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dc.contributor.authorMC LYSAGHT, AOIFE
dc.date.accessioned2013-07-09T09:55:33Z
dc.date.available2013-07-09T09:55:33Z
dc.date.issued2012
dc.date.submitted2012en
dc.identifier.citationPessia E, Makino T, Bailly-Bechet M, McLysaght A, Marais GA, Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome., Proceedings of the National Academy of Sciences of the United States of America, 109, 14, 2012, 5346-5351en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/66655
dc.descriptionPUBLISHEDen
dc.description.abstractHow and why female somatic X-chromosome inactivation (XCI) evolved in mammals remains poorly understood. Ohno proposed a two-step process where XCI is a dosage-compensation mechaQ: 7 nism that evolved to equalize expression levels of X-linked genes in females (2X) and males (1X), with a prior twofold increase in expression of X-linked genes in both sexes [Ohno S (1967) (Springer, Berlin)]. Whereas the parity of X chromosome expression between the sexes has been clearly demonstrated, tests for the doubling of expression levels globally along the X chromosome have returned contradictory results. However, changes in gene dosage during sex-chromosome evolution are not expected to impact on all genes equally, and should have greater consequences for dosage-sensitive genes. We show that, for genes encoding components of large protein complexes (! 7 members)?a class of genes that is expected to be dosage-sensitive?expression of X-linked genes is similar to that of autosomal genes within the complex. These data support Ohno?s hypothesis that XCI acts as a dosage-compensation mechanism, and allow us to re!ne Ohno?s model of XCI evolution. We also explore the contribution of dosage- sensitive genes to X aneuploidy phenotypes in humans, such as Turner (X0) and Klinefelter (XXY) syndromes. X aneuploidy in humans is common and is known to have mild effects because most of the supernumerary X genes are inactivated and not affected by aneuploidy. Only genes escaping XCI experience dosage changes in X-aneuploidy patients. We sensitivity and XCI to compute a list of candidate genes for Xaneuploidy syndromes.en
dc.description.sponsorshipWe thank Xionglei He and Jianzhi Zhang, and Di Nguyen and Christine Disteche for sharing with us the Xiong et al. (15) and Deng et al. (17) datasets, respectively; Judith Ross, Hugues Roest Crollius,Q:17 Erika Kvikstadt, Tristan Lefebure, and Susana Coelho for discussions; and two anonymous referees for their constructive comments. This study was supported by Agence Nationale de la Recherche Grant ANR-08-JCJC-0109 (to G.A.B.M.) and a Science Foundation Ireland grant (to A.M.).en
dc.format.extent5346-5351en
dc.language.isoenen
dc.relation.ispartofseriesProceedings of the National Academy of Sciences of the United States of America;
dc.relation.ispartofseries109;
dc.relation.ispartofseries14;
dc.rightsYen
dc.subjectX-chromosomeen
dc.subject.lcshX-chromosomeen
dc.titleMammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mclysaga
dc.identifier.rssinternalid79679


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