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 transcribed murine A-raf proto-oncogene has been localized to the proximal region of the mouse X chromosome, within the context of four other active genes in this region which together constitute a conserved linkage group between mouse and man. This localization has been accomplished using species-specific restriction fragment length variation and DNAs from a previously defined informative subset of progeny representative of a set of 100 progeny from an interspecific backcross between inbred C57BL/6JRos and wild-derived Mus spretus. This new data regionally orders the mouse A-raf locus relative to the 24 X-linked markers previously examined in this backcross. We find that A-raf co-localizes with two other active genes, tissue inhibitor of metalloproteinases (Timp) and synapsin (Syn-1), 4.0 +/- 2.0 cM distal to the Otc gene at the proximal end of the mouse X chromosome, for a partial gene order in this region of: centromere-Cybb-Otc-Timp/A-raf/Syn-1-Xlr-1-Hprt.
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PMID:Detailed genetic mapping of the A-raf proto-oncogene on the mouse X chromosome. 201 96

Using restriction fragment length polymorphisms (RFLPs) and enzymatic variants between distantly related mouse species, we have assigned three genes to the mouse X chromosome and concurrently mapped a total of eight genes spanning an estimated 50 cM of the chromosome. Segregation of RFLPs in over 200 male progeny from interspecies backcrosses between the inbred strain C57BL/6JRos and either wild-derived Mus musculus or Mus spretus was followed for the murine genes Timp (tissue inhibitor of metalloproteinases), Cf-8 (coagulation factor VIII), and Rsvp (red-sensitive visual pigment) and the known X-linked markers Otc, Hprt, Cf-9, G6pd, and Ags. From the centromere, the gene order was defined as Otc, Timp, Hprt, Cf-9, (Cf-8/Rsvp/G6pd), Ags, by minimizing the number of multiple recombinational events. No significant differences in map order or frequency of recombination were observed between the two backcross series studied. The use of Southern analysis has allowed us to add new genes to the map in a cumulative manner, and as probes become available, additional markers can be mapped, using the same set of mice, by utilizing existing blots or resampling the DNAs. The use of probes for functional genes has allowed us to directly compare the X chromosomes of mouse and man and has provided insight into chromosomal rearrangements which have occurred during the evolutionary divergence of these species, as well as to define the extent of linkage homologies.
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PMID:Multilocus molecular mapping of the mouse X chromosome. 290 27

X inactivation silences most but not all of the genes on one of the two X chromosomes in mammalian females. The human X chromosome preserves its activation status when isolated in rodent/human somatic-cell hybrids, and hybrids retaining either the active or inactive X chromosome have been used to assess the inactivation status of many X-linked genes. Surprisingly, the X-linked gene for human tissue inhibitor of metalloproteinases (TIMP1) is expressed in some but not all inactive X-containing somatic-cell hybrids, suggesting that this gene is either prone to reactivation or variable in its inactivation. Since many genes that escape X inactivation are clustered, we examined the expression of four genes (ARAF1, ELK1, ZNF41, and ZNF157) within approximately 100 kb of TIMP1. All four genes were expressed only from the active X chromosome, demonstrating that the factors allowing TIMP1 expression from the inactive X chromosome are specific to the TIMP1 gene. To determine if this variable inactivation of TIMP1 is a function of the hybrid-cell environment or also is observed in human cells, we developed an allele-specific assay to assess TIMP1 expression in human females. Expression of two alleles was detected in some female cells with previously demonstrated extreme skewing of X inactivation, indicating TIMP1 expression from the inactive chromosome. However, in other cells, no expression of TIMP1 was observed from the inactive X chromosome, suggesting that TIMP1 inactivation is polymorphic in human females.
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PMID:Polymorphic X-chromosome inactivation of the human TIMP1 gene. 1044 76

X-linked progressive retinal atrophy (XLPRA) in the Siberian husky dog is a naturally occurring X-linked retinopathy closely resembling X-linked retinitis pigmentosa (XLRP) in humans. In affected males, initial degeneration of rods is followed by cone degeneration and complete retinal atrophy; carrier females have random patches of rod degeneration consistent with random X chromosome inactivation. By typing the XLPRA pedigree with five intragenic markers [dystrophin, retinitis pigmentosa GTPase regulator ( RPGR ), tissue inhibitor of metalloproteinases 1, androgen receptor and factor IX], we established a linkage map of the canine X chromosome, and confirmed that the order of these five genes is identical to that on the human X. XLPRA was tightly linked to an intragenic RPGR polymorphism (LOD 11.7, zero recombination), thus confirming locus homology with RP3. We cloned the full-length canine RPGR cDNA and three additional splice variants. No disease-causing mutation was found in the RPGR-coding sequence of the four splice variants characterized, a finding similar to approximately 80% of human XLRP patients whose disease maps to the RP3 locus. In addition, there were no significant differences in the proportional expression of each splice variant in normal and pre-degenerate XLPRA-affected retina. Expression of all RPGR splice variants increased later in the disease, when retinas were undergoing active degeneration. The results provide further evidence of cross-species retention of a complex splicing pattern in the 3' portion of RPGR, the functional significance of which is unknown. In addition, the possibility of another disease locus in the RP3 region is supported.
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PMID:Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3). 1069 76

X chromosome inactivation results in dosage equivalency for X-linked gene expression between males and females. However, some X-linked genes show variable X inactivation, being expressed from the inactive X in some females but subject to inactivation in other women. The human tissue inhibitor of metalloproteinases-1 ( TIMP1) gene falls into this category. As TIMP1 and its target metalloproteinases are involved in many biological processes, women with elevated TIMP1 expression may exhibit different disease susceptibilities. To address the potential impact of variable X inactivation, we analyzed TIMP1 expression levels by using an RNase protection assay. The substantial variation of TIMP1 expression observed in cells with monoallelic TIMP1 expression precluded analysis of the contribution of the inactive X to total TIMP1 RNA levels in females, so we examined expression in rodent/human somatic cell hybrids. TIMP1 expression levels varied more widely in hybrids retaining an inactive X than in those with an active X chromosome, suggesting variable retention of the epigenetic silencing mechanisms associated with X inactivation. Therefore, we investigated the contribution of methylation at the promoter to expression level variation and found that methylation of the TIMP1 promoter correlated with instability and low level expression, whereas stable TIMP1expression from the inactive X equivalent to that seen from the active X chromosome was observed when the promoter was unmethylated. Since all female cell lines examined showed methylation of the TIMP1 promoter, the contribution of expression from the inactive X appears minimal. However, as women age, they may accumulate cells stably expressing TIMP1 from the inactive X, with a resulting increase of TIMP1, which may explain some sex differences in various late-onset disorders.
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PMID:Variability of X chromosome inactivation: effect on levels of TIMP1 RNA and role of DNA methylation. 1193 40