JPH04501357A - Probe for detecting flagyl X syndrome - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Probe for detecting flagyl X syndrome The present invention provides nucleic acid fragments and flagyl Their use in the diagnosis of fragile X syndrome Regarding.

Flagyl X (Martin-Bell) syndrome (McKu sick (catalog number: 30955) has mental retardation, large ears, and oval facial features. It is characterized by physical abnormalities, including macrosomia in male patients (1.2).

When patient-derived lymphocytes are cultured in thymidine-deficient medium, 2-50% of the cells are Expresses fragil site at 27.3 (4.5). 0.6-1/1 for men 000 and 0.2-0.6/1000 for women. Shows that Le X syndrome is the most common genetic cause of mental retardation after Down syndrome. suggest (6.7) However, reliable carrier detection and Early childhood diagnosis shows variable expression of fragil sites in lymphocytes and amniotic fluid cells (8, 9, 10). Genetic counseling also Inheritance of mutations through apparently phenotypically normal males and heterozygous females The situation is difficult due to the variability of expression in (11.12.13).

Although DNA markers associated with flagyl X syndrome have been disclosed, Ranking of markers distal to , difficult because recombination between the marker and the flagyl site occurs more frequently. It was found that (References 14-23). Some studies rank FRAXA- DXS52-F8-Xqter is supported (24.27), other studies are FRA Supports XA-F8-DXS52-Xqter (26.27). relatively recent cross that separates DXS134 from F8 and DXS15. s-over) was found (28), DX between DXS52 and DXS15 Considering the physical map of S134 (29), this data suggests that the rank DXS5 You can get 2-DXS134-DXS 15-F8. closest proximal marker -DX398 (4D8) is connected with a recombination rate of 0.03-0.06 ( 23, 30), while the distal marker DXS52 (St 14) has a recombination rate of 0. ．． 10 (17). The high frequency of single and double crossing phenomena in this region Given this, these loci are not reliable enough for routine clinical use. .

One that avoids the complexity of genetic patterns and the lack of closely linked markers One strategy for identifying the flagyl X locus is that Xq27-q The goal is to create a physical map of the ter. This will determine the marker ranking It should be possible to establish and identify the disease locus. Until now, these genes The locus is physically mapped as a group of three unlinked genes spanning approximately 2 megabases of DNA sequence. has been created (29.31-34).

Thus, the complete physics of this region, estimated to be approximately 12 megabases (32) Target maps require the isolation of new DNA sequences.

This time, the present inventors unexpectedly discovered that although it is distal from the flagyl site, it is located closer to DXS52. discovered a new genetic locus called IAI that exists in close proximity to the human body. This IAI legacy The locus exhibits restriction fragment long-ray type (RFLP), and the IAI locus is closely related. together with the flanking DXS98 provide a useful flanking marker for the flagyl X locus. It was further discovered that Therefore, the IAI locus can be detected The probe is useful for flagyl X syndrome and a number of other X-linked diseases, e.g. Somatic depression, X-linked schizophrenia, X-linked bipolar disease 1llness), Emery Dreifus s) May be useful in the diagnosis of dystrophy and adrenal leukodystrophy (See Reference 15). This locus is similar to F8, DXS52 and color blindness (CB). This is different from previously reported markers for this region (29.3 1-33). Therefore, probes for detecting the IAI locus have additional diagnostic uses. have

Therefore, the present invention provides selective hybridization with the human X chromosome in the region Xq27.3-DXS52. Provides a nucleic acid fragment that can be hybridized.

Fragments of the invention hybridize with the Xq27.3-DXS52 region under low or high stringency conditions. hybridizes with other human chromosomal DNA under these conditions. It would be selective in that sense. Whether this nucleic acid fragment is RNA or DNA, However, the latter is preferred.

More preferably, the fragment is double-stranded DNA. Preferably, the nucleic acid fragment is Let's hybridize at the IAI locus defined below.

When used as probes, the fragments of the invention can be hybridized with human DNA. must be detectable after cation, which can be detected by any known labeling technique. It can be achieved. Typically, probes can be detected by autoradiography. For example, by incorporation of radioactive isotopes by nick translation. It will be marked again. Other labeling methods include directly detectable labels such as fluorescent labels. and the introduction of indirectly detectable labels such as enzyme labels.

Those skilled in the art will be familiar with the incorporation of these and other known labels as well as the detection of such labels. Be familiar with the techniques.

Therefore, the present invention provides a protein comprising the above nucleic acid fragment to which a detectable label is attached. We also provide a web service.

The IAI locus spans at least 2 Mb between the Waladil X site and DXS52. It consists of a region of the X chromosome (but which does not overlap with the DXS52 locus).

Obtained using the restriction enzyme M1uL Notl, NruI or SaclI The digested human X chromosome produced various NA fragments, as described in Example 1 below. ), each fragment hybridizes with the IAI locus. Therefore, lA1 The loci include one or more of the above-mentioned Mlul and NotI.

Nru I and Sac I! X of the human X chromosome where fragments hybridize It is defined as a part of the q27-qter region.

The above MluI, Notl, NruI or SacII fragments are all from this invention. This is an example of a fragment by Akira. Other fragments according to the invention include the IAI gene defined above. and/or one or more of the aforementioned M1uI, NotI, Nru It is a nucleic acid fragment that hybridizes with I or Sac II fragment. known techniques By using Can be used to identify additional fragments that hybridize to the human X chromosome between the Let's come.

Some of this kind of fragments include one or more of the above-mentioned MluI, Notl, Nr Let's hybridize with the ul or SacIr fragment. Warajiru X site and I Other fragments that hybridize with the AI locus are the MluI, N otl.

Although it will not hybridize with any of the NruI or SacII fragments, Nevertheless, they are located closer to the Waladil X site than to the IAI locus. Since the region can be identified, it is useful when searching the human X chromosome for diagnosis of flagyl X disease. It would be useful.

Another fragment of the invention is located on the human X chromosome between the IAI locus and the DXS52 locus. This type of fragment hybridizes with the Mlu1. Note, NruI Or it may or may not hybridize with the Sac II fragment. Not possible. In addition to their use in the diagnosis of flagyl The fragment according to the invention that hybridizes between the It may have further use in diagnosis of linked loci and also the other X stains mentioned above. It may also be used for diagnosing chromosomal diseases. The fragment according to the invention is located between the IAI locus and the DX Hybridizes between S52 diseases.

In the hybridization described here, the fragments to be hybridized are C, O, 1% sodium dodecyl sulfate (SDS), 10% dextran sulfate, and 1x Denhardt solution at 42 °C in buffer containing This is done by washing at 65°C in high or low stringency buffer. SSC is 0 ．． 15M sodium chloride, 0.015M sodium citrate, pH 7.0 buffer solution It is a liquid. Denbardt solution is 0.02% polyvinylpyrrolidone, 0.02% % Ficoll 400, and 0.02% bovine serum albumin (BSA).

The low stringency buffer contains 3xSSC and 0.1% SDS, while the high stringency buffer contains Contains 0.1xSSC and 0.1% SDS. The term “hybrid” used here 'dization', 'low austerity' and 'high austerity' should be interpreted in this way. be.

The fragment according to the invention is a human chromosome X1, preferably Xq27-qte of the X chromosome. Digest the r region, clone the fragments as necessary, and and DXS 52, for example, by selecting fragments that can be hybridized with IAI. It can be obtained by Digestion to produce the fragments defined above, Be aware of the techniques required to perform cloning and screening .

As mentioned above, the nucleic acid fragments of the invention, especially when carrying a detectable label, It can be used to diagnose flagyl X syndrome. Therefore, the present invention potentially treats flagyl X disease. DNA from individuals at risk of contracting the syndrome is converted into nucleic acid fragments or proteins as defined above. flagyl A method for diagnosing the group is also provided. Hybridization of fragments or probes is Can be detected using conventional techniques.

The diagnostic method of the invention preferably involves blood relatives, especially the individual's grandparents, parents, aunts and uncles, siblings and/or Similar screening of DNA samples from children is also included. D.N. The A sample can be obtained fresh or the method can be rie) also applies to stored materials such as those obtained shortly after birth as part of a test. can. This condition in a blood relative combined with a medical history indicating the occurrence of flagyl X syndrome. trace susceptible DNA through the family tree using a unique test and thus identify potential Determine whether individuals at risk have inherited a susceptible X-chromosome bone do. In a particular aspect of the invention, the method of diagnosing patients who are carriers of Flagyl X syndrome. to screen for and/or identify fetuses at risk. It is carried out as a prenatal screening for

Furthermore, the fragments according to the present invention can be similarly used for diagnosing other X-linked diseases mentioned above. Can be used for

The invention further provides a nucleic acid fragment or probe as defined above and one or more The following subcomponents of the above: one or more reagents for labeling nucleic acid fragments; one or more restriction enzymes for digesting the DNA of the hive; one or more for loading digested DNA onto a redization carrier or support. Buffer; hybridization medium for carrying out hybridization. carrier or support such as a filter; for washing hybridization filters; one or more buffers for hybridization - perform hybridization under low or high stringency conditions one or more buffers for detecting the probes defined above; one or more buffers for detecting the probes defined above; reagents; and flagyl X positive and/or negative samples of human DNA and / or control reagents, such as non-human DNA samples, as well as detectable labels. A diagnostic test for flagyl X syndrome containing a reference standard for comparing the signals of We also provide kits to carry out this process.

The XAI locus on the human X chromosome was found to have a highly conserved sequence. This indicates that the lAl locus corresponds to one or more functional genes. are doing. It is likely that the IAI gene or gene group encodes one or more proteins. It is naturally predicted that these proteins would attempt to induce antibodies when used as immunogens. be done. These genes can be isolated and expressed using conventional techniques, and The expressed protein can be used to generate antibodies by known methods.

Proteins, and antibodies to proteins, can themselves be used to diagnose flagyl X syndrome. Wear.

Therefore, in another aspect, the present invention provides a gene corresponding to the lAl locus or one nucleic acid fragment of the present invention as defined above, such as a CDNA corresponding to a gene or more (this expression vector contains Start and stop signals, adjustments and plots in the correct position, direction and reading frame when appropriate. further containing a promoter sequence); Transformed host cells - culturing such transformed host cells containing the expression vector a polypeptide or protein expressed by: such a polypeptide and Polyclonal and monoclonal antibodies against proteins and the differentiation of such antibodies. Antibody-producing cells such as hybridomas capable of secreting antibodies are also provided.

The invention will be explained in more detail by reference to the accompanying drawings: Figure 10 shows DNA position estimation using somatic cell hybrids. DNAt-Ps Digested with tI. The plot shows total I with cold human DNA competitor in A. AI cosmid and, in B, hybridized with subfragment IA1.6. I set it. A: 1. Total human DNA; 2. Human containing Xpter-Xqter /Chinese hamster hybrid; 3, Chinese hamster DNA, 4. Human/mouse hybrid containing Xpter-Xq26; 5. Xq26 -Human/mouse hybrid containing qter: 6, Xp t e r-Xc A human/Chinese hamster hybrid containing en. B:1. Chaini hamster DNA, 2, human male DNA, 3, human female DNA, 4, Xq2 Hybrid B17 containing 7-qter Figure 2. A: PstT erasure in normal individuals IAIRFLP, (Qq, allele of IAI) that appeared after conversion, in the flagyl X family Figure 2 shows the separation of IAI RFLP at .

Figure 3. Nru of human sperm DNA! Digestion is shown (tracks 1 and 2). palusta im and length. IAI and hybridization. Gel is 5C, 100V, 2 It was operated at 00S for 60 hours.

Figure 4. isolated from EBV lymphoblastoid cell lines of different individuals, Notl digested and DNA strips hybridized with IAI (A and C) and F8 (B and D) The plot analysis is shown below. Plots A and B: 1, Flagyl X male; 2, Spastic vs. Paralyzed male patient; 3, flagyl X carrier female; 4, X: female with autosomal translocation 5. Normal male Waradil X carrier. Plots C and D: 1,2, Flagyl X Male; 3.5, normal female; 4, male hemophilia patient; 6, normal male sperm DNA sample Le.

Gels were operated at 50V, 20 minutes, pulse time 5C for 130 hours.

Figure 5. Digested with M1ul (A) and Sac II (B) and hygrogenated with IAI. Southern samples of human DNA isolated from hybridized EBV lymphoblastoid cell lines. Show lot analysis. A: 1.5.6.7.9.1O111゜; 2.1's grandmother's ancestor Mother: 3, normal female. B: l, 2, normal male; 3.4.5, Flagyl X male; 6, Normal female; 7. Male hemophilia patient: 8. Male patient with adrenal myeloneuropathy; 9. Track Grandmother of 10 Flagyl X male's grandmother. Gel at 50V, 20 min pulse time, 1 It was operated for 130 hours at 0C.

The invention is illustrated by reference to the following example. Creation of genetic and physical maps of the new locus IAI located distal to Explain the formation. We found that this locus provides at least a physical map of this region. It is also proven that DNA can be extended by 2 megabases. In the NotI digest, I The pulsed-field gel pattern observed for AI differs from other distal markers. It varies between individuals.

Materials and methods Isolation of Cosmids Human/Chinese Containing the Human X Chromosome as the Only Human Component LTC cosmid library prepared from hamster hybrid DNA constructed into a vector (35). This library was nicked under standard conditions. Screened at low density using slated human genomic DNA, 0.1X Washed using SSC at 65°C. A small amount of positive clones was prepared and digested. Southern plot of Sumid DNA was applied to Chinese hamster and human DNA. Hybridization was performed to confirm the presence of the human X chromosome sequence.

Somatic cell hybrids: hybrids with only the human X chromosome and with the short arm of the X chromosome The containing hybrid has been previously disclosed (36). long arm of human X chromosome Somatic cell hybrids containing various regions were also used. two conflicting mice /Human hybrid is cell line GM3884.46, X, t (X; 16) Derived from (q26; q24). One contains derivative X as the only human chromosome and the other contains derivative 16 as the only human chromosome (37), Xq27- A third hybrid containing qter has t (X:1 9) Micronuclei containing (Xqter-q24:19q13.2-pter) It was induced by irradiation from the hybrid system. This hybrid is F8C, DXS52 and all known Xq28 markers, including DXS 115, but DX3 does not contain any markers proximal to flagyl X such as 98 (38; and van 0ost et al, unpublished).

Southern Blotting Southern blots (39) were performed as previously described. I did (40). Cosmid is Random Briming (41) or Nick Tran Labeled by slation (42), heat denatured, and heat denatured and sonicated The cells were incubated with human DNA (1 mg/ml) for 2 hours. next Dilute the mixture 10x in hybridization buffer containing the appropriate plot. I interpreted it. Filters were washed at 65°C using 0.1x SSC.

Concatenation Program For two-point and multi-point calculations, concatenation program (43.44).

A normal family is the Center D'Etude du Polym in Paris Orphisme Human (C, E, P, H,).

Probes The inventors would like to thank the following people for obtaining probes: 5t14 For (DXS52) (17) and 55E (DXS105) (45) Dr. J-LMandel, Dr. J. Gitschier for R8 (46) Prof. Pearson for 767 (DXS115) (45), and Dr. R9 Nussbaum for 4D8 (47).

Pulsed Field Gel Electrophoresis This is a hexagonal arrangement of electrophoresis as previously described. It was carried out using poles (33°48). Enzymatic quenching of DNA in agarose block The conversion was performed according to the manufacturer's instructions and as detailed in Kenwrick et al. (49). Ru.

IAI isolation and localization Constructed from a somatic hybrid cell line containing the X chromosome as the only human component The resulting library was analyzed in its entirety to select cosmids containing human DNA sequences. Screened at low density using human DNA.

DNA sequence mapping around the flagyl site is derived from a cell line with an X;16 translocation. localization using a somatic cell hybrid panel containing two hybrids of Ta. One hybrid contains the inducible X chromosome and the other contains the inducible chromosome 16 Was. Plot and hybridize labeled cosmids in the presence of total human competitor DNA. soybean (see Methods), but probably had high levels for all cosmids tested. No signal was seen because of the Bell repeat sequence. High well under these conditions One hybridized sequence, IAI, shows its localization to Xq26-qter. (See Figure IA).

The patterns seen on tracks 2 and 5 are not completely identical; This led us to research the possibility of PstIRFLP (see below). (see). Establish whether this sequence is distal or proximal to the flagyl site. A single copy fragment of cosmid IAI containing the Xq27-Xqter Hybridized with DNA from hybrid B17 (see Methods). Figure I From the results in B, this fragment does not produce a clear positive signal in this hybrid DNA. This indicates that the locus D that produces a negative signal in B17 DNA This shows the presence of IAI distal to X398.

Genetic mapping of IAI A single covey PstI fragment was removed from the IAI cosmid and digested with various different restriction enzymes. It was hybridized to DNA from a normal individual that had been digested with. IAl, 1 and One particular fragment named Pstl restriction fragment length in the Caucasian population tested. Polymorphism (RFLP) was shown. allele (5.2 kb band or 2.9 kb band) and two bands at 2.3 kb) are shown in FIG.

35% of the women tested were heterozygous at the IAI position.

We have previously classified using other markers in the Xq26-qter region. Normal DNA from the C, E, P, and H panels was separated using IAI polymorphism. It was similar. The 2-point rod scores are shown in Table 1.

(Margins below this page) Multipoint analysis shows that among the most likely rankings, rank Xcen-DXS10 5-IAI-DXS52-F2O-DXSI 5-Xqter is DXS10 5-DXSI It seems to be twice as large as 15-F2O-DX52-IAI-Xqter. It suggests something. RFLP was only able to obtain information from one family. However, no meaningful data was obtained regarding DXS98.

IAI was also tested against the Flagyl X family.

The 2-point rod scores are shown in Table 1. Data for this family and other family members will be Although it is distal from the radial site, DXS52 has the ability to estimate the position of IAI, which is proximal to the DXS52. (Position score XXXX).

Pulsed field gel electrophoresis experiment Pulsed field gel electrophoresis experiments were carried out using bands in the molecular weight range 800-2000 kb. The procedure was carried out as described in such a way that the two components could be separated. An example of the obtained results is shown in Figure 3. vinegar. IAI is a 1.2 megabase (Mb) protein in the NruI digest of human sperm DNA. Identify the bands (Figure 3).

This IAI fragment is associated with this region such as F8 and DXS52 and color blindness (CB). The markers differ from those previously reported (29.3l-33).

A unique finding regarding IAI is that the bands observed after NotI digestion in different individuals (Figure 4A). This is the same plot hybridized to F8. This is not an artifact of the gel, as it produces the same molecular weight band in all individuals. (Figure 4B). This pattern is also reproducible between gels. Sperm from the same individual and lymphocyte DNA samples yield identical banding patterns (data not shown). Sazu). In genetic analysis, the proximity of IAI to the flagyl site should be considered. Considering this, the present inventors investigated IAI Not in flagyl X-positive men and women. I patterns were also studied (tracks 1.3 and 5 in Figure 4A, track 1 in Figure 4C). and 2). Not only normal individuals but also unrelated flagyl X positive males. Fluctuations are also observed. After N0tl digestion, IAI is approximately 0.85 Mb, 1.2 Detecting all three different bands of Mb and 1.4 Mb. two bands is often seen in both men and women, indicating that this pattern rather than due to variable methylation of restriction enzyme sites. It suggests cheating.

MluI digests of human DNA hybridized to IAI also showed variable This pattern appears in both flagyl X-negative and positive individuals. (Figure 5A). In this experiment, we also determined that the proliferation state of the cells was In order to find out whether or not it changes the growth status, we examined its growth status. Figure 5A minutes from racks 5 and 6 (cells were harvested at early and late log phase, respectively). As shown, the band pattern is the same.

When the 5acII digest of an individual was hybridized to IAI, several bands were observed. show. However, in this case the observed band pattern is (Fig. 5B). (The small apparent variation above is due to loading artifacts. ).

All fragments detected by IAI have previously been mapped in this area. No overlap with what was observed for the loci. For example, IAI, DXS52 and and N0tI fragments for F2O and 1. 2Mb, 1.0Mb and 1 ．． It is 8Mb. Therefore, IAI is a physically separate locus from DXS52. .

None of the PFGE bands were observed with respect to the closest proximal marker DXS98. (Be11 and DaVieS, unpublished observations).

Consideration The present inventors have demonstrated the ability of human Using cell hybrids, we localized the DNA sequence IAI to region Xq27-qter. Established. Therefore, IAI may be used for segregation of flagyl X syndrome. ) would be a useful new marker for analysis. C, E, P, H, family Genetic analysis of IAI revealed that both IAI and DXS52 and F2O (Xq27゜3 (distal marker closest to the flagyl site).

Multi-point analysis of data in these normal families showed that IAI DXS 52 and supports the rank order existing proximal to F2O. lAl and DXS105 ( Xq26/q27 markers such as No tight connections across the dirucite region are observed.

In the flagyl X family, a tight link between IAI and DXS52 is again observed. Ma Multipoint analysis of marker separation indicates that IAI is located proximal to DXS52. This supports the ranking suggested by normal families.

Considering the high frequency of IAI RFLP in the population, IAI is closely related to DXS98 on the proximal side. Together they should be useful flanking markers for the flagyl X locus.

This locus is also associated with Diseases closely associated with DXS52, such as leukodystrophy and adrenal leukodystrophy, It will also be useful for research on other syndromes known to be associated with this disease (see reference 15).

Physical mapping experiments using PFGE show that IAI is located at the previously reported locus. This indicates that a new region of Xq27 that does not overlap is defined (29.3l-3 4). The NotI map derived from the largest fragment detected by the probe used was Summarized below: FRAXA-IJl-DXS52. DxS33. DX! ;15- G6PD, FB, Dxsl15- XqtarWb l-21, 00,30,! , the maximum NotI fragment detected by the dichromatblind probe was 300 kb (32,50), but this locus is relative to the other loci listed above. The ranking is not specified.

IAI thus significantly extends the physical map. Bands larger than IMb The enzymes Not I, NruI, Mlu! and as observed for 5acII Despite the fact that overlapping fragments are found between IA,1 and DXS52. Not possible. The maximum M1uI band identified by IAI is the closest neighbor Colocus DXS52 (approximately 550 kb partial deletion in Mlul digest of human DNA) (detecting compound bands) over 2 Mb that do not overlap (31).

At what height did DXS52 hybridize to the same filter as in Figure 5A? It does not hybridize with any molecular weight band.

PFGE experiments performed by IAI always yield multiband patterns, which suggests that The variable degree of methylation between individuals in this region of q27/28 is shown. these The band pattern is reproducible in each individual's DNA sample. DNA 5 Notably, several bands were obtained in the plot after digestion with acII. Worth noting. In our experience, many 5acII sites are located in non-HTF islands. Consistent with the observation that this enzyme is associated with methylated CpG dinucleotides, almost complete digestion in the vicinity of all other loci in this region tested. (51)

IAI is a large fragment (1 Mb) for several enzymes that have CpG in the recognition site. (or more). Therefore, IAI is F2O, G6PD and DX It exists in a region that is relatively less CpG-rich than S52. Regarding genome structure The biological significance of this observation remains to be elucidated. In recent years, GC-rich areas have It has been shown to be associated with a dyeable G band containing the Aiu sequence (52). , IAI may be present within the dark staining band Xq27. On the other hand, IA I may define regions with different functions within Xq28. this question Further physical mapping will be required to resolve the issue.

Mlu! The size variation observed in the case of and NotI is several hundred kb high. , which is inconsistent with the fragment long-ray type. Relatively small vans in M1uI digest Individuals that produce the same band do not necessarily produce the smallest band in the NotI digest, and vice versa. I can do it. In some Notl-digested male and female DNA samples, the main hive In addition to the lid-forming bands, weaker bands may be visible.

This pattern therefore reflects the different methylation of CpG sites in this region of Xq27/28. This seems to be for the sake of standardization. La1rd (53) observed with Flagyl X syndrome The imprinting theory (imprint ing theory), we recently proposed that methylation is the cause of this imprinting. He suggested that this could be one way to achieve this goal. The experiments described here are In the EBV lineage that does not retain the active X chromosome methylation pattern but does not It was conducted. At present, we have determined that in any case the phenotypic manifestations of Frasil X syndrome and cytogenetic expression of fragil sites at Xq27.3. Suitable for pulsed field gel experiments to investigate whether type and type are related. DNA samples derived from lymphocytes from Flagyl X patients are being collected.

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Claims (15)

[Claims] 1. Selectively hybridizes with the human X chromosome in the region Xq27.3-DXS52 Nucleic acid fragment. 2. 2. A fragment according to claim 1, which is capable of hybridizing under high stringency conditions. 3. The double-stranded DNA fragment according to claim 1 or 2. 4.1A according to any one of claims 1-3, which hybridizes at the A1 locus. piece. 5. A fragment according to any one of claims 1-4 and a detectable label bound thereto. A nucleic acid probe comprising a DNA. 6. The probe according to claim 5, wherein the label is a radioactive label, a fluorescent label or an enzyme label. Bu. 7. Individuals potentially at risk of contracting Flagyl X syndrome or other X-linked diseases The DNA from the body is converted into a nucleic acid fragment or probe according to any one of claims 1 to 5. flagyl Methods for diagnosing group or other X-linked diseases. 8. 8. The method according to claim 7, for diagnosing Flagyl X syndrome. 9. X-linked manic-depressive disorder, X-linked schizophrenia, X-linked bipolar disorder (bip) Emery Dreifu ss) Request for diagnosis of dystrophy or adrenal leukodystrophy The method described in item 7. 10. The nucleic acid fragment or probe according to any one of claims 1 to 6, and one species. or one or more of the following subcomponents: one or more reagents for labeling nucleic acid fragments; a patient; one or more restriction enzymes for digesting the DNA of the hive; one or more for loading digested DNA onto a redization carrier or support. buffer; carrier or support for carrying out hybridization; One or more buffers for washing the diization filter; low or high stringency conditions one or more buffers for carrying out the hybridization under; one or more reagents for detecting probes; human DNA flagyl X positive and One or more control reagents selected from negative samples and non-human DNA samples ; and one or more standards for comparing signals from the detectable label; To conduct diagnostic tests for flagyl X syndrome or other X-linked diseases containing kit. 11. Containing one or more nucleic acid fragments according to any one of claims 1 to 4. a cloning or expression vector, wherein the expression vector is Start and stop signals, regulatory and promoter sequences with location, orientation and reading frame A cloning or expression vector as described above, further comprising: 12. A host transformed with the cloning or expression vector of claim 11. cell. 13. Cultivating host cells transformed with the expression vector according to claim 11. polypeptide or protein obtained by 14. A polyclonal or Monoclonal antibodies. 15. An antibody-producing cell capable of secreting the antibody according to claim 14.