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Article: CNV analysis in Chinese children of mental retardation highlights a sex differentiation in parental contribution to de novo and inherited mutational burdens

TitleCNV analysis in Chinese children of mental retardation highlights a sex differentiation in parental contribution to de novo and inherited mutational burdens
Authors
Issue Date2016
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2016, v. 6, p. article no. 25954 How to Cite?
AbstractRare copy number variations (CNVs) are a known genetic etiology in neurodevelopmental disorders (NDD). Comprehensive CNV analysis was performed in 287 Chinese children with mental retardation and/or development delay (MR/DD) and their unaffected parents. When compared with 5,866 ancestry-matched controls, 11~12% more MR/DD children carried rare and large CNVs. The increased CNV burden in MR/DD was predominantly due to de novo CNVs, the majority of which (62%) arose in the paternal germline. We observed a 2~3 fold increase of large CNV burden in the mothers of affected children. By implementing an evidence-based review approach, pathogenic structural variants were identified in 14.3% patients and 2.4% parents, respectively. Pathogenic CNVs in parents were all carried by mothers. The maternal transmission bias of deleterious CNVs was further replicated in a published dataset. Our study confirms the pathogenic role of rare CNVs in MR/DD, and provides additional evidence to evaluate the dosage sensitivity of some candidate genes. It also supports a population model of MR/DD that spontaneous mutations in males’ germline are major contributor to the de novo mutational burden in offspring, with higher penetrance in male than female; unaffected carriers of causative mutations, mostly females, then contribute to the inherited mutational burden.
Persistent Identifierhttp://hdl.handle.net/10722/231246
ISSN
2015 Impact Factor: 5.228
2015 SCImago Journal Rankings: 2.073

 

DC FieldValueLanguage
dc.contributor.authorWang, B-
dc.contributor.authorJi, T-
dc.contributor.authorZhou, X-
dc.contributor.authorWang, J-
dc.contributor.authorWang, X-
dc.contributor.authorWang, JM-
dc.contributor.authorZhu, D-
dc.contributor.authorZhang, XJ-
dc.contributor.authorSham, PC-
dc.contributor.authorZhang, XG-
dc.contributor.authorMa, X-
dc.contributor.authorJiang, Y-
dc.date.accessioned2016-09-20T05:21:46Z-
dc.date.available2016-09-20T05:21:46Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, p. article no. 25954-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/231246-
dc.description.abstractRare copy number variations (CNVs) are a known genetic etiology in neurodevelopmental disorders (NDD). Comprehensive CNV analysis was performed in 287 Chinese children with mental retardation and/or development delay (MR/DD) and their unaffected parents. When compared with 5,866 ancestry-matched controls, 11~12% more MR/DD children carried rare and large CNVs. The increased CNV burden in MR/DD was predominantly due to de novo CNVs, the majority of which (62%) arose in the paternal germline. We observed a 2~3 fold increase of large CNV burden in the mothers of affected children. By implementing an evidence-based review approach, pathogenic structural variants were identified in 14.3% patients and 2.4% parents, respectively. Pathogenic CNVs in parents were all carried by mothers. The maternal transmission bias of deleterious CNVs was further replicated in a published dataset. Our study confirms the pathogenic role of rare CNVs in MR/DD, and provides additional evidence to evaluate the dosage sensitivity of some candidate genes. It also supports a population model of MR/DD that spontaneous mutations in males’ germline are major contributor to the de novo mutational burden in offspring, with higher penetrance in male than female; unaffected carriers of causative mutations, mostly females, then contribute to the inherited mutational burden.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleCNV analysis in Chinese children of mental retardation highlights a sex differentiation in parental contribution to de novo and inherited mutational burdens-
dc.typeArticle-
dc.identifier.emailZhou, X: zhouxy@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.authoritySham, PC=rp00459-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep25954-
dc.identifier.hkuros266405-
dc.identifier.volume6-
dc.identifier.spagearticle no. 25954-
dc.identifier.epagearticle no. 25954-
dc.publisher.placeUnited Kingdom-

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