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)

X-chromosome inactivation was investigated in human chorionic villi in the first trimester of pregnancy and cultured cells established from them. Expression of glucose-6-phosphate dehydrogenase (G6PD) was evaluated in these extraembryonic cells from four females heterozygous for the electrophoretic variants (AB) of G6PD. In each case the uncultured villi as well as derived cultured cells expressed the AB phenotype for G6PD with about equal intensity for the A and B bands. Single-cell-derived clones established from two of the four cases expressed either G6PD A or B. One clone expressing G6PD B was fused with mouse cells, and a hybrid clone retaining the inactive human X chromosome was isolated; there was no evidence of human G6PD expression in this clone retaining an inactive human X. DNA methylation in the first intron of the human gene for hypoxanthine phosphoribosyltransferase (HPRT) was evaluated in the four pairs of cultured villi and fetal cells. No differences were detected between the cultured villi and fetal cells as they all showed bands characteristic of an inactive X from somatic cells. These results show that there is no preferential inactivation of an X in the majority of cells that constitute human tertiary chorionic villi or in cultured cells derived from them. Long-term cultures established from chorionic villi appear to be no different from somatic cells with respect to X-chromosome inactivation.
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PMID:X-chromosome inactivation in cultured cells from human chorionic villi. 292 38

Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this issue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia--a difference that could prove useful in distinguishing these entities clinically.
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PMID:Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. 334 17

In search of an animal model for the human fragile X syndrome, the chromosomes of Holstein cows were examined. This breed was chosen because of previous studies on the baldy calf syndrome. An achromatic gap was observed at a specific site on the X chromosome closer to the centromere than that identified in humans. This unstained gap was found in 3%-4% of cells of the following four animals: an affected calf, her sister, their mother, and an unrelated Holstein cow. The bovine fragile X may not be analogous to the human fragile X but its location may be important as a genetic marker in linkage studies involving the loci for hypoxanthine phosphoribosyltransferase (HPRT) and glucose-6-phosphate dehydrogenase (G-6-PD).
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PMID:The fragile X in cattle. 345 7

Mammalian sex-dosage compensation is mediated by maintaining activity of only one X chromosome. The asynchronous DNA synthesis characterizing the silent human X chromosome is thought to be reversible only during ontogeny of oocytes. We have previously shown that the glucose-6-phosphate dehydrogenase (G6PD) locus (G6PD) on the allocyclic X chromosome in chorionic villi is partially expressed. We now show that in hybrids derived from a clone of chorionic villi cells (heterozygous for G6PD A) and mouse A9 cells, the loci for G6PD, hypoxanthine phosphoribosyltransferase (HPRT) and phosphoglycerate kinase are expressed on both human X chromosomes; the human X chromosomes carrying either G6PD A or B replicate synchronously with each other and with murine chromosomes. The X chromosome with G6PD A was identified as the original late-replicating X, because methylation in the body of the HPRT gene on this chromosome remained characteristic of the inactive X chromosome. These results indicate that X-chromosome inactivation is completely reversible in cells of trophoblast origin; induction of full transcriptional activity is accompanied by acquisition of isocyclic replication, showing an intimate relationship between these processes. The molecular events responsible for this reversal may be similar to those occurring during maturation of oocytes. Chorionic villi and derivative hybrids provide in vitro models for exploring early events that program the single active X chromosome.
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PMID:Complete reactivation of X chromosomes from human chorionic villi with a switch to early DNA replication. 345 82

In marsupials and eutherian mammals, X chromosome dosage compensation is achieved by inactivating one X chromosome in female cells; however, in marsupials, the inactive X chromosomes is always paternal, and some genes on the chromosome are partially expressed. To define the role of DNA methylation in maintenance of X chromosome inactivity, we examined loci for glucose-6-phosphate dehydrogenase and hypoxanthine phosphoribosyltransferase in a North American marsupial, the opossum Didelphis virginiana, by using genomic hybridization probes cloned from this species. We find that these marsupial genes are like their eutherian counterparts, with respect to sex differences in methylation of nuclease-insensitive (nonregulatory) chromatin. However, with respect to methylation of the nuclease-hypersensitive (regulatory) chromatin of the glucose-6-phosphate dehydrogenase locus, the opossum gene differs from those of eutherians, as the 5' cluster of CpG dinucleotides is hypomethylated in the paternal as well as the maternal gene. Despite hypomethylation of the 5' CpG cluster, the paternal allele, identified by an enzyme variant, is at best partially expressed; therefore, factors other than methylation are responsible for repression. In light of these results, it seems that the role of DNA methylation in eutherian X dosage compensation is to "lock in" the process initiated by such factors. Because of similarities between dosage compensation in marsupials and trophectoderm derivatives of eutherians, we propose that differences in timing of developmental events--rather than differences in the basic mechanisms of X inactivation--account for features of dosage compensation that differ among mammals.
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PMID:DNA methylation stabilizes X chromosome inactivation in eutherians but not in marsupials: evidence for multistep maintenance of mammalian X dosage compensation. 347 42

Monoclonal antibodies that immunoprecipitate human monoamine oxidase (MAO) A or human MAO B, but not the corresponding mouse enzymes, were used to assay for the presence of immunoprecipitable MAO A or MAO B (presumably coded by the respective human genes) in mouse-human hybrid somatic cell lines containing small numbers of human chromosomes. The results were as follow: Extracts of a human lymphoblastoid x mouse hepatoma hybrid line that retained the human X chromosome contained immunoprecipitable MAO B, while a similar hybrid line that contained the same human chromosomes, except for the human X, did not. Extracts of a human fibroblast x mouse neuroblastoma hybrid cell line, whose human chromosomal material consisted solely of the X, contained both immunoprecipitable MAO A and MAO B. Extracts of a related hybrid line, whose human chromosomal material consisted solely of an autonomous fragment and a fragment translocated to a mouse chromosome, contained immunoprecipitable MAO A. However, the level of immunoprecipitable MAO B activity in extracts of this hybrid was low or undetectable. Among extracts of 33 human fibroblast x mouse hepatoma hybrids that had been selected for expression of the X-linked human enzyme HPRT, 60% contained immunoprecipitable MAO B. This figure was comparable to the 58% that expressed the X-linked human isozyme for glucose-6-phosphate dehydrogenase (G6PD). When 11 of these hybrid lines, which contained immunoprecipitable MAO B and human HPRT, were selected for loss of HPRT, all lost immunoprecipitable MAO B in addition to HPRT. These data demonstrate that genes controlling the expression of MAO A and MAO B, which can be immunoprecipitated with the human-specific monoclonal antibodies, are located on the human X chromosome. Properties of the immunological epitopes recognized by the monoclonal antibodies suggest that the X-linked genes detected in this study are probably structural genes for the enzymes.
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PMID:Assignment of genes for human monoamine oxidases A and B to the X chromosome. 354 Mar 17

The inducibility of tyrosine aminotransferase (EC 2.6.1.5) by corticosteroid hormones in rat-human hybrid clones was studied. The presence of human X chromosome activity in the cells was always associated with the suppression of tyrosine aminotransferase inducibility in all the clones examined. Negative correlation between the human X chromosome and inducibility of the enzyme was clearly established. Corticosteroid receptor was present to the same extent in hybrid cell clones that either contained or lost the human X chromosome. The human repressor for inducible tyrosine aminotransferase has a linkage relationship with glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and hypoxanthine-guanine-phosphoribosyltransferase (EC 2.4.2.8) and, therefore, can be assigned to the X chromosome.
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PMID:Human regulatory gene for inducible tyrosine aminotransferase in rat-human hybrids. 414 14

A family is reported in which each of two sisters has a son with no detectable hypoxanthine phosphoribosyltransferase (HPRT) (EC 2. 4. 2. 8) in his erythrocytes, a finding considered pathognomonic of Lesch-Nyhan disease. However, neither has the stigmata of the disease. One boy is neurologically normal, and the other is moderately retarded. There was only a slight increase in urinary uric acid, but the amounts of hypoxanthine and xanthine, and their ratios, were similar to those found in Lesch-Nyhan disease, strongly indicating that excesses of these last two oxypurines are not responsible for the symptomatology in that disease. In contrast to the nondetectable HPRT activity in the red blood cells, leukocyte lysates from the two boys have 10-15% of normal activity, possibly reflecting continuing synthesis of an unstable enzyme. This hypothesis is supported by the demonstration that at 4 degrees C HPRT activity was rapidly lost in the propositus while the activity increased in control subjects. The mother's cells were intermediate between the two. The intact and disrupted leukocytes of the hemizygote, in the absence of added phosphoribosyl converted as much hypoxanthine to inosinate as the normal cell, and appropriate tests indicated that under these circumstances enzyme concentration is not rate limiting whereas the concentration of the cosubstrate, phosphoribosyl pyrophosphate, is. The capacity for normal function in the intact mutant cell is more representative of in vivo conditions than the lysate, which may explain the important modification of clinical symptomatology, the relatively mild hyperuricosuria, and the presence of mosaicism in the circulating blood cells of the heterozygotes. A similar explanation may apply to other genetic diseases in which incomplete but severe enzyme deficiencies are found in clinically normal individuals. An associated deficiency in glucose-6-phosphate dehydrogenase in this family permitted confirmation of previous observations on linkage with hypoxanthine phosphoribosyltransferase.
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PMID:Disparate enzyme activity in erythocytes and leukocytes. A variant of hypoxanthine phosphoribosyl-transferase deficiency with an unstable enzyme. 435 80

Fusion of hypoxanthine phosphoribosyltransferase (HPRT)(-) rat hepatoma cells with HPRT(+) human fibroblasts yielded hybrid clones that grew in HAT selective medium and contained all the rat chromosomes and one to nine human chromosomes. Among the retained chromosomes was the human X chromosome. In all clones backselected in medium containing 8-azaguanine, human X chromosome was absent. Electrophoretic analysis revealed that, without exception, hybrid clones growing in HAT medium had an active HPRT enzyme, either human or rat, or both. When these clones were backselected in 8-azaguanine, they did not show HPRT enzyme activity. Hybrids that contained the human X chromosome also had human glucose-6-phosphate dehydrogenase. The observed reexpression of rat HPRT in hybrid cells derived from HPRT(-) rat cells suggests that a genetic factor from the human cell determined the expression of the rat structural gene for HPRT.
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PMID:Reexpression of the rat hypoxanthine phosphoribosyltransferase gene in rat-human hybrids. 435 57

Somatic cell hybrids have been obtained between SV40-transformed Lesch-Nyhan fibroblasts, which are deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and display glucose-6-phosphate dehydrogenase A (G6PD-A) activity, and late-passage HGPRT-positive W138 human embryo fibroblasts, which display G6PD-B activity. The human-human hybrid clones, which display G6PD-A and G6PD-B and heteropolymers of the two enzyme forms, have the same growth characteristic as the SV40-transformed parental cells and behave as continuous cell lines. The SV40 tumor antigen, the gene for which has been assigned to human chromosome 7, is present in all clones examined.
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PMID:Positive control of transformed phenotype in hybrids between SV40-transformed and normal human cells. 436 42


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