Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stability of DNA methylation during aging was assessed in two groups of young (5-20 years old) and old (85-95 years old) women in DNA from blood leukocytes. Three X-linked genes were investigated. Two, G6PD and GdX, are located on Xq28, on the inactivated portion of the X chromosome: demethylation of specific regions of both genes was shown previously to be directly correlated with gene reactivation. The third, MIC2, is located on the pseudoautosomal region of the X chromosome and escapes X inactivation. The 5' region of the G6PD and GdX genes and the body of the G6PD, GDX, and MIC2 genes were analyzed with specific DNA probes. No age-related changes in methylation pattern were detected. We can conclude therefore that the methylation pattern of the three X-linked genes is stable during aging in female leukocytes and that a high rate of age-related reactivation of X-linked genes may not be a feature of all X-linked loci.
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PMID:Stability of DNA methylation of X-chromosome genes during aging. 199 39

To determine the methylation status of female germ cells in reference to the programmed reversal of X chromosome inactivation in these cells, we examined human fetal ovaries at developmental stages from the time germ cells initiate meiosis to when they cease to synthesize DNA (8-21 weeks gestation). Using methylation-sensitive restriction enzymes, we analyzed 57 MspI sites (32 sites in the CpG islands, and 25 nonclustered sites) from five X-linked housekeeping genes (HPRT, G6PD, P3, PGK, and GLA) and two tissue specific genes (X-linked F9 and autosomal EPO). Methylation patterns were compared to those of male germ cells, sperm, and somatic tissues of both sexes. All 32 MspI sites in CpG islands were unmethylated in germ-cell fractions of fetal ovary and adult testes, which could explain the reversibility of X inactivation in these tissues. However, whereas male meiotic germ cells were extensively methylated outside the islands (in the body of genes) and the methylation patterns resembled those of most somatic tissues, none of the 25 nonclustered CpGs was methylated in DNA contributed by the germ-cell component of fetal ovaries. The presence of faint MspI-like fragments in HpaII digests of fetal testes as well as fetal ovary prior to the onset of meiosis suggests that DNA of primordial germ cells is unmethylated in both sexes. Our observations of meiotic germ cells suggest that the female germ cells remain unmethylated, but that methylation in male germ cells occurs postnatally, prior to or during the early stages of spermatogenesis. In any event, the striking sex difference in methylation status of endogenous single-copy genes in meiotic germ cells could provide a molecular basis for parental imprinting of the mammalian genome.
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PMID:Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations. 169 9

The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness and primary asphyxia, has recently been mapped to Xq28. This report presents linkage analysis data of eight families with X-linked centronuclear myopathy. Four probes from the region Xq26-27 and five Xq28 probes were used to get more precise gene localization and marker order. St14 (DXS52), fully informative in all families, shows significant linkage to the CNM gene (z = 3.60; theta = 0.05), followed by DX13 (DXS15) (z = 2.03; theta = 0.06) and F8 (z = 1.86; theta = 0.00). Combination of the physical map derived by Kenwrick and Gitschier (1989) and our linkage data lead to the most probable order R/GCP-G6PD-(XLR-CNM-F8)-p767-St14-cpX67-++ +DX13 placing the CNM gene close to F8. The results of this study confirm strong linkage of the CNM gene to the region Xq28 and will permit carrier testing and prenatal diagnosis in CNM families. We conclude that the precise localization of this devastating disorder may be of great importance for genetic counselling in families at risk. The lack of information about gene frequency and mutation rate as well as the severity and burden of the disease point to the inevitable need for accurate clinical diagnosis.
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PMID:X-linked centronuclear myopathy: mapping the gene to Xq28. 182 1

To determine the overall variation in the G+C% distribution over long ranges of the human genome, DNA sequences of human genes, which were closely linked genetically or physically, were surveyed from the GenBank Data Bank. A total of 72 sequences longer than 2 kb, which were mutually linked within 500 kb, were identified. The sequences belonged to 17 linkage groups and were ordered in each group according to their genetic positions. Analyses of the G+C% distribution along the ordered sequences showed that sequences within each group almost always had similar G+C% levels, but those belonging to different groups often had different levels. Similar analyses of more distantly linked sequences (e.g., greater than 10 Mb) showed mosaic structures of G+C% distribution. These findings are consistent with predictions made from the "isochore" structures found by CsCl equilibrium centrifugation, in that the structures having homogeneous base compositions stretched over at least several hundred kilobases. A possible boundary of the giant G+C% mosaic structures was identified between X-linked G6PD and F8C.
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PMID:Giant G+C% mosaic structures of the human genome found by arrangement of GenBank human DNA sequences according to genetic positions. 224 45

A mouse cDNA probe homologous to the human MCF2 transforming sequence has been identified and partially cloned, and is used here to localize the gene on the mouse X chromosome. The human gene has been physically mapped to within 60 kb of the gene for coagulation factor IX, within a large conserved linkage group between the mouse and human genomes which extends from HPRT to G6PD on the X chromosomes of both mammalian species. In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX. Moreover, segregation of species-specific genomic DNA polymorphisms for Mcf-2 and Cf-9 in a total of 203 individuals derived from two large interspecific mouse backcross populations (which are also segregating for 17 other X-linked molecular markers) demonstrates that the mouse genes are separated by only 0.5 +/- 0.5 cM. Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region. The mouse gene order Hprt-Cf-9-Mcf-2-G6pd predicts a similar ordering of genes on the human X chromosome, a gene order which has only recently been demonstrated by physical mapping. Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome.
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PMID:Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome. 226 64

A 2850-base-pair-long DNA segment containing the transcriptional start site of the human X-linked gene coding for the housekeeping enzyme glucose-6-phosphate dehydrogenase has been fused to the reporter chloramphenicol acetyl transferase gene. This fusion was introduced into three different mammalian cell lines (HepG2, CVI and HeLa). Strong expression was detected and transcription initiated at the natural start site. By deletion analysis, we determined that a 436 base pair region of this promoter is sufficient for full expression of the chimaeric construct and therefore the remainder of the CpC island surrounding the transcriptional start site and differentially methylated in the active and inactive X chromosome is not necessary for transcriptional activity in this assay. Further sequence deletions from -436 to -116 base pairs decrease the promoter-directed chloramphenicol acetyl transferase activity. Site-directed mutagenesis of a TATA-like sequence present in the G6PD promoter shows that this site is required for a correct start of transcription but not for determining the level of gene expression.
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PMID:High levels of transcription driven by a 400 bp segment of the human G6PD promoter. 239 86

We are using pulsed-field gel electrophoresis (PFGE) to establish a physical map of the human Xq28 region. We have identified a new probe 35.239 (DXYS64), localized in Xq28 by somatic hybrid mapping and belonging to a region of greater than 99% homology between the X and the Y chromosomes. PFGE data show that probes 35.239 and the polymorphic locus DXS115 (probe 767) map within a common 300-kb BssHII fragment. Both probes, in addition, hybridize to 575-kb BssHII and 590-kb ClaI fragments that contain the gene coding for coagulation factor VIII (F8C). The order F8C-DXS115-DXYS64 could be determined. Our results also provide evidence for linkage between the red/green color vision locus (RCP,GCP) and probes MD13 and T1.7 (GdX, DXS254) within a 750-kb ClaI fragment. Although the latter two probes are located within 50 kb of the 3' end of the G6PD gene, a G6PD cDNA probe did not hybridize to this fragment. G6PD, on the other hand, could be linked to F8C on a 290-kb BssHII fragment. All these data allow us to propose the order (RCP,GCP)-MD13-GdX-G6PD-F8C-DXS115-DXYS 64. We also linked probes St14 (DXS52), MN12 (DXS33), and DX13 (DXS15) to a member of a small family of X-linked dispersed sequences (DNF22S3) within a 575-kb BssHII fragment. The preliminary physical map presented here should be useful for further fine mapping of disease genes in the Xq28 region and should be helpful in orientating efforts toward the cloning of sequences close to the fragile X syndrome.
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PMID:Toward a physical map of the Xq28 region in man: linking color vision, G6PD, and coagulation factor VIII genes to an X-Y homology region. 250 Dec 12

Structural analysis revealed the existence of two types of subunits in human red cell glucose-6-phosphate dehydrogenase. The two subunits have the same COOH region consisting of 479 amino acid residues, but their NH2-terminal regions are different in size and sequence. The minor subunit can be fully encoded by the X-linked G6PD cDNA, but the NH2-terminal region of the major subunit cannot. The cDNA and the gene for the NH2-terminal region of the major subunit were cloned and characterized. Southern blot hybridization indicated that the gene for the NH2-terminal region is on chromosome 6, not on the X chromosome. Northern blot hybridization demonstrated an existence of two separate mRNA components, one for the COOH-terminal region and the other for the NH2-terminal region. Two separate structural genes, the X-linked and chromosome 6-linked genes, must be coresponsible for encoding the single chain subunit. Either cross-translation of two mRNAs, or transpeptidation, or some other mechanism must be involved in the synthesis of human red cell G6PD.
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PMID:Two structural genes on different chromosomes are required for encoding the major subunit of human red cell glucose-6-phosphate dehydrogenase. 275 68

Fibroblasts cultured from ear pinna biopsies of Virginia opossums (Didelphis virginiana) and red-necked wallabies (Macropus rufogriseus) were examined electrophoretically to determine the relative expression levels of the maternally and paternally derived alleles at X-linked, enzyme-coding loci. Only the maternally derived allele was expressed at the Pgk-A locus in fibroblasts of heterozygous D. virginiana (M. rufogriseus not examined), but fibroblasts of both species exhibited evidence of paternal allele expression at the Gpd locus. Furthermore, the heterozygous G6PD phenotypes in both species were skewed in favor of the maternal gene product, as expected if the paternal allele is only partially (incompletely) expressed. For M. rufogriseus this result is contrary to a previous finding which suggested equal expression of both Gpd alleles in cultured fibroblasts of this species. The present results suggest that X-linked genes in metatherian fibroblasts are subject to the same kind of determinate, paternal allele inactivation, incomplete at some loci, described previously for X-linked genes in adult tissues and that the pattern of paternal X-linked gene expression in these cells is independent of the patterns in the tissues from which the fibroblasts are derived.
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PMID:X-linked gene expression in metatherian fibroblasts: evidence from the Gpd and Pgk-A loci of the Virginia opossum and the red-necked wallaby. 280 26

To explore the extent to which the X chromosome has been conserved during mammalian evolution, we compared six loci that are X-linked in the human genome with the corresponding genes of the North American marsupial, the Virginia opossum (Didelphis virginiana). Our analysis shows that in the opossum genome there are sequences highly homologous to those of human cDNAs for housekeeping genes, glucose-6-phosphoribosyltransferase (HPRT), phosphoglycerate kinase A (PGK1), and alpha-galactosidase A (GLA). However, ornithine transcarbamylase and blood clotting Factor IX--tissue-specific genes that are X-linked in eutherians mammals--have no highly conserved homologs in the marsupial genome. By cloning opossum G6PD and HPRT, we found that these genes are X-linked in the opossum and that homologous sequences are limited to coding regions. As all genomic fragments hybridizing with the human GLA probe show dosage effects, it is likely that the opossum counterpart is X-linked. Finally, the pattern of hybridization suggests that the autosomal pseudogenes of HPRT and PGK1 in the opossum have remained highly homologous to the human X-linked genes.
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PMID:Molecular studies of marsupial X chromosomes reveal limited sequence homology of mammalian X-linked genes. 282 68


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