EP0910577A2 - Gene de l'hypertonie - Google Patents

Gene de l'hypertonie

Info

Publication number
EP0910577A2
EP0910577A2 EP97923720A EP97923720A EP0910577A2 EP 0910577 A2 EP0910577 A2 EP 0910577A2 EP 97923720 A EP97923720 A EP 97923720A EP 97923720 A EP97923720 A EP 97923720A EP 0910577 A2 EP0910577 A2 EP 0910577A2
Authority
EP
European Patent Office
Prior art keywords
dsm
gene
hypertension
genome
sequences
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP97923720A
Other languages
German (de)
English (en)
Inventor
Nihat Hacettepe University BILGINTURAN
Sylvia Max-Delbrück-Centrum BÄHRING
Friedrich Max-Delbrück-Centrum LUFT
Herbert Max-Delbrück-Centrum SCHUSTER
Thomas Max-Delbrück-Centrum WIENKER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Progen Biotechnik GmbH
Original Assignee
Progen Biotechnik GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Progen Biotechnik GmbH filed Critical Progen Biotechnik GmbH
Publication of EP0910577A2 publication Critical patent/EP0910577A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • the present invention relates to a gene causing hypertension and its use.
  • Hypertension i.e. Hypertension is one of the most common causes of cardiovascular diseases, especially strokes. Although it has long been known from twin studies that hypertension can be attributed to genetic factors, the ethiological and pathogenetic factors are still largely unknown at present. Molecular methods have advanced the research of hypertension, especially with transgenic animals, but also made it clear that hypertension is a heterogeneous and complex disease which is caused by gene-gene and gene-environment interactions. The search for genes associated with hypertension has so far failed to produce satisfactory results.
  • the present invention is therefore based on the object of providing a means by which the genetic cause of hypertension can be investigated.
  • the present invention thus relates to a gene which is located on chromosome 12p in the genome region between the genome markers AFM338WH5 and D1 2S10-57, in particular between the genome markers D 1 2S1 650 and D12S1 057.
  • the applicant has recognized that the diseases, hypertension, brachydactyly, ie shortening of the limbs, and disruption of the growth of fibroblasts in the form of a shortened cell cycle, are inherited together in an autosomal dominant manner can be. He found that a gene is responsible for this, which is located on chromosome 1 2p in the genome region between the genome markers AFM338WH5 and D 1 2S1057, in particular between the genome markers D1 2S1 650 and D 1 2S1 057. The applicant has obtained this knowledge from studies of a Turkish family, of which 50% of the members suffer from the above diseases. For this purpose, the applicant has carried out an exclusion analysis in which he used conventional genome markers which encompass polymorphic regions of the human genome.
  • the gene according to the invention is located on chromosome 12p in the genome region between the genome markers AFM338WH5 and D12S1 0-57, in particular between the genome markers D 1 2S1 650 and D1 2S1057.
  • the genome markers are available under Database ID: AFM 338WH5, source: J. Weissenbach, Genethon, Database ID: 6DB609807, source: J. Weissenbach, Genethon, or Database ID: GATA-D1 2S1057, source CHLC (Cooperative Human Linkage Center) .
  • the genomic region between the AFM338WH5 and D1 2S1057 genomic markers includes sequences present in the overlapping YAC clones below. These YAC clones are described as follows:
  • the YAC clones were deposited with the DSM (German Collection of Microorganisms and Cell Cultures) under the specified DSM numbers on March 29, 996. Reference is also made to Albertsen et al., PNAS, USA, 87 (1 990), 4256-4260.
  • the preferred genome range between the genome markers D 1 2S1 650 and D1 2S1057 comprises sequences which are present in the above overlapping YAC clones DSM 10624, DSM 10628, DSM 10625, DSM 10629, DSM 10627, DSM 10620, DSM 1061 9 and DSM 1 0621 are present, with particular preference being given to sequences which are present in the YAC clones DSM 1061 9 and DSM 10621, very particularly in the YAC clone DSM 10621.
  • the gene according to the invention can be further characterized. Common tests can be carried out for this. It is beneficial to isolate the genomic DNA from people who suffer from the combination of hypertension and brachydactyly and who have a shortened fibroblast cell cycle. It is particularly favorable if these people come from a family that also includes healthy members. An example of such a family is found in Bilginturan N. et al., J. med. Genet. 10, (1 973), 253-259.
  • the genomic DNA can then be cleaved with the restriction enzyme Sau3AI and the fragments obtained can be used to create a library, e.g. using the bacteriophage P1 as a vector. Positive clones from the library can be confirmed and characterized by further hybridization with other YAC clones (cf. Albrechtsen, supra), which are also in the specified genome range.
  • the positive clones of the library can be used for the transfection of fibroblast cells.
  • fibroblast cells become healthy people, ie those without hypertension and brachydactyly and with a normal cell cycle Fibroblasts, taken. It is favorable if these people come from the same family from which the sick people have been used as donors for the genomic DNA.
  • transfecting the fibroblast cells with the positive clones it can be investigated which of the clones shorten the cell cycle of the fibroblast cells and thus identify themselves as the gene according to the invention. This examination can be carried out using a conventional method (cf. 5- Bromo-2'-deoxy-uridine labeling and Detection Kit III, Cat. No. 1 44461 1, Boehringer Mannheim).
  • the identified clones can be sequenced and their structure clarified. It is thus possible to isolate the gene according to the invention.
  • the gene according to the invention can be cloned, in particular in expression vectors. Examples of such are known to the person skilled in the art.
  • expression vectors for E. coli, these are e.g. pGEMEX, pUC derivatives, pGEX-2T, pET3b and pQE-8.
  • yeast e.g. to call pY100 and Ycpadl
  • animal cells e.g. pKCR, pEFBOS, cDM8 and pCEV4 must be specified.
  • the baculovirus expression vector pAcSGHisNT-A is particularly suitable for expression in insect cells.
  • suitable cells in order to express the gene according to the invention which is present in expression vectors.
  • suitable cells include the E. coli strains HB1 01, DH 1, x1 776, JM 1 01, JM 109, BL21 and SF1 3009, the yeast strain Saccharomyces cerevisiae and the animal cells L, 3T3, FM3A, CHO, COS , Vero and HeLa and the insect cells sf9.
  • the person skilled in the art knows how the gene according to the invention has to be inserted into expression vectors. He is also aware that the gene according to the invention can be inserted in connection with other DNAs coding for further proteins, so that the gene can be expressed in the form of fusion proteins.
  • Such antibodies can be polyclonal or monoclonal. For their production, it is favorable to immunize animals, in particular rabbits or chickens, for polyclonal and mice for monoclonal antibodies with the above protein or fragments thereof. Further “boosters" of the animals can be carried out with the same protein or fragments thereof. Polyclonal antibodies can then be obtained from the serum or egg yolk of the animals. For monoclonal antibodies, animal spleen cells are fused with myeloma cells.
  • nucleic acids in particular DNA and RNA, which are derived from the gene according to the invention and are used to detect the gene according to the invention or mutations thereof.
  • detection can be achieved using conventional DNA and / or RNA determination tests.
  • the results of these tests can be used to make predictions about disease developments or courses, in particular stroke risks.
  • the results can also be the basis for the development of agents that can be used therapeutically for the diseases mentioned.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

L'invention concerne un gène de l'hypertonie situé sur le chromosome 12b dans la région génomique entre les marqueurs génomiques AFM338WH5 et D12S1057, ainsi que l'utilisation de ce gène.
EP97923720A 1996-04-04 1997-04-04 Gene de l'hypertonie Withdrawn EP0910577A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19613606 1996-04-04
DE19613606A DE19613606C1 (de) 1996-04-04 1996-04-04 Gen für Hypertonie
PCT/DE1997/000700 WO1997038082A2 (fr) 1996-04-04 1997-04-04 Gene de l'hypertonie

Publications (1)

Publication Number Publication Date
EP0910577A2 true EP0910577A2 (fr) 1999-04-28

Family

ID=7790535

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97923720A Withdrawn EP0910577A2 (fr) 1996-04-04 1997-04-04 Gene de l'hypertonie

Country Status (5)

Country Link
US (1) US6248873B1 (fr)
EP (1) EP0910577A2 (fr)
JP (1) JP2003518909A (fr)
DE (1) DE19613606C1 (fr)
WO (1) WO1997038082A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10130657A1 (de) * 2001-06-27 2003-01-16 Axaron Bioscience Ag Neues endothetial exprimiertes Protein und seine Verwendung
US9154906B2 (en) 2002-03-28 2015-10-06 Telecommunication Systems, Inc. Area watcher for wireless network

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5374525A (en) * 1992-09-30 1994-12-20 University Of Utah Research Foundation Methods to determine predisposition to hypertension and association of variant angiotensinogen gene and hypertension

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9738082A2 *

Also Published As

Publication number Publication date
US6248873B1 (en) 2001-06-19
JP2003518909A (ja) 2003-06-10
DE19613606C1 (de) 1997-04-30
WO1997038082A3 (fr) 1997-12-11
WO1997038082A2 (fr) 1997-10-16

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