Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Xq26-q27 region of the X chromosome is interesting, as an unusually large number of genes and anonymous RFLP probes have been mapped in this area. A number of studies have used classical linkage analysis in families to map this region. Here, we use mutant human T-lymphocyte clones known to be deleted for all or part of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene, to order anonymous probes known to map to Xq26. Fifty-seven T-cell clones were studied, including 44 derived from in vivo mutation and 13 from in vitro irradiated T-lymphocyte cultures. Twenty anonymous probes (DXS10, DXS11, DXS19, DXS37, DXS42, DXS51, DXS53, DXS59, DXS79, DXS86, DXS92, DXS99, DXS100d, DXS102, DXS107, DXS144, DXS172, DXS174, DXS177, and DNF1) were tested for codeletion with the hprt gene by Southern blotting methods. Five of these probes (DXS10, DXS53, DXS79, DXS86 and DXS177) showed codeletion with hprt in some mutants. The mutants established the following unambiguous ordering of the probes relative to the hprt gene: DXS53-DXS79-5'hprt3'-DXS86-DXS10-DXS177 . The centromere appears to map proximal to DXS53. These mappings order several closely linked but previously unordered probes. In addition, these studies indicate that rather large deletions of the functionally haploid X chromosome can occur while still retaining T-cell viability.
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PMID:Fine structure mapping of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene region of the human X chromosome (Xq26). 167 46

Laird has suggested that the mutation responsible for the fragile X (FraX) syndrome interferes with the process of X chromosome reactivation in oocytes, thus blocking the transcription of loci at or neighboring the fragile site (Xq27.3) and producing the clinical FraX phenotype; he has also suggested that the transcriptional block might result from inappropriate DNA methylation. We have explored the latter possibility by examining the methylation status of several genes flanking the fragile site in eight FraX males from seven unrelated families. These genes (HPRT, G6PD, P3, and GdX), contain 5' clusters of CpG dinucleotides which are differentially methylated in transcriptionally active and inactive loci. Using the methylation-sensitive restriction enzyme, HpaII, we observed no differences between FraX and normal males in the methylation either of CpG islands in any of these genes or in nonclustered CpGs within the body of the HPRT gene. The same was true for the CpG cluster in intron 22 of the clotting factor VIII gene. In each gene, the island is methylated on the inactive X chromosome and not on the active one, but in no case were these islands methylated in FraX males. The four anonymous loci (DXS98, DXS304, DXS52, and DXS15) that are closely linked to the FraX locus (the closest is within 5 centimorgans) are not differentially methylated on active and inactive X, nor are they unusually methylated in FraX males. Therefore, our observations provide no evidence that DNA methylation in the vicinity of the FraX locus has a role in producing the clinical phenotype of the FraX syndrome.
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PMID:Methylation status of genes flanking the fragile site in males with the fragile-X syndrome: a test of the imprinting hypothesis. 231 21

The reciprocal t(11;22)(q23;q11) is the most common non-Robertsonian constitutional translocation in humans. The tumor-associated 11;22 rearrangement of Ewing sarcoma (ES) and peripheral neuroepithelioma (NE) is cytologically very similar to the 11;22 constitutional rearrangement. Using immunoglobulin light-chain constant region, ETS1 probes, and the technique of in situ hybridization, we previously were able to show that the constitutional and ES/NE breakpoints are different. As a first step toward isolating these translocation junctions and to further distinguish between them, we have made somatic cell hybrids. Cells from a constitutional 46,XX,inv(9),t(11;22) carrier and from an ES cell line with a t(11;22) were separately fused to a hypoxanthine-guanine phosphoribosyltransferase-deficient Chinese hamster cell line (RJK88). Resulting clones were screened with G-banding and Southern hybridization. Hybrid clones derived from the constitutional t(11;22) were established which contained the der(22) and both the der(22) and the der(11). Hybrid clones derived from the ES cell line containing the der(11) were isolated. Using the technique of Southern hybridization we have sublocalized the loci; ApoA1/C3, CD3D, ETS1, PBGD, THY1, D11S29, D11S34, and D11S147 to the region between the two breakpoints on chromosome 11 and V lambda I, V lambda VI, V lambda VII, and D22S10 to the region between the breakpoints on chromosome 22. Using anonymous DNA probes, we found that D22S9 and D22S24 map proximal to the constitutional breakpoint and that D22S15 and D22S32 map distal to the ES breakpoint on chromosome 22.
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PMID:Comparative mapping of the constitutional and tumor-associated 11;22 translocations. 274 43

We have analyzed the segregation of restriction fragment length polymorphisms (RFLPs) associated with 9 anonymous probes detecting loci DXS10, DXS15, DXS19, DXS37, DXS51, DXS52, DXS98, DXS99, and DXS100 and probes for HPRT and F9 in a set of 40 families segregating fragile X (fra(X]. Using two-point and multipoint analysis, we have established their relative genetic locations. The results indicate that DXS99 and DXS10, unlike previous reports, are not tightly linked to F9. A new locus was found to map within the F9 - fra(X) region. DXS98 showed 6% recombination with fra(X) and appeared to be the closest locus to fra(X). These results will be useful for mapping the relative position of newly defined X probes in this region and for future genetic studies of families with fra(X), hemophilia B, or Lesch-Nyhan mutations.
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PMID:Multipoint linkage of 9 anonymous probes to HPRT, factor 9, and fragile X. 290 96

Using human hypoxanthine-guanine phosphoribosyltransferase (HPRT) cDNA and an anonymous probe 36B-2, we examined the segregation of restriction fragment length polymorphism (RFLP) alleles with the Lesch-Nyhan phenotype in three affected families. Two families were informative. Five carriers of the mutation in one family and two potential carriers in the second were heterozygous for either one or both polymorphisms allowing for prenatal diagnosis. Southern blot patterns in patients from these three families indicated the absence of major structural alterations in the defective gene. Northern analysis using HPRT cDNA as a probe revealed no hybridizing RNA in one patient, whereas normal size mRNA was expressed at a very low level in the second and at a level comparable to normal in the third. These data are consistent with heterogeneity of Lesch-Nyhan genetic lesions resulting from point mutations or small DNA deletions or rearrangements, which may affect transcription, stability, or integrity of the HPRT message.
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PMID:Lesch-Nyhan syndrome: molecular investigation of three French Canadian families using a hypoxanthine-guanine phosphoribosyltransferase cDNA probe. 290 4

Two anonymous X-specific sequences isolated from a genomic library of flowsorted X chromosomal DNA were selected for study because they revealed restriction fragment length polymorphisms in the region Xq26----qter. One sequence, DXS10, detected a two-allele TaqI polymorphic system with allele frequencies of 0.33 and 0.67. The other, 4D-8, defined an MspI polymorphism with allele frequencies of 0.18 and 0.82. DXS10 is tightly linked to the hypoxanthine phosphoribosyltransferase (HPRT) locus with recombination distance theta = O cM at LOD = 5.55 (95% probability limit theta less than 15 cM). DXS10 maps to Xq26 but is not contained within the HPRT locus itself. 4D-8 shows no detectable linkage to the HPRT locus, with maximum likelihood estimate for theta = 50 cM and a LOD score of -2.61 at theta = 5 cM. These two polymorphisms provide additional chromosomal loci for gene mapping by linkage at the distal end of the long arm of the human X chromosome.
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PMID:Two anonymous X-specific human sequences detecting restriction fragment length polymorphisms in region Xq26----qter. 609 63

Characteristics of the allelic polymorphisms of the trimeric AGC repeat of the androgen receptor gene (Xq11-12), exon 1 (AR); the tetrameric ATCT repeat of the von Willebrand factor gene (12p12), intron 40 (vWF); the AGAT repeat of the hypoxanthine phosphoribosyltransferase gene (Xq26) (HPRT); and the AGAT repeat of anonymous DNA sequences of the short arm of chromosome X (STRX1) were studied in 160 DNA samples from unrelated inhabitants of northwestern Russia using the method of polymerase chain reaction. Seventeen, ten, eight, and nine alleles were revealed electrophoretically for short tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The heterozygosity indices for these repeats were 0.80, 0.70, 0.54, and 0.58, respectively. The values for AR and vWF correlated with those expected, according to the Hardy-Weinberg equilibrium, whereas the values for HPRT and STRX1 differed significantly from those theoretically expected. The individualization potentials were 0.045, 0.135, 0.095, and 0.061 for the short tandem repeats of AR, vWF, HPRT, and STRX1, respectively. The distribution of genotypes for the set of these four loci in the population studied was determined. The possibilities of using the studied polymorphic marker systems in molecular diagnosis of the corresponding monogenic diseases--spinal and bulbar muscle atrophy (AR), Lesch-Nyhan disease (HPRT), and von Willebrand disease (vWF)--as well as in population human genetics, testing of personal identity, and molecular approaches to the estimation of mutagenic activity are discussed.
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PMID:[Analysis of the allelic polymorphism of four short tandem repeats in a population from the northwestern region of Russia]. 763 21