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)

A CpG island has been identified just upstream of the first exon of the human monoamine oxidase A (MAOA) gene, localized to Xp11.4-Xp11.23. Southern blotting following digestion with the methylation sensitive restriction endonucleases SmaI, HpaII and HhaI, indicated that CpG dinucleotides within the CpG island were unmethylated on the active X chromosome and extensively methylated on the inactive X chromosome. These sites of differential methylation were close to a polymorphic GT-dinucleotide/VNTR region, which is located 1 kb 3' of the first exon and has a heterozygosity value of 75%. PCR primers were designed for amplification of 1.2-1.3 kb DNA fragments, encompassing both the hypervariable region and a cluster of six HpaII sites within the CpG-rich region. Cleavage of HpaII sites was found to be restricted to active X chromosomes. Therefore, following HpaII digestion, DNA fragments were exclusively amplified from inactive X chromosomes. The resulting PCR products were digested with SacI, which reduced the size of the DNA fragments containing the hypervariable region to 230-330 bp, and were subsequently analyzed on denaturating polyacrylamide gels. Because amplified fragments were exclusively derived from the inactive X chromosome, the relative densities of the two allelic fragments should reflect the proportions of cells that have either of the two X chromosome inactivated. The results of this PCR-based X chromosome inactivation assay were fully concordant with Southern blotting methylation analyses at the PGK locus. It therefore provides a rapid and informative method in tumour clonality analysis and carrier detection in X-linked diseases.
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PMID:An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5' end of the monoamine oxidase A gene. 130 Nov 86

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.
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PMID:Monoamine oxidase deficiency in males with an X chromosome deletion. 248 8

Inherited variations in monoamine oxidase (MAO) activity are thought to affect human behavior and expression of disease. The present study has established the chromosomal location of one of the structural genes coding for this enzyme. Mapping was carried out by somatic cell hybridization between normal human skin fibroblasts and mouse neuroblastoma cells. Selective media for growth of cells with or without hypoxanthine phosphoribosyltransferase (HPRT) activity were used to obtain hybrid lines which had retained or lost the human X chromosome, respectively. Cytogenetic techniques, isozyme analysis, and limited proteolysis and peptide mapping of [3H]pargyline-labeled MAO were used to characterize hybrid lines. With one exception, only lines containing the human X chromosome and human forms of two X-linked enzymes (phosphoglycerate kinase and glucose-6-phosphate dehydrogenase) expressed the human form of the flavin polypeptide of type A MAO. The exceptional hybrid line contained a putative translocation of part of the human X chromosome, since it expressed human forms of both MAO and phosphoglycerate kinase but neither the human form of glucose-6-phosphate dehydrogenase nor HPRT activity. This evidence indicates that the structural gene for the flavin polypeptide of MAO-A is on the human X chromosome. This represents the first chromosomal assignment of a human gene coding for an enzyme of neurotransmitter metabolism. This information will help to elucidate the structure of MAO and modes of its inheritance in the human population.
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PMID:Gene for monoamine oxidase type A assigned to the human X chromosome. 719 39

A nonsense mutation in the X-linked monoamine oxidase A gene has been associated with sex-linked aggressive behaviour.
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PMID:Psychiatric genetics. Misbehaving monoamine oxidase gene. 795 26

We developed an X chromosome inactivation PCR assay, based on differential methylation of the 5' CpG island of the monoamine oxidase A gene (MAOA), close to a highly polymorphic region just downstream of the first exon. The assay provides a method to determine the carrier status of females from pedigrees with X-linked immunodeficiency diseases (XLID).
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PMID:Carrier detection in X-linked immunodeficiencies. I: A PCR-based X chromosome inactivation assay at the MAOA locus. 816 2

Dopamine (DA) availability for precursor function and peripheral biological action is dependent on synthesis and inactivation enzymes, most of them have been cloned and located. An aromatic acid decarboxylase (AADC) defect has been reported in male homozygotic twins. The syndrome of complete dopamine-beta-hydroxylase deficiency with orthostatic hypotension and very high DA contributes to our understanding of the role of DA as a catecholamine with a peripheral biological action of its own. X-linked isolated monoamine oxidase A gene deficiency represents a marked disturbance of monoamine metabolism. The genes of the two major extraneuronal DA-metabolizing enzymes--catechol-O-methyl-transferase and phenolsulfotransferase (PST)-have also been defined. Of particular interest is a bidirectional shuttle system between the PST and sulfatase which have been cloned and located. DA, highly sulfoconjugated via PST, yields DA sulfate which is reconvertible by sulfatase to Free DA. A defect of sulfatase catalyzing this process results in a predominance of DA as biologically inactive DA sulfate and so attenuates the DA action. Enzymatic defects of DA synthesis and metabolism are thus genetic modulators of DA action.
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PMID:Genetic determinants of dopaminergic activity: potential role in blood pressure regulation. 852 34

Modifications have been made to two polymerase chain reaction (PCR) methods for clonality analysis based on the inactivation patterns of two highly polymorphic X-linked genes encoding the androgen receptor (AR) and monoamine oxidase A (MAOA). These methods have been used to examine the clonal nature of frozen tissues from 42 tumours and 25 non-tumour controls from female subjects. Unbalanced inactivation patterns of the genes, which indicate monoclonality, were frequently observed in tumours of heterozygous (informative) cases (18/35 = 51.4 per cent for the AR gene, 9/30 = 30 per cent for the MAOA gene, and 21/38 = 55.2 per cent for both). Among 23 informative non-tumour controls, only one (4.3 per cent), a reactive lymph node, showed skewing in the AR gene. Successful detection of monoclonality was found to depend on the proportion of tumour cells in the tissues examined. None of the AR or MAOA informative cases containing less than 50 per cent of tumour cells showed imbalance in inactivation patterns. With more than 50 per cent of tumour cells in the samples, 66.6 per cent (18/27) of AR and 39.1 per cent (9/23) of MAOA informative cases showed allelic imbalance, with a combined frequency of 72.4 per cent (21/29) of both genes. Our results demonstrate that the methods described are useful for clonal analysis of tissue samples from female patients.
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PMID:Clonality analysis in tumours of women by PCR amplification of X-linked genes. 912 Jul 30

Abnormalities in monoamine oxidase (MAO) levels have been implicated in a wide range of psychiatric disorders. We have examined a VNTR polymorphism at the X-linked MAOA gene to test two hypotheses: (1) Do variants of the MAOA gene play a role in any of the behavioral disorders associated with Tourette syndrome or drug abuse? (2) If so, is there any correlation between the length of the alleles and the phenotypic effect? We examined two independent groups: 375 TS patients, relatives and controls, and 280 substance abusers and controls. The alleles were divided into four groups of increasing size. There was a significant association between the MAOA gene and behavioral phenotypes in both groups, and in both the longest alleles were associated with the greatest phenotypic effect. The strongest effect was for the diagnosis of drug dependence (P=0.00003). The VNTR allele groups were in significant linkage disequilibrium with the Fnu4H1 polymorphism previously shown to be associated with MAO-A activity. While these results are consistent with the possibility that different-sized alleles of the short-repeat polymorphisms themselves may play a role in gene regulation, further studies directly linking these alleles with enzyme levels need to be done.
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PMID:Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse. 949 13

Childhood leukaemia presenting at a young age has been suspected of resulting from a leukaemogenic mutation in parental germ cells, either spontaneously or due to the exposure of a parent to leukaemogenic environmental hazards, particularly ionizing radiation. Mathematical modelling of leukaemogenesis suggests that any such patient would be especially prone to multiple independent leukaemogenic events leading to multiclonality in terms of cell of origin (analogous to bilaterality in familial retinoblastoma). To test this hypothesis we have carried out a search for multiclonal leukaemogenesis in infant and childhood acute lymphoblastic leukaemia (ALL). We used a polymerase chain reaction-based analysis of the X-linked monoamine oxidase A (MAOA) gene locus to study the clonality of marrow samples obtained from female paediatric ALL patients at the time of disease presentation. We obtained presentation samples from 102 patients of whom 72 were found to be informative at the MAOA locus. These included 20 infant leukaemias (< 1 year at diagnosis). Sixty-six samples were found to be unequivocally monoclonal while the remaining six could not, with certainty, be assigned a clonal origin. We also obtained bone marrow aspirates at first relapse as well as at presentation from eight patients. In each case the same pattern of X-linked allelic inactivation was observed at both time points of the course of the disease. No evidence was found for leukaemic multiclonality in any age group at presentation or for leukaemic 'clone-switching' in relapse. These findings suggest that both infant and childhood ALL is of single-cell origin and implies that leukaemic predisposition resulting from germ cell mutation is unlikely to have a major role in their pathogenesis.
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PMID:Clonality analysis suggests that early-onset acute lymphoblastic leukaemia is of single-cell origin and implies no major role for germ cell mutations in parents. 1036 Jun 74

Two X-linked microsatellites, (AC) n repeats at the monoamine oxidase (MAO)-A locus and (TG)n repeats at the MAO-B locus, were studied in 140 unrelated Caucasian male patients with schizophrenia and 91 unrelated Caucasian male controls. Among these subjects, we totally typed out nine alleles for the (AC) n repeats and eight alleles for the (TG) n repeats by using a PCR-based procedure. Allelic frequencies of either (AC) n repeats or (TG) n repeats were not found to be significantly different between patients and controls. However, a significant excess of the (AC)18/(TG)23 haplotype with a relative risk of 4.05 (95%; CI 1.15-14.26) was observed in patients with schizophrenia (Fisher's P = 0.011). The coefficient of linkage disequilibrium (delta) for the (AC)18/(TG)23 haplotype was 0.019 in schizophrenic patients and -0.046 in control subjects, respectively. The latter reached statistical significance (chi 2 = 6.02; df = 1; P < 0.02). The present findings suggest that linkage disequilibrium between polymorphic loci for human MAO-A and MAO-B may be associated with schizophrenia, and the (AC)18/(TG)23 haplotype may render an individual more vulnerable to such an illness.
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PMID:A study of linkage disequilibrium between polymorphic loci for monamine oxidases A and B in schizophrenia. 1069 23


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