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dc.contributor.authorVasudevan, Pradeep
dc.date.accessioned2022-06-16T14:52:49Z
dc.date.available2022-06-16T14:52:49Z
dc.date.issued2021-01
dc.identifier.citationMartin, H. C., Gardner, E. J., Samocha, K. E., Kaplanis, J., Akawi, N., Sifrim, A., Eberhardt, R. Y., Tavares, A., Neville, M., Niemi, M., Gallone, G., McRae, J., Deciphering Developmental Disorders Study, Wright, C. F., FitzPatrick, D. R., Firth, H. V., & Hurles, M. E. (2021). The contribution of X-linked coding variation to severe developmental disorders. Nature communications, 12(1), 627. https://doi.org/10.1038/s41467-020-20852-3en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12904/15610
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.
dc.description.urihttps://www.nature.com/articles/s41467-020-20852-3en_US
dc.language.isoenen_US
dc.subjectdevelopmental disordersen_US
dc.subjectX-linked genesen_US
dc.subjectX-linked genetic disordersen_US
dc.titleThe contribution of X-linked coding variation to severe developmental disordersen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionNAen_US
rioxxterms.versionofrecord10.1038/s41467-020-20852-3en_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.panelUnspecifieden_US
html.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
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


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