The contribution of X-linked coding variation to severe developmental disorders

DC FieldValueLanguage
dc.contributor.authorMartin, Hilary C.-
dc.contributor.authorGardner, Eugene J.-
dc.contributor.authorSamocha, Kaitlin E.-
dc.contributor.authorGreen, Andrew-
dc.contributor.authoret al.-
dc.date.accessioned2022-08-05T09:22:28Z-
dc.date.available2022-08-05T09:22:28Z-
dc.date.copyright2021 The Authorsen_US
dc.date.issued2021-01-27-
dc.identifier.citationNature Communicationsen_US
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10197/13041-
dc.description.abstractOver 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders.en_US
dc.format.mediumElectronic-
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.subjectX chromosome burden analysisen_US
dc.subjectX-linked disordersen_US
dc.subjectDevelopmental disorder ratesen_US
dc.titleThe contribution of X-linked coding variation to severe developmental disordersen_US
dc.typeJournal Articleen_US
dc.internal.authorcontactotherandrew.green@ucd.ieen_US
dc.statusPeer revieweden_US
dc.identifier.volume12en_US
dc.identifier.startpage1en_US
dc.identifier.endpage13en_US
dc.citation.otherArticle number: 627en_US
dc.identifier.doi10.1038/s41467-020-20852-3-
dc.neeo.contributorMartin|Hilary C.|aut|-
dc.neeo.contributorGardner|Eugene J.|aut|-
dc.neeo.contributorSamocha|Kaitlin E.|aut|-
dc.neeo.contributorGreen|Andrew|aut|-
dc.neeo.contributoret al.||aut|-
dc.description.othersponsorshipUK Research Ethics Committeeen_US
dc.description.othersponsorshipCambridge South Research Ethics Committeeen_US
dc.description.othersponsorshipRepublic of Ireland Research Ethics Committeeen_US
dc.description.othersponsorshipHealth Innovation Challenge Funden_US
dc.description.othersponsorshipWellcome Trust and the UK Department of Healthen_US
dc.description.othersponsorshipWellcome Trust Sanger Instituteen_US
dc.description.othersponsorshipNational Institutes for Health Researchen_US
dc.date.updated2022-08-02T09:05:13Z-
dc.identifier.grantid10/H0305/83-
dc.identifier.grantidGEN/284/12-
dc.identifier.grantidHICF-1009-003-
dc.identifier.grantidWT098051-
dc.rights.licensehttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/en_US
item.fulltextWith Fulltext-
item.grantfulltextopen-
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