCRMLIMGSTKPAR
RPTSC (SEQ ID N0:474 ). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in keratinocytes and tissues undergoing wound healing, and to a lesser extent, in osteoblasts and smooth muscle.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, skin disorders; fibrosis; scarring; osteoporosis;
osteopetrosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skin, bone, or connective tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. skin, bone, connective tissues, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:266 as residues: Gly-76 to Leu-83, Ala-108 to Glu-113, Ala-126 to Lys-132, Gly-145 to Leu-151.
The tissue distribution in keratinocytes indicates that polynucleotides and polypeptides con esponding to this gene are useful for the diagnosis and/or treatment of a variety of skin disorders. Elevated expression of this protein in skin and keratinocytes suggest that it may be involved in keratinocyte proliferation, survival, and/or differentiation. Thus, it may play a role in such processes as fibrosis and wound healing. Similarly, expression of this protein in osteoblasts indicates that it may also play a role in osteoblast survival, proliferation, and/or differentiation, and that it may be useful in the treatment of such disorders as osteoporosis or osteopetrosis.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:117 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more poiynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 974 of SEQ ID N0:117, b is an integer of 15 to 988, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:117, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 108 The translation sequence of this gene shares homology with a mouse camodulin binding protein. The calcium-binding regulatory protein calmodulin is an essential subunit of the erythrocyte and other plasma membrane calcium ATPases. A rise in cytosolic calcium induces the binding of calcium ions to calmodulin, which triggers an allosteric activation of the calcium ATPase, and subsequently an export of calcium ions from the cell is accelerated.
This gene is expressed primarily in teratocarcinoma cells, and to a lesser extent, in myeloid progenitor cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental defects, calcium-transport defects, in addition to immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of embryonic and fetal tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
developing tissues, immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:267 as residues: Tyr-124 to Gly-129.
The tissue distribution in teratocarcinoma cells indicates that polynucleotides and polypeptides corresponding to this gene are useful far the diagnosis and treatment of developmental defects as well as for organ regeneration. Moreover, expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Alternatively, the homology of the translation product of this gene to a mouse calmodulin binding protein indicates that the translation product of this gene may be useful for disorders involving calcium transport across the plasma membrane, for example. It has further been suggested this type of disorder may be responsible for disorders such as hypertension.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:118 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1933 of SEQ ID N0:118, b is an integer of 1 S
to 1947, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:118, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 109 One embodiment of this gene comprises polypeptides of the following amino acid sequence:
MRPLLGLLLVFAGCTFALYLLSTRLPRGRRLGSTEEAGGRSLWFPSDLAELREL
SEVLREYRKEHQAYVFLLFCGAYLYKQGFAIPGSSFLNVLAGALFGPWLGLLL
CCVLTS VGATCCYLLSSIFGKQLV VSYFPDKV ALLQRKVEENRNSLFFFLLFLR
LFPMTPNWFLNLSAPILNIPIVQFFFSVLIGLI PYNFICVQTGSILSTLTSLDA
1S LFSWDTVFKLLAIAMVALIPGTLIKKFSQKHLQLNETSTANHIHSRKDT (SEQ ID
N0:47S). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in ovarian tumor, and to a lesser extent, in smooth muscle and breast cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and fox diagnosis of diseases and conditions which include, but are not limited to, cancers, particularly of the ovary, musculature, and breast, such as rhabdomyosarcomas or fibroids. Similarly, polypeptides and antibodies directed to 2S these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
ovaries, breast. cancerous and wounded tissues} or bodily fluids (e.g.lymph, serum, breast milk, plasma, urine, synovial fluid and spinal fluid} or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
3S N0:268 as residues: Arg-24 to Arg-29.
The tissue distribution in ovarian tumor tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer, particularly ovarian and breast cancers. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:119 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1434 of SEQ ID N0:119, b is an integer of 15 to 1448, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:119, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 110 The translation product of this gene shares sequence homology with bovine acrosin inhibitors IIa and IIb which is thought to be important as protease inhibitors.
This gene is expressed primarily in keratinocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, integumentary disorders, such as psoriasis, and wound healing abberations. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the integumental system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:269 as residues: Tyr-39 to Lys-58.
The tissue distribution in keratinocytes, combined with the homology to the bovine acrosin inhibitors IIa and IIb indicates that polynucleotides and polypeptides corresponding to this gene are useful for the acceleration of wound healing.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:120 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 482 of SEQ ID N0:120, b is an integer of 15 to 496, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:12U, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 111 This gene is expressed primarily in fetal liver/spleen, T cells, and to a lesser extent, in bone marrow and primary dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hematopoietic disorders; immune dysfunction; lymphomas.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ 117 N0:270 as residues: Glu-28 to His-34.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of hematopoietic disorders. This gene product is primarily expressed in hematopoietic cells 164.
and tissues, suggesting that it plays a role in the survival, proliferation, and/or differentiation of hematopoieitic lineages. This is particularly supported by the expression of this gene product in fetal liver and bone marrow, the two primary sites of definitive hematopoiesis. Expression of this gene product in T cells and primary dendritic cells also strongly indicates a role for this protein in immune function and immune surveillance. Furthermore, since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO: I21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1160 of SEQ ID N0:121, b is an integer of 15 to I 174, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:121, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 112 The gene encoding the disclosed cDNA is thought to reside on chromosome 14.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 14.
This gene is expressed primarily in fetal liver, spleen, and to a lesser extent in melanocyte.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. developmental, integumentary, or hematopoeitic disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing imtnunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of fetal and embryonic tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:271 as residues: Met-1 to Met-7, Gln-43 to Glu-50, Thr-89 to Thr-95.
The tissue distribution in fetal liver and spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of developmental hematopoeitic disorders. Additionally, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of hematopoietic disorders. This gene product is primarily expressed in hematopoietic cells and tissues, suggesting that it plays a role in the survival, proliferation, and/or differentiation of hematopoieitic lineages.
This is particularly supported by the expression of this gene product in fetal liver, which is a primary sites of definitive hematopoiesis, and strongly suggesting a role for this protein in immune function and inunune surveillance.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:122 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1032 of SEQ ID N0:122, b is an integer of I S
to 1046, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:122, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 113 When tested against Jurkat T-cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates T-cells through the Jak-STAT signal transduction pathway. The gamma activating sequence (GAS) is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway. The Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells.
Therefore, activation of the Jak-STAT pathway. reflected by the binding of the GAS
element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
This gene is expressed primarily in B cell lymphoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, B cell lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:272 as residues: Gln-23 to Asn-31, Tyr-42 to Ser-58.
The tissue distribution in B-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of lymphomas, particularly B cell lymphomas. Furthermore, expression of this gene product in B-cells indicates a role in the regulation of the proliferation; survival;
differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.
In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Additionally, the biological activity data supports the notion that the translational product of this gene activates specific immune cells, and therefore may play a role in the initiation of immune system activity.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:123 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1146 of SEQ ID N0:123, b is an integer of 15 to 1160, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:123, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 114 This gene is expressed primarily in neutrophils: IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of certain immune disorders, especially those involving neutrophils. Expression of this gene product in neutrophils indicates a role in the regulation of the proliferation;
survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation. or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses}.
Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Sorne of these sequences are related to SEQ
ID N0:124 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 879 of SEQ ID N0:124, b is an integer of 15 to 893, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:124, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 115 One embodiment of this gene comprises polpeptides of the following amino acid sequence: DIMPASVIFLICEGVLYGVQG (SEQ ID N0:476). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, placental insufficiency; developmental abnormalities; aberrant angiogenesis; abnormal development and/or maintenance of the placenta.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the placenta and. more generally, the vasculature and/or endothelium, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
developing, placental, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression.level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in placental tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of disorders of the placenta. Specific expression within the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. Alternately, this gene product may be produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus. Expression of this gene product in a vascular-rich tissue such as the placenta also indicates that this gene product may be produced more generally in endothelial cells or within the circulation. In such instances, it may play more generalized roles in vascular function, such as in angiogenesis. It may also be produced in the vasculature and have effects on other cells within the circulation, such as hematopoietic cells. It may serve to promote the proliferation, survival, activation, and/or differentiation of hematopoietic cells, as well as other cells throughout the body.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:125 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1035 of SEQ ID N0:125, b is an integer of 15 to 1049, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:125, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 116 This gene is expressed primarily in keratinocytes, as well as in synovial hypoxia and T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, integumentary, immune, or skeletal disorders, particularly wound healing and rheumatoid conditions. Similarly, polypeptides and antibodies directed to these poIypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the integumentary system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
skin, connective tissues, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:275 as residues: Thr-42 to Pro-53, Val-78 to Glu-86, Glu-103 to Met-112, Ala-124 to Gly-131.
The tissue distribution in keratinocytes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of integumentary disorders, particularly with regard to wound healing. Furthermore, the tissue distribution also indicates that the translation product of this gene is useful for the treatment and/or detection of disorders of the connective tissues (e.g.
arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, s~leroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:126 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1612 of SEQ ID N0:126, b is an integer of 15 to 1626, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:126, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 117 This gene is expressed primarily in hepatoma and testes tumor, and to a lesser extent, in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hepatic, neural, or reproductive disorders, particularly metastatic liver cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer and metabolic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. liver, brain, reproductive, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, seminal fluid, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in hepatic tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some types of cancer including hepatoma, testes tumor and related metastases.
Furthermore, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g.
hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:127 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between I to 1163 of SEQ ID N0:127, b is an integer of I S
to I 177, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:127, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 118 This gene is expressed primarily in CD34 positive cells, and to a lesser extent, in pancreatic tumor and spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are IS not limited to, reproductive, endocrine, or immune disorders, particularly pancreatic cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumor, immune and metabolic systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, liver, spleen, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, bile, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in pancreatic and CD34 positive cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some types of cancer, especially those involving CD34 cells and pancreatic cancer. Furthermore, expression of this gene product in both CD34 positive cells and spleen indicates a role in the regulation of the proliferation;
survival;
differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, z, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:128 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1262 of SEQ ID N0:128, b is an integer of 15 to 1276, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:128, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 119 This gene is expressed primarily in osteoclastoma, fetal liver/spleen, and to a lesser extent, in primary dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, osteoclastoma; hematopoietic disorders; lymphomas; impaired immunity;
immune disorders; inflammation, in addition to integumentary disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and bone, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, bone, integumentary, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:2?8 as residues: Thr-23 to Pro-29, Thr-68 to Pro-76.
The tissue distribution in dendritic cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of bone and hematopoietic disorders. Elevated levels of expression of this gene product in osteoclastoma indicates that it may play a role in the survival, proliferation, and/or growth of osteoclasts. Therefore, it may be useful in influencing bone mass in such conditions as osteoporosis. More generally, as evidenced by expression in fetal liver/spleen, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the numbers of stem cells and committed progenitors. Expression of this gene product in primary dendritic cells also indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:129 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1320 of SEQ ID N0:129. b is an integer of 15 to 1334, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:129, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 120 When tested against fibroblast cell lines, supernatants removed from cells containing this gene activated the EGR 1 assay. Thus, it is likely that this gene activates fibroblast cells through a signal transduction pathway. Early growth response (EGR1) is a promoter associated with certain genes that induces various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation.
This gene is expressed primarily in hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, soft tissue cancers, such as hemangiopericytoma, in addition to other proliferative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
circulatory system, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:279 as residues: Pro-49 to Thr-64.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of hemangiopericytoma. Furthermore, the biological activity data demonstrates that the translation product of this gene activates fibroblast cells. Fibroblast cells have the abiliy to undergo vascularization, and thus the translation product of this gene may be involved in disorders of the vascular tissue, such as hemangiopericytoma.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:130 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 518 of SEQ ID N0:130, b is an integer of 15 to 532, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:130, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 121 WO 99/22243 PCT/US98l22376 This gene is expressed primarily in kidney cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, renal or urogenital disorders, particularly nephritis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. kidney, cancerous and wounded tissues) or bodily fluids (e.g.iymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:280 as residues: Pro-33 to Ser-38.
The tissue distribution in kidney cortex indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the kidney, including nephritis. Furthermore, the tissue distribution in kidney indicates that this gene or gene product could be used in the treatment and/or detection of kidney diseases including renal failure, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilms Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:131 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 671 of SEQ ID N0:131, b is an integer of 15 to 685, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:131, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 122 This gene is expressed primarily in spleen from chronic iymphocytic leukemia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disordes, such as chronic lymphocytic leukemia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. spleen, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in spleen tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of chronic lymphocytic leukemia. Furthermore, the expression observed predominantly in spleen cells also indicates that the polynucleotides or polypeptides are important in treating and/or detecting hematopoietic disorders, such as graft versus host reaction, graft versus host disease, transplant rejection, myelogenous leukemia, bone marrow fibrosis, and myeloproliferative disease. The polypeptides or polynucleotides are also useful to enhance or protect proliferation, differentiation, and functional activation of hematopoietic progenitor cells (e.g., bone marrow cells), useful in treating cancer patients undergoing chemotherapy or patients undergoing bone marrow transplantation.
The polypeptides or polynucleotides are also useful to increase the proliferation of peripheral blood leukocytes, which can be used in the combat of a range of hematopoietic disorders, including immmunodeficiency diseases, leukemia, and septicemia.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:132 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 715 of SEQ ID N0:132, b is an integer of 15 to 729, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:132, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 123 This gene is expressed primarily in neutrophils, dendritic cells, and CD34 positive cells (Cord Blood).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hematopoietic, or developmental disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, amniotic fluid, plasma. urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of some types of immune disorders, especially those involving neutrophils. More generally, as evidenced by expression in CD34 positive cells, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the numbers of stem cells and committed progenitors. Expression of this gene product in primary dendritic cells also indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:133 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1065 of SEQ ID NO: I33, b is an integer of 15 S to 1079, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:133, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 124 This gene is expressed primarily in adult lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. respiratory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
respiratory, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in lung tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of respiratory disorders, such as asthma, emphysema, and ARDS. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:134 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between i to 1283 of SEQ ID NO: I34, b is an integer of 15 l80 to 1297, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:134, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 125 The gene encoding the disclosed cDNA is thought to reside on chromosome 19.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.
This gene is expressed primarily in T-cell lymphoma and fetal liver/spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, developmental, or hematopoietic disorders, particularly lymphomas. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, developmental, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:284 as residues: Gln-25 to Phe-43.
The tissue distribution in T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of T-cell lymphoma.
Furthermore, expression of this gene product in fetal liver/spleen indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g.
by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma., immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis. In addition, this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:135.and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 603 of SEQ ID N0:135, b is an integer of 15 to 617, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:135, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 126 The translation product of this gene shares sequence homology with C9, a gene of unknown function. The gene encoding the disclosed cDNA is thought to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3. One embodiment of this gene comprises the polypeptides of the following amino acid sequence:
GTAFQHAFSTNDCSRNVYIKKNGFTLHRNPIAQSTDGARTKIGFSEGRHAWEV
WWEGPLGTVA VIGIATKRAPMQCQGYVALLGSDDQSWGWNLVDNNLLHNGE
VNGSFPQCNNAPKYQIGERIRVILDMEDKTLAFERGYEFLGVAFRGLPKVCLYP
AVSAVYGNTEVTLVYLGKPLDG (SEQ ID N0:477). An additional embodiment is the polynucleotides encoding these polypeptides.
This gene is expressed primarily in placenta, and to a lesser extent, in apoptotic T-cells, as well as in smooth muscle, testes, and microvascular endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, reproductive, muscular, vascular, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, amniotic fluid, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in T-cells combined with the homology to the C9 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some immune disorders, especially those involving T-cells.
Furthermore, this gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses), or male infertility.
Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences> such as EST sequences. are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:136 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1297 of SEQ ID N0:136, b is an integer of 15 to 1311, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:136, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 127 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some immune disorders, especially those involving neutrophils. Furthermore, as evidenced by expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in neutrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:137 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1081 of SEQ ID N0:137, b is an integer of 15 to 1095, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:137, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 128 This gene is expressed primarily in neutrophils; IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues ar cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:287 as residues: Lys-36 to Asp-42.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of some immune disorders, especially those involving neutrophils. Furthermore, as evidenced by the expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in neutrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:138 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 678 of SEQ ID N0:138, b is an integer of 1 ~
to 692, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:138, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 129 This gene is expressed primarily in neutrophils, IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, .immune or hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. immune, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:288 as residues: Pro-32 to Gln-38, Gly-51 to Asp-57.
The tissue distribution in neutrophils indicates that poly nucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of certain immune disorders, especially those involving neutrophils. Furthermore, as evidenced by expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in nuetrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for' the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:139 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 734 of SEQ ID N0:139, b is an integer of 15 to 748, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:139, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 130 This gene is expressed primarily in neutrophils, IL-1 and LPS induced.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.
immune, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:289 as residues: Gly-22 to Ser-28.
The tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of certain immune disorders involving neutrophils. Furthermore, as evidenced by expression in neutrophils, this gene may play a role in the survival, proliferation, and/or differentiation of hematopoietic cells in general, and may be of use in augmentation of the number of stem cells and committed progenitors. Expression of this gene product in neutrophils further indicates that it may play a role in mediating responses to infection and controlling immunological responses, such as those that occur during immune surveillance. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:140 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 111$ of SEQ ID N0:140, b is an integer of 15 to 1132, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:140, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 131 This gene is expressed primarily in corpus callosum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural disorders, particularly diseases of the brain, such as neurodegenerative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. brain, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neural tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Brian disorders and diseases, including paranoia, schizophrenia, depression, mania, and Alzheimer's disease. Furthermore, elevated expression of this gene product within the corpus callosum of the brain indicates that it may be involved in neuronal survival;
synapse formation; conductance; neural differentiation, etc. Such involvement may impact many processes, such as learning and cognition. Again. it may also be useful in the treatment of such neurodegenerative disorders as schizophrenia; ALS; or Alzheimer's. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:141 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1098 of SEQ ID N0:141, b is an integer of 15 to 1112, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:141, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 132 The translation product of this gene shares sequence homology with the putative transposase of the Tigger-1 transposon.
This gene is expressed primarily in atrophic endometrium.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, muscular disorders, particularly muscular atrophy. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g. reproductive, muscular, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in endometrial tissue combine with the homology to a transposase indicates that polynucleotides and polypeptides corresponding to this gene are useful for DNA repair in atrophying tissue, particularly of the endornetrium.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:142 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1070 of SEQ ID N0:142, b is an integer of 15 to 1084, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:142, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 133 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: ARAFQHLMVADHSHFHRTLIKQPSMIPNATFYHIF (SEQ ID
N0:478). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in hemangiopericytoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, soft tissue tumors, particularly hemangiopericytoma, or other proliferative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:292 as residues: Ser-39 to Ser-44.
The tissue distribution in hemangiopericytoma indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of various soft-tissue tumors, in addition to other proliferative disorders which may afflict other tissues or cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker andlor immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
t90 ID N0:143 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1036 of SEQ ID N0:143, b is an integer of 15 to 1050, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:143, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: I34 This gene is expressed primarily in hypothalamus of a schizophrenic patient.
and to a lesser extent in spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neural or immune disorders,particularly Schizophrenia or neurodegenerative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the central nervous and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, immune, hematopoietic, spleen, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in hypothalamus indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Schizophrenia, as well as other central nervous system and immune system disorders.
Furthermore, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania.
dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, disorders of the endocrine system, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:144 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1099 of SEQ ID N0:144, b is an integer of 15 to 1113, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:144, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 135 The translation product of this gene shares sequence homology with a chicken ring-finger-zinc finger protein, C-RZF, in addition to, the human multiple membrane spanning receptor TRC8 which is thought to serve as a signaling receptor in renal and thyroid carcinomas. (See Genbank Accession No.gi13395787 (AF064801 )) The TRC8 locus has been described in a family with classical features of hereditary renal cell carcinoma. The 8q24. l (locus of TRCB) breakpoint region encodes the 664-as multiple membrane spanning protein, TRCB, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular Ioop that participates in the binding of sonic hedgehog. In the 3;8 translocation, TRC8 infused to FHIT (fragile histidine triad gene) and is disrupted within the sterol-sensing domain. In contrast, the FHIT coding region is maintained and expressed. In a series of sporadic renal carcinomas, an acquired TRCB mutation was identified. In specific embodiments, polypeptides of the invention comprise the following amino acid sequence:
ARALPEIKGSRLQEINDVCAICYHEFTTSARITPCNHYFHALCLRKWLYIQDTCP
MCHQKVYIEDDIKDN
SNVSNNNGFIPPNETPEEAVREAAAESDRELNEDDSTDCDDDVQRERNGVIQHT
GAAAGRI (SEQ ID N0:479), FSTQAQQLEEFNDDTD (SEQ ID N0:480), RLQE
INDVCAICYHEFTTSARI (SEQ ID N0:48 I ), LYIQDTCPMCHQKVYIEDDI (SEQ
ID N0:482), VSNNNGFIPPNETPEEAVREA (SEQ ID N0:483), and/or DDSTDCD
DDVQRERNGVIQHTGAAAG (SEQ ID N0:484). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 8. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 8.
This gene is expressed primarily in human embryonic tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. developmental abnormalities, particularly congenital defects or proliferative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic tissues, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, renal, endocrine, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in embryonic tissue, combined with the homology to ring finger-zinc finger protein and the human TRC8 receptor indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of abnormalities of the embryonic tissues. in particular proliferative disorders.
In addition, polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, detection, and/or treatment of developmental disorders. The relatively specific expression of this gene product during embryogenesis indicates that it may be a key player in the proliferation, maintenance, and/or differentiation of various cell types during development. It may also act as a morphogen to control cell and tissue type specification. Because of potential roles in proliferation and differentiation, this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. Moreover,this protein may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Thus this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:145 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 671 of SEQ ID N0:145, b is an integer of 15 to 685, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:145, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 136 In specific embodiments, polypeptides of the invention comprise the following amino acid sequence: VAGITGAHHHAQLIFVLLVEMGFHHV GQAGLKLLTSDN
PRTSASQSAGITGMSXGRRITCGQEFKTAVSYNCTTALQPDRAKLCFLFKKKK
KISIQ RTLPGIKRVIYNYERVDSSKGHNSQVQWAHA CNPSTLGGRGGQIV
(SEQ ID N0:485), AGITGAHHHAQLIFVLLVEMGF (SEQ ID N0:486), RVIYN
YERVDSSKGHNSQVQWAHACNP (SEQ ID N0:487). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in microvascular endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular or endothelial disorders, such as the following:
arteriosclerosis, tumorigenesis, stroke, embolism, aneurysm, microvascular disease, and various cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.vascular, endothelial, S cardiovascular, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in microvascular endothelial tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of vascular disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are~related to SEQ
ID N0:146 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1024 of SEQ ID N0:146, b is an integer of 15 to 1038, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:146, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 137 The gene encoding the disclosed cDNA is believed to reside on chromosome 2.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2.
This gene is expressed primarily in fetal tissues, most notably fetal cochlea and fetal lung, and to a lesser extent, in rhabdomyosarcoma and healing groin wound tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include.
but are not limited to, embryological/developmental abnormalities; hearing defects;
respiratory diseases; rhabdomyosarcoma; general cancers and other proliferative conditions;
fibrosis; wound healing. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryo/fetus or of striated muscle cells, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.developmental, pulmonary, auditory, muscle, fibroid, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases involving abnormal cellular proliferation, such as cancer. Expression of this gene product in rapidly proliferating cells, such as those found in the embryo; in rhabdomyosarcomas;
and in wound healing tissue, indicates that this gene may play a role in controlling or promoting cell proliferation. Alternately, expression of this gene in fetal tissues indicates that it may play a role in cellular development and differentiation, particularly of the auditory system as well as the lungs. Thus, this gene product may be useful in the treatment andlor diagnosis of hearing defects, as well as respiratory disorders.
Expression of this gene product in rhabdomyosarcoma indicates that it may play a role in the progression of such cancers, and may also be involved in metastasis and/or angiogenesis. Additionally, expression in wound healing tissues again indicates a role in the proliferation of connective tissue types involved in wound healing, as well as in the fibrosis and scarring that accompanies the wound healing process. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:147 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 837 of SEQ ID N0:147, b is an integer of 15 to 851, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:147, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 138 The gene encoding the disclosed cDNA is believed to reside on chromosome 1.
Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1.
This gene is expressed primarily in adult brain, and to a lesser extent, in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders and diseases of the brain, particularly neurodegenerative and behavior conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:297 as residues: Pro-25 to Ser-30, Thr-36 to Ser-47.
The tissue distribution in neural tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders and diseases of the brain, particularly paranoia, Alzheimer's, depression, schizophrenia, and mania. Moreover, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neopIasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many poIynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences, are related to SEQ
ID N0:148 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly. preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 600 of SEQ ID N0:148, b is an integer of 15 to 614, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:148, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 139 This gene is expressed primarily in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. neural disorders, particularly neurodegenerative disorders, such as Alzheimers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(sl. For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in cerebellum indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of brain diseases and disorders. Specifically, polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as ES'T sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID N0:149 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1186 of SEQ ID N0:149, b is an integer of 15 to 1200, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID N0:149, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: I40 This gene is expressed primarily in brain tissue of a patient with Alzheimer s disease, and to a lesser extent, in human adipose tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. neural or adipose-related disorders, particularly neurodegenerative disorders, such as Alzheimer's disease. Sinularly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.neural, metabolic, adipose, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in neural and adipose tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of Alzheimer's disease and other nervous system disorders.
Moreover, poIynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states, behavioural disorders, or inflamatory conditions such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception. In addition, elevated expression of this gene product in regions of the brain indicates that it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.Moreover, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. More specifically, the protein product of this gene may show utility in the treatment, diagnosis, and/or prevention of neural disorders which occur secondary to aberrations in fatty-acid metabolism, such as improper development of the myelin sheath of nerve cells, for example. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ
ID NO:150 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 669 of SEQ ID NO:150, b is an integer of 15 to 683, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:150, and where b is greater than or equal to a + 14.
FEATURES OF PROTEIN ENCODED BY GENE NO: 141 This Gene is expressed primarily in T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited ta, immune or hematopoietic disorders, particularly T cell leukemia, immunodeficiencies, and inflammatory conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g.immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g.lymph, serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID
N0:300 as residues: Asn-62 to Leu-68.
The tissue distribution T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of T cell leukemia and other disorders of the immune system. Moreover, this gene product may play a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene DE3IIlANDES OU BREVETS VOLUMINEUX
LA PRESENTS PARTIE DE CETTE DEMANDS OU CE BREVET
CECi EST LE TOME ~ DE
NOTE. Pour les tomes additionels, veuillez contacter to Bureau canadien des brevets JUMBO APPLlCATIONS/PATENTS .
THIS SECTION OF THE APPUCATIONIPATENT CONTAINS MORE
'THAN ONE VOLUME
THIS IS VOLUME ~_ OF
' NOTE: For additional volumes-phase contact the Canadian Patent Office .
Claims (23)
1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
(a) a polynucleotide fragment of SEQ ID NO:X or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X;
(b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:Y or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(c) a polynucleotide encoding a polypeptide domain of SEQ ID NO:Y or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(e) a polynucleotide encoding a polypeptide of SEQ ID NO:Y or the cDNA
sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X, having biological activity;
(f) a polynucleotide which is a variant of SEQ ID NO:X;
(g) a polynucleotide which is an allelic variant of SEQ ID NO:X;
(h) a polynucleotide which encodes a species homologue of the SEQ ID NO:Y;
(i) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(h), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues.
(a) a polynucleotide fragment of SEQ ID NO:X or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X;
(b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:Y or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(c) a polynucleotide encoding a polypeptide domain of SEQ ID NO:Y or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(e) a polynucleotide encoding a polypeptide of SEQ ID NO:Y or the cDNA
sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X, having biological activity;
(f) a polynucleotide which is a variant of SEQ ID NO:X;
(g) a polynucleotide which is an allelic variant of SEQ ID NO:X;
(h) a polynucleotide which encodes a species homologue of the SEQ ID NO:Y;
(i) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(h), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues.
2. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a secreted protein.
3. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding the sequence identified as SEQ ID NO:Y or the polypeptide encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X.
4. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises the entire nucleotide sequence of SEQ ID
NO:X or the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X.
NO:X or the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X.
5. The isolated nucleic acid molecule of claim 2, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.
6. The isolated nucleic acid molecule of claim 3, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.
7. A recombinant vector comprising the isolated nucleic acid molecule of claim 1.
8. A method of making a recombinant host cell comprising the isolated nucleic acid molecule of claim 1.
9. A recombinant host cell produced by the method of claim 8.
10. The recombinant host cell of claim 9 comprising vector sequences.
11. An isolated polypeptide comprising an amino acid sequence at least 95%
identical to a sequence selected from the group consisting of:
(a) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(b) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z, having biological activity;
(c} a polypeptide domain of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(d) a polypeptide epitope of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(e) a secreted form of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(f) a full length protein of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(g) a variant of SEQ ID NO: Y;
(h) an allelic variant of SEQ ID NO:Y; or (i) a species homologue of the SEQ ID NO:Y.
identical to a sequence selected from the group consisting of:
(a) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(b) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z, having biological activity;
(c} a polypeptide domain of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(d) a polypeptide epitope of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(e) a secreted form of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(f) a full length protein of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(g) a variant of SEQ ID NO: Y;
(h) an allelic variant of SEQ ID NO:Y; or (i) a species homologue of the SEQ ID NO:Y.
12. The isolated polypeptide of claim 11, wherein the secreted form or the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.
13. An isolated antibody that binds specifically to the isolated polypeptide of claim 11.
14. A recombinant host cell that expresses the isolated polypeptide of claim 11.
15. A method of making an isolated polypeptide comprising:
(a) culturing the recombinant host cell of claim 14 under conditions such that said polypeptide is expressed; and (b) recovering said polypeptide.
(a) culturing the recombinant host cell of claim 14 under conditions such that said polypeptide is expressed; and (b) recovering said polypeptide.
16. The polypeptide produced by claim 15.
17. A method for preventing, treating, or ameliorating a medical condition, comprising administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 11 or the polynucleotide of claim 1.
18. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:
(a) determining the presence or absence of a mutation in the polynucleotide of claim 1; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.
(a) determining the presence or absence of a mutation in the polynucleotide of claim 1; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.
19. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:
(a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.
(a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.
20. A method for identifying a binding partner to the polypeptide of claim 11 comprising:
(a) contacting the polypeptide of claim 11 with a binding partner; and (b) determining whether the binding partner effects an activity of the polypeptide.
(a) contacting the polypeptide of claim 11 with a binding partner; and (b) determining whether the binding partner effects an activity of the polypeptide.
21. The gene corresponding to the cDNA sequence of SEQ ID NO:Y.
22. A method of identifying an activity in a biological assay, wherein the method comprises:
(a) expressing SEQ ID NO:X in a cell;
(b) isolating the supernatant;
(c) detecting an activity in a biological assay; and (d) identifying the protein in the supernatant having the activity.
(a) expressing SEQ ID NO:X in a cell;
(b) isolating the supernatant;
(c) detecting an activity in a biological assay; and (d) identifying the protein in the supernatant having the activity.
23. The product produced by the method of claim 20.
Applications Claiming Priority (35)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6309797P | 1997-10-24 | 1997-10-24 | |
| US6309097P | 1997-10-24 | 1997-10-24 | |
| US6338697P | 1997-10-24 | 1997-10-24 | |
| US6311097P | 1997-10-24 | 1997-10-24 | |
| US6308997P | 1997-10-24 | 1997-10-24 | |
| US6309197P | 1997-10-24 | 1997-10-24 | |
| US6310097P | 1997-10-24 | 1997-10-24 | |
| US6309297P | 1997-10-24 | 1997-10-24 | |
| US6309897P | 1997-10-24 | 1997-10-24 | |
| US6309997P | 1997-10-24 | 1997-10-24 | |
| US6308897P | 1997-10-24 | 1997-10-24 | |
| US6311197P | 1997-10-24 | 1997-10-24 | |
| US6310197P | 1997-10-24 | 1997-10-24 | |
| US6314897P | 1997-10-24 | 1997-10-24 | |
| US6278497P | 1997-10-24 | 1997-10-24 | |
| US6338797P | 1997-10-24 | 1997-10-24 | |
| US6310997P | 1997-10-24 | 1997-10-24 | |
| US60/063,148 | 1997-10-24 | ||
| US60/063,111 | 1997-10-24 | ||
| US60/063,092 | 1997-10-24 | ||
| US60/063,099 | 1997-10-24 | ||
| US60/063,387 | 1997-10-24 | ||
| US60/063,088 | 1997-10-24 | ||
| US60/063,110 | 1997-10-24 | ||
| US60/063,109 | 1997-10-24 | ||
| US60/063,100 | 1997-10-24 | ||
| US60/063,090 | 1997-10-24 | ||
| US60/063,101 | 1997-10-24 | ||
| US60/063,091 | 1997-10-24 | ||
| US60/063,386 | 1997-10-24 | ||
| US60/063,097 | 1997-10-24 | ||
| US60/062,784 | 1997-10-24 | ||
| US60/063,098 | 1997-10-24 | ||
| US60/063,089 | 1997-10-24 | ||
| PCT/US1998/022376 WO1999022243A1 (en) | 1997-10-24 | 1998-10-23 | 148 human secreted proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2307320A1 true CA2307320A1 (en) | 1999-05-06 |
Family
ID=27586006
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002307320A Abandoned CA2307320A1 (en) | 1997-10-24 | 1998-10-23 | 148 human secreted proteins |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1042674A4 (en) |
| JP (1) | JP2003521865A (en) |
| AU (1) | AU1273499A (en) |
| CA (1) | CA2307320A1 (en) |
| WO (1) | WO1999022243A1 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022638A1 (en) * | 2000-09-12 | 2002-03-21 | Human Genome Sciences, Inc. | 22 human secreted proteins |
| US20020137890A1 (en) * | 1997-03-31 | 2002-09-26 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
| CA2363684A1 (en) * | 1999-03-05 | 2000-09-08 | Incyte Pharmaceuticals, Inc. | Human secretory proteins |
| US6331413B1 (en) | 1999-03-17 | 2001-12-18 | Zymogenetics, Inc. | Secreted salivary ZSIG63 Polypeptide |
| CA2374341A1 (en) * | 1999-05-20 | 2000-11-30 | Takeda Chemical Industries, Ltd. | Novel polypeptide |
| FR2796652B1 (en) * | 1999-07-20 | 2003-03-21 | Inst Nat Sante Rech Med | NUCLEIC ACIDS ENCODING PEPTIDES HAVING SORBIN BIOLOGICAL ACTIVITY |
| AU1578801A (en) * | 1999-11-05 | 2001-06-06 | Human Genome Sciences, Inc. | 29 human secreted proteins |
| AU1922301A (en) * | 1999-11-17 | 2001-05-30 | Nyxis Neurotherapies, Inc. | Differential gene expression in cancer |
| EP1280915A1 (en) * | 2000-04-13 | 2003-02-05 | Millennium Pharmaceuticals, Inc. | 23155 novel protein human 5-alpha reductases and uses therefor |
| AU2003294236A1 (en) * | 2002-10-25 | 2004-05-25 | Five Prime Therapeutics, Inc. | Methods of use for novel human polypeptides encoded by polynucleotides |
| TW201100090A (en) * | 2009-04-01 | 2011-01-01 | Oncotherapy Science Inc | C6orf167 peptides and vaccines containing the same |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5597709A (en) * | 1994-01-27 | 1997-01-28 | Human Genome Sciences, Inc. | Human growth hormone splice variants hGHV-2(88) and hGHV-3(53) |
| JPH10510518A (en) * | 1994-12-09 | 1998-10-13 | ヒューマン ジノーム サイエンシーズ,インコーポレイテッド | Human vascular IBP-like growth factor |
| KR19990022283A (en) * | 1995-06-05 | 1999-03-25 | 벤슨 로버트 에이치. | Human Chemokine Beta-11 and Human Chemokine Alpha-1 |
-
1998
- 1998-10-23 AU AU12734/99A patent/AU1273499A/en not_active Abandoned
- 1998-10-23 WO PCT/US1998/022376 patent/WO1999022243A1/en not_active Ceased
- 1998-10-23 JP JP2000518285A patent/JP2003521865A/en not_active Withdrawn
- 1998-10-23 CA CA002307320A patent/CA2307320A1/en not_active Abandoned
- 1998-10-23 EP EP98956146A patent/EP1042674A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999022243A1 (en) | 1999-05-06 |
| AU1273499A (en) | 1999-05-17 |
| EP1042674A4 (en) | 2005-03-23 |
| JP2003521865A (en) | 2003-07-22 |
| EP1042674A1 (en) | 2000-10-11 |
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