Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A t(X:15)(q23;q25) was detected during cytogenetic investigation of a lymphoblastoid cell line established from a female patient with Fanconi anemia. The translocation was apparently balanced at passage 300 and unbalanced at passage 13. A chromatid exchange between both the normal and the der(15), between the centromere and band 15q25, may explain these results. Replication studies, following BrdU incorporation, indicate that the segment Xq23----qter from the der(15) is early replicating whereas segment Xpter----q23 from the der(X) is late replicating. Since the normal X was early replicating, it is concluded that the segment of the long arm of chromosome X, separated from its inactivation center by the translocation, was reactivated. This interpretation is confirmed by the methylation patterns of the hypoxanthine phosphoribosyltransferase gene (HPRT), mapped on Xq26, which corresponds to that of an active gene, whereas that of phosphoglycerate kinase (PGK1), which remained on the der(X), corresponds to that of an inactive gene. This is the first example of reactivation of a segment of the X chromosome following a structural rearrangement in somatic cells.
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PMID:A t(X;15)(q23;q25) with Xq reactivation in a lymphoblastoid cell line from Fanconi anemia. 185 86

We used the X-linked restriction fragment length polymorphism (RFLP)-methylation strategy to study the clonal basis of the myelodysplastic syndrome (MDS) in seven patients. RFLP-methylation analysis was performed on cell populations from bone marrow (BM) aspirates and peripheral blood using probes specific for the hypoxanthine phosphoribosyltransferase (HPRT) or phosphoglycerate kinase (PGK) gene regions. Density gradient centrifugation methods were used to separate granulocytes and monocytes, and T lymphocytes were positively selected by CD2 (a pan-T marker) immunoconjugated magnetic beads. Cell populations from BM aspirates in 6 of the 7 patients with MDS showed a monoclonal pattern of X-inactivation. The neutrophilic and T-lymphocytic cell fractions were analyzed in 4 of the 6 patients, and the monocytic cell fraction in one of these, and all fractions analyzed showed a similar monoclonal pattern. In 2 of the latter 4 patients, both of whom had normal karyotypes, DNA from a skin biopsy showed a polyclonal pattern. Our data suggest that MDS is a clonal disorder, even in the absence of detectable cytogenetic abnormalities, and that the abnormal clone is capable of myeloid, monocytic, and lymphoid differentiation.
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PMID:Clonal studies in the myelodysplastic syndrome using X-linked restriction fragment length polymorphisms. 197 Apr 87

We determined clonality of thyroid tumors from female patients who had restriction fragment length polymorphisms (RFLP) in the X chromosome genes hypoxanthine phosphoribosyltransferase (HPRT) or phosphoglycerate kinase (PGK). We screened normal thyroid tissue from 59 female patients; of the informative cases 14 were heterozygous for a Bgl I site on PGK and 4 were heterozygous for a Bam HI site on HPRT. In monoclonal tumors, one of the polymorphic alleles was selectively digested after additional digestion with Hpa II, a methylation sensitive enzyme, whereas in polyclonal tissue both were decreased to a similar extent. Normal thyroid tissue from all patients showed a polyclonal pattern. Of the 18 tumors studied, 12 were solitary thyroid nodules, and 6 were obtained from multinodular goiters (MNG). The following were monoclonal: 6/6 follicular adenomas, 2/2 follicular carcinomas, and 1/1 anaplastic carcinoma. Two of the three papillary carcinomas showed intermediate patterns, possibly due to contaminating effects of stromal tissue present in most of these neoplasms. Of the six nodules from MNG, four were polyclonal. The two largest gave a distinct monoclonal pattern. Most solitary thyroid tumors are monoclonal, supporting a somatic cell mutation model of thyroid neoplasm formation. Nodules from MNG are largely hyperplastic, although monoclonal neoplasms do occasionally arise within these glands. The specific somatic mutations leading to clonal expansion and determination of tumor phenotype are presently unknown.
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PMID:Clonal composition of benign and malignant human thyroid tumors. 197 72

We previously reported an X/Y imbalance with a relative excess of X- and a relative deficiency of Y-chromosomal DNA in three out of nine testicular tumors of germ cell origin. To study the implications of those changes the methylation status of DNA from seven of the tumors was explored by HpaII/MspI analysis. The 5' regions of the hypoxanthine phosphoribosyltransferase (HPRT) and the phosphoglycerate kinase (PGK) gene loci exhibited main patterns suggestive of active X chromosomes in the tumors. However, a minority of the HPRT loci of one teratocarcinoma with an increased dosage of the X chromosome, as well as one additional teratocarcinoma, revealed patterns analogous to inactive X chromosomes in females. Using probes from several chromosomes it was subsequently found that the teratocarcinoma tumors (3/3) were characterized by generalized hypermethylation. On the contrary, the seminomas showed variable hypomethylation (4/5) or virtually complete demethylation (1/5). The seminoma with the most extensive hypomethylation was disseminated (stage III), whereas the other seminomas were local (stage I). These findings suggest that DNA methylation may play a role in the developmental pathways leading to different histologic types of testicular tumors of germ cell origin. The HPRT results imply that the consequences of extra X chromosomes--a frequent finding in testicular tumors--may be modulated by mechanisms, such as DNA methylation, that control gene activity.
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PMID:DNA methylation changes in human testicular cancer. 201 91

Three genes on the human inactive X chromosome retained in the Chinese hamster X human hybrid cell line X8/6T2 have been reactivated using the demethylating agent, 5-azacytidine (5-aza-CR). Pulse-labeling and histochemical methods permitted detection and measurement of reactivation rates of the hypoxanthine phosphoribosyltransferase (Hpt) and glucose-6-phosphate dehydrogenase (G6pd) genes within 48 h of treatment. About 50% of the cells became active for these genes, which represents a reactivation rate some 30-fold greater than previously reported in similar systems. The phosphoglycerate kinase (Pgk) gene was not reactivated as frequently as the Hpt or G6pd genes. Segregation analysis of progeny of treated cells showed that enzyme-positive and enzyme-negative cells were produced in proportions supporting the notion that 5-aza-CR causes demethylation by replicative loss and that demethylation leads to reactivation.
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PMID:High-frequency reactivation of X-linked genes in Chinese hamster X human hybrid cells. 244 Jan 16

We analyzed DNA from peripheral-blood and marrow cells from 12 recipients of allogeneic bone marrow transplants to determine whether monoclonal but otherwise normal hematopoiesis occurs in such patients. All patients were being treated for various forms of leukemia or lymphoma. In 10 patients, granulocytes isolated from peripheral-blood samples obtained 28 to 159 days after transplantation were polyclonal. In some, circulating T cells were isolated and also found to be polyclonal. In contrast, two patients had donor-derived monoclonal or oligoclonal hematopoiesis after transplantation. In one, DNA from circulating mononuclear cells obtained 29 days after transplantation revealed a monoclonal pattern on analysis of a restriction-fragment-length polymorphism in the phosphoglycerate kinase gene. In the other, analysis of a restriction-fragment-length polymorphism in the hypoxanthine phosphoribosyltransferase gene suggested the presence of a dominant clone in the granulocytes sampled 36 days after transplantation. When the latter patient was reassessed on day 267, the same clone of donor hematopoietic cells was still predominant and was found to include circulating T cells as well as granulocytes. We conclude that monoclonal hematopoiesis of donor origin may be observed in recipients of allogeneic bone marrow transplants, indicating that stem cells in normal adult human marrow are able to repopulate both lymphoid and myeloid compartments after transplantation.
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PMID:Clonal hematopoiesis demonstrated by X-linked DNA polymorphisms after allogeneic bone marrow transplantation. 262 34

The clonal composition of each cell population was determined from the characteristic methylation pattern of DNA and the restriction fragment length polymorphism (RFLP) of the hypoxanthine phosphoribosyltransferase (HPRT) and phosphoglycerate kinase (PGK) genes, both located on the X chromosome. About 71% of Japanese females are heterozygous in terms of the RFLP of either HPRT or PGK genes, which was demonstrated by using 5' genomic DNA or cDNA probes for these genes. All 3 cases of chronic myeloproliferative disorders showed monoclonal patterns. AML or ALL cases demonstrated either monoclonal or polyclonal patterns depending upon the percentage of blastic cells. Monoclonal patterns were seen in 3 of 4 cases of myelodysplastic syndromes and both PNH cases.
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PMID:Molecular genetic approach to the analysis of clonal proliferation in hematologic disorders. 257 94

We report the identification of a female patient with the X-linked recessive Lesch-Nyhan syndrome (hypoxanthine phosphoribosyltransferase [HPRT] deficiency). Cytogenetic and carrier studies revealed structurally normal chromosomes for this patient and her parents and demonstrated that this mutation arose through a de novo gametic event. Comparison of this patient's DNA with the DNA of her parents revealed that a microdeletion, which occurred within a maternal gamete and involved the entire HPRT gene, was partially responsible for the disease in this patient. Somatic cell hybrids, generated to separate maternal and paternal X chromosomes, showed that expression of two additional X-linked enzymes, phosphoglycerate kinase and glucose-6-phosphate dehydrogenase, were expressed only in cells that contained the maternal X chromosome, suggesting the presence of a functionally inactive paternal X chromosome. Furthermore, comparison of methylation patterns within a region of the HPRT gene known to be important in gene regulation revealed differences between DNA from the father and the patient, in keeping with an active HPRT locus in the father and an inactive HPRT locus in the patient. Together these data indicate that nonrandom inactivation of the cytogenetically normal paternal X chromosome and a microdeletion of the HPRT gene on an active maternal X chromosome were responsible for the absence of HPRT in this patient.
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PMID:Molecular analysis of a female Lesch-Nyhan patient. 276 Feb 9

Part of the higher-order structure of chromatin is achieved by constraining DNA in loops ranging in size from 30 to 100 kilobase pairs; these loops have been implicated in defining functional domains and replicons and possibly in facilitating transcription. Because the human active and inactive X chromosomes differ in transcriptional activity and replication, we looked for differences in their chromatin loop structures. Since the islands of CpG-rich DNA at the 5' ends of X-linked housekeeping genes are the regions where functional differences in DNA methylation and nuclease sensitivity are found, we looked for scaffold association of these sequences after extraction of histones with lithium diiodosalicylate. Specifically, we examined the 5' CpG islands within the hypoxanthine phosphoribosyltransferase, glucose 6-phosphate dehydrogenase, P3, GdX, phosphoglycerate kinase type 1, and alpha-galactosidase loci in human lymphoblasts obtained from individuals with 1 to 4 X chromosomes. Although we detected no scaffold-associated regions near these genes, we found several such regions at the ornithine transcarbamylase and blood clotting factor IX loci. Our results suggest that the CpG islands are excluded from the nuclear scaffold and that even though transcriptionally active, housekeeping genes are less likely than X-linked tissue-specific genes to be scaffold associated. In all cases, the pattern of scaffold association was the same for loci on active and inactive X chromosomes.
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PMID:Chromatin loop structure of the human X chromosome: relevance to X inactivation and CpG clusters. 276 35

Segregation of the X-linked mink markers alpha-galactosidase (GLA), phosphoglycerate kinase-1 (PGK1), hypoxanthine phosphoribosyltransferase (HPRT), and glucose-6-phosphate dehydrogenase (G6PD) was analyzed in hybrids of gamma-irradiated mink fibroblasts and Chinese hamster cells and in hybrids of nonirradiated mink fibroblasts and mouse hepatoma cells. Based on this analysis, the order of the four genes is GLA-PGK1-HPRT-G6PD on the mink X chromosome. Cytogenetic analysis of five mink x Chinese hamster hybrid clones containing mink GLA, PGK1, and HPRT, but lacking G6PD, tentatively localized mink G6PD to Xq15.22----qter and also confirmed the gene order as GLA-PGK1-HPRT-G6PD-qter. Comparison of this order with its counterpart in man and the mouse, as well as an analysis of the G-band patterns of their X chromosomes, demonstrated putative similarities between mink and man and differences in the mouse. These differences may be due to a different rate of X-chromosomal rearrangement in mammalian evolution.
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PMID:Subchromosomal localization and order of GLA, PGK1, HPRT, and G6PD loci on the X chromosome of the American mink (Mustela vison). 284 37


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