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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We developed a general method of quantifying relative copy numbers of specific DNA sequences based on the theoretical accumulation of polymerase chain reaction (PCR) products when two DNA sequences are amplified together (co-amplified). Our experiments illustrate the development and theory of the technique. The precision of our estimates is demonstrated by statistical confidence intervals. Tests for effects introduced by experimental factors were performed. The precision of the technique was established by examining the relative gene dosage of the X-linked dystrophin gene in human genomic DNAs from a male, a normal female, a 47,XXX female, and a 48,XXXX cell line. The sensitivity was sufficient to distinguish three copies of the gene from four copies; equivalent to detecting loss of heterozygosity in half the cells of a tumour. Confidence intervals allowed us to reject the hypothesis that there was no difference between DNA samples. Four sample pairs would be required to demonstrate relative gene dosage ratios of 2.0 to 1.0; eight sample pairs would be required to demonstrate a relative gene dosage ratio of 1.3 to 1.0. This method should be useful in detecting gene amplification and deletion in a variety of situations.
Mol Cell Probes 1991 Aug
PMID:Precise gene dosage determination by polymerase chain reaction: theory, methodology, and statistical approach. 179 51

The extent of methylation of DNA sequences upstream and within the two X-linked genes, Pgk-1 and Hprt, was analyzed in male and female somatic cells and in female embryonal carcinoma cells carrying either two active X chromosomes (Xa) or one active and one inactive X chromosome (Xi). Sites upstream and within the first intron of both Pgk-1 and Hprt were heavily methylated on the Xi in somatic cells and in embryonal carcinoma cells with an Xi. Reactivation of this Xi was accompanied by extensive demethylation of these sites. In female embryonal carcinoma cells with two active X chromosomes, one X inactivates during differentiation in culture; however, methylation did not occur during differentiation, consistent with the idea that DNA methylation does not play a role in the initiation of X inactivation but may be involved in maintaining inactivation of those genes on the Xi.
Somat Cell Mol Genet 1991 Jan
PMID:DNA methylation of two X chromosome genes in female somatic and embryonal carcinoma cells. 199 41

Adrenoleukodystrophy (ALD) is a progressive X-linked disorder that produces pathological changes, mainly in the adrenal cortex and the white matter of the central nervous system. The main biochemical abnormality is the accumulation of saturated unbranched fatty acids with a chain length of 24 or more, referred to as very-long-chain fatty acids (VLCFA). Affected children develop large zones of demyelination associated with perivascular lymphoctyic infiltrations resembling those seen in multiple sclerosis. Adults show a more chronic form of the disease, referred to as adrenomyeloneuropathy (AMN). AMN mainly involves the spinal cord ad peripheral nerves, although the cerebral hemispheres may also be affected. Approximately 15% of female carriers have nervous-system involvement that resembles AMN. It is well known that ALD may initially appear as a psychiatric disorder. In the present study, we have assessed the prevalence of cognitive impairment in a group of AMN patients and neurologically symptomatic ALD heterozygotes initially presenting primarily physical complaints. Sixty percent of these patients demonstrated significant neuropsychological impairment, most commonly a pattern of spared and impaired functions typical of a subcortical dementia. We suggest that this progressive cognitive impairment may underlie other behavioral deficits, affirming the significance of the psychological features of this genetically determined disorder.
Mol Chem Neuropathol 1990 Jun
PMID:Cognitive impairment in adult-onset adrenoleukodystrophy. 209 65

All nucleated animal cells synthesize heme to provide the prosthetic group of respiratory cytochromes. Large amounts of heme are synthesized by erythroid cells for hemoglobin production and by liver cells for drug-induced cytochromes P450. This review focuses on the first enzyme of the heme biosynthetic pathway, 5-aminolevulinate synthase (ALAS), which catalyzes the rate-controlling step in liver and possibly other tissues. We report that there are two distinct human genes for ALAS: one, a housekeeping gene, is probably ubiquitously expressed while the other is active only in erythroid tissue. By contrast it has been reported that, for porphobilinogen deaminase, the third enzyme of the heme pathway, there is a single human gene with two promoters; one functional in all tissues, the other erythroid specific. In liver, transcription of the housekeeping ALAS gene is induced by drugs and repressed by heme. Heme also acts in a novel way to prevent transport of ALAS into mitochondria, its site of function. Porphyrias result from inherited defects in enzymes of the heme pathway subsequent to ALAS and the molecular abnormality is now known for the most common subtype of acute intermittent porphyria. In developing red cells, levels of ALAS are regulated by increased gene transcription and by a post-transcriptional mechanism, in which iron most probably controls translation of erythroid ALAS mRNA through an iron-responsive element identified in the 5' untranslated region of the mRNA. The human erythroid ALAS gene is located on the X-chromosome, suggesting that a defect in this gene may be responsible for X-linked sideroblastic anemias.
Mol Biol Med 1990 Oct
PMID:Molecular regulation of 5-aminolevulinate synthase. Diseases related to heme biosynthesis. 209 58

Two gene loci for the E1 alpha subunit of the pyruvate dehydrogenase (PDH) complex have been mapped in the mouse by in situ hybridization. One locus maps to the X chromosome in the region F3-F4, the other to chromosome 19, in band B close to the centromere. This arrangement is exactly comparable to the situation in man where there is an X-linked PDH E1 alpha locus and an autosomal locus on chromosome 4. Comparison of the regional localization of the human and mouse X-linked PDH E1 alpha genes provides further information concerning sites of rearrangement of segments of the X chromosome during mammalian evolution. The human autosomal PDH E1 alpha gene is a "processed" gene, which lacks the introns that are present in the X-linked gene. It codes for a testis-specific E1 alpha subunit that is only expressed after the onset of spermatogenesis. The comparative mapping results in the mouse suggest that the genetic organization and pattern of expression of the two PDH E1 alpha genes is the same in the two species.
Somat Cell Mol Genet 1990 Sep
PMID:Pyruvate dehydrogenase E1 alpha subunit genes in the mouse: mapping and comparison with human homologs. 212 29

Two highly homologous subunits for phosphoribosylpyrophosphate synthetase are encoded by human X-linked genes, PRPS1 and PRPS2 (Taira, M., Kudoh, J., Minoshima, S., Iizasa, T., Shimada, H., Shimizu, Y., Tatibana, M., and Shimizu, N. (1989b) Somat. Cell Mol. Genet. 15, 29-37). These genes are expressed in most tissues, whereas an additional unique mRNA (1.4 kilobases) is present in the testes of rats as well as mice and humans (Taira, M., Iizasa, T., Yamada, K., Shimada, H., and Tatibana, M. (1989a) Biochim. Biophys. Acta 1007, 203-208). In this paper, cDNA cloning revealed that the human testis-specific mRNA was encoded by an autosomal gene, termed PRPS3. RNA blot analysis showed that the expression of this gene began at 4 weeks of age in rats, coinciding with the reported appearance of primary spermatocytes. A cDNA clone of PRPS3 was sequenced and found to encode a predicted product of 317 amino acids which was highly homologous to those of PRPS1 and PRPS2 (94.3% and 91.2% identities, respectively). However, the PRPS3 cDNAs lacked an ATG initiator for translation at the expected position, and instead contained an ACG triplet. In vitro transcription/translation studies, combined with in vitro site-directed mutagenesis experiments, suggested that the ACG codon at this position did serve as a start codon. Analysis of amino-terminal sequence of the radiolabeled PRPS3 product, prepared by in vitro translation, supported the predicted sequence starting with Pro-1, and, in addition, this product was labeled with N-formyl[35S]methionyl-tRNAi. These results suggested that the synthesis of the nascent polypeptide could initiate with methionine at the position corresponding to the ACG codon.
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PMID:A human testis-specific mRNA for phosphoribosylpyrophosphate synthetase that initiates from a non-AUG codon. 216 92

The embryonal carcinoma cell line, C86S1, carries two X chromosomes, one of which replicates late during S phase of the cell cycle and appears to be genetically inactive. C86S1A1 is a mutant which lacks activity of the X-encoded enzyme, hypoxanthine phosphoribosyltransferase (HPRT). Treatment of C86S1A1 cells with DNA-demethylating agents, such as 5-azacytidine (5AC), resulted in (i) the transient expression in almost all cells of elevated levels of HPRT and three other enzymes encoded by X-linked genes and (ii) the stable expression of HPRT in up to 5 to 20% of surviving cells. Most cells which stably expressed HPRT had two X chromosomes which replicated in early S phase. C86S1A1 cells which had lost the inactive X chromosome did not respond to 5AC. These results suggest that DNA demethylation results in the reactivation of genes on the inactive X chromosome and perhaps in the reactivation of the entire X chromosome. No such reactivation occurred in C86S1A1 cells when the cells were differentiated before exposure to 5AC. Thus, the process of X chromosome inactivation may be a sequential one involving, as a first step, methylation of certain DNA sequences and, as a second step, some other mechanism(s) of transcriptional repression.
Mol Cell Biol 1985 Oct
PMID:X chromosome reactivation in mouse embryonal carcinoma cells. 242 74

A clone specific for the rat myelin proteolipid protein (PLP) was isolated from a cDNA library made in pUC18 from 17-day-old rat brain stem mRNA. This clone corresponded to the carboxyl-terminal third of the PLP-coding region. The clone was used to identify PLP-specific mRNAs in mouse brain and to establish the time course of PLP mRNA expression during mouse brain development. Three PLP-specific mRNAs were seen, approximately 1,500, 2,400, and 3,200 bases in length, of which the largest was the most abundant. During brain development, the maximal period of PLP mRNA expression was from 14 to 25 days of age, and this was a similar time course to that for myelin basic protein mRNA expression. When the jimpy mouse, an X-linked dysmyelination mutant, was studied for PLP mRNA expression, low levels of PLP mRNA were seen which were approximately 5% of wild-type levels at 20 days of age. When jimpy brain RNA was analyzed by Northern blotting, the PLP-specific mRNA was shown to be 100 to 200 bases shorter than the wild-type PLP-specific mRNA. This size difference was seen in the two major PLP mRNAs, and it did not result from a loss of polyadenylation of these mRNAs.
Mol Cell Biol 1986 Nov
PMID:Characterization of myelin proteolipid mRNAs in normal and jimpy mice. 243 93

The murine X-linked steroid sulfatase gene (Sts) normally escapes X inactivation. However, we have observed that most long-term murine cell cultures are deficient in STS activity even though only the L cells are known to be derived from an STS- mouse strain. To investigate this phenomenon, we developed a selective system whereby STS+ cells could be selected from STS- populations. The system is based on making cells dependent on cholesterol-sulfate as the sole source of cholesterol, allowing only STS+ cells to grow. Two STS- cell lines, after treatment with either 5-azacytidine (5AC) or ethyl methane sulfonate (EMS), yielded STS+ revertants, suggesting that their STS- phenotype was due to hypermethylation. To study the evolution of STS- cell lines, we established XO and XX primary lines from STS+ strains; the XX cell line remained STS+ after more than 200 cell doublings whereas the XO became STS- after about 100 doublings. Treatment of this STS- XO cell line with 5AC produced clones with restored STS activity. All the revertants showed a growth disadvantage compared to their STS- counterparts. It would appear that aberrant methylation is the basis for much of the STS deficiency observed in established murine lines and that its propagation is due to the growth advantage of STS- over STS+ cells.
Somat Cell Mol Genet 1988 Mar
PMID:Inactivation and reactivation of sex-linked steroid sulfatase gene in murine cell culture. 245 Apr 5

The temperature-sensitive (ts) A1S9 mouse L-cell mutant is defective in an X-linked gene essential for the progression of cells through the S phase of the cell duplication cycle. We recently reported the complementation of the ts A1S9 cell defect with total human DNA and the isolation of independent temperature-resistant transformants that retained a common set of human specific Alu-containing fragments. Here we describe the molecular cloning of these human DNA sequences from one of the secondary transformants. ST-1-0. A genomic library prepared from ST-1-0 was screened with a total human DNA probe, and two recombinant bacteriophages carrying overlapping segments were isolated. The cloned region was extended in both directions using a human X-chromosome specific library. In total, a human region spanning 42 kb in length, and containing all the Alu-specific DNA sequences found in ST-1-0, was isolated in five overlapping recombinant phages. The A1S9 gene appeared to be larger than the DNA recovered in individual phage isolates, as was assessed by transfection experiments. A single-copy probe derived from the phage DNA was shown to be conserved in independent primary, secondary, and tertiary transformants of ts A1S9 cells and mapped to the X chromosome by molecular hybridization. Northern blot hybridization of this probe with poly(A)+ mRNA derived from ST-1-0 cells identified a transcript of about 3.6 kb.
Somat Cell Mol Genet 1989 Nov
PMID:Molecular cloning of human A1S9 locus: an X-linked gene essential for progression through S phase of the cell cycle. 259 54


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