De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

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dc.citation.epage23en_US
dc.citation.issueNumber1en_US
dc.citation.spage16en_US
dc.citation.volumeNumber9en_US
dc.contributor.authorDong, S.en_US
dc.contributor.authorWalker, M.F.en_US
dc.contributor.authorCarriero, N.J.en_US
dc.contributor.authorDiCola, M.en_US
dc.contributor.authorWillsey, A.en_US
dc.contributor.authorYe, A.Y.en_US
dc.contributor.authorWaqar, Z.en_US
dc.contributor.authorGonzalez L.E.en_US
dc.contributor.authorOverton J.D.en_US
dc.contributor.authorFrahm, S.en_US
dc.contributor.authorKeaney J.F.en_US
dc.contributor.authorIII, Teran, N.A.en_US
dc.contributor.authorDea J.en_US
dc.contributor.authorMandell J.D.en_US
dc.contributor.authorHusBal V.en_US
dc.contributor.authorSullivan, C.A.en_US
dc.contributor.authorDiLullo, N.M.en_US
dc.contributor.authorKhalil, R.O.en_US
dc.contributor.authorGockley J.en_US
dc.contributor.authorYuksel, Z.en_US
dc.contributor.authorSertel, S.M.en_US
dc.contributor.authorErcan-Sencicek, A.G.en_US
dc.contributor.authorGupta, A.R.en_US
dc.contributor.authorMane, S.M.en_US
dc.contributor.authorSheldon, M.en_US
dc.contributor.authorBrooks, A.I.en_US
dc.contributor.authorRoeder, K.en_US
dc.contributor.authorDevlin, B.en_US
dc.contributor.authorState, M.W.en_US
dc.contributor.authorWei L.en_US
dc.contributor.authorSanders, S.J.en_US
dc.date.accessioned2016-02-08T11:00:35Z
dc.date.available2016-02-08T11:00:35Z
dc.date.issued2014en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractWhole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR= 1.6; 95% CI= 1.0-2.7; p= 0.03), are more common in female probands (p= 0.02), are enriched among genes encoding FMRP targets (p= 6× 10-9), and arise predominantly on the paternal chromosome (p< 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. © 2014 The Authors.en_US
dc.description.provenanceMade available in DSpace on 2016-02-08T11:00:35Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 70227 bytes, checksum: 26e812c6f5156f83f0e77b261a471b5a (MD5) Previous issue date: 2014en
dc.identifier.doi10.1016/j.celrep.2014.08.068en_US
dc.identifier.issn22111247
dc.identifier.urihttp://hdl.handle.net/11693/26490
dc.language.isoEnglishen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.celrep.2014.08.068en_US
dc.source.titleCell Reportsen_US
dc.subjectcell proteinen_US
dc.subjectfragile X mental retardation proteinen_US
dc.subjectmixed lineage leukemia proteinen_US
dc.subjectmixed lineage leukemia protein 5en_US
dc.subjectregulating synaptic exocytosis 1en_US
dc.subjectunclassified drugen_US
dc.subjectanimal cellen_US
dc.subjectanimal tissueen_US
dc.subjectArticleen_US
dc.subjectautismen_US
dc.subjectCHD2 geneen_US
dc.subjectchromatin structureen_US
dc.subjectcontrolled studyen_US
dc.subjectexomeen_US
dc.subjectfemaleen_US
dc.subjectframeshift mutationen_US
dc.subjectgeneen_US
dc.subjectgene deletionen_US
dc.subjectgene insertionen_US
dc.subjectgene sequenceen_US
dc.subjectgenetic associationen_US
dc.subjectgenetic identificationen_US
dc.subjectgenetic risken_US
dc.subjectgenetic variabilityen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjecthuman tissueen_US
dc.subjectindel mutationen_US
dc.subjectintellectual impairmenten_US
dc.subjectKMT2E geneen_US
dc.subjectmajor clinical studyen_US
dc.subjectmaleen_US
dc.subjectmissense mutationen_US
dc.subjectmouseen_US
dc.subjectnonhumanen_US
dc.subjectopen reading frameen_US
dc.subjectparental ageen_US
dc.subjectpaternalismen_US
dc.subjectPHF3 geneen_US
dc.subjectprotein protein interactionen_US
dc.subjectRIMS1 geneen_US
dc.subjectsequence alignmenten_US
dc.subjectsex differenceen_US
dc.subjectsingle nucleotide polymorphismen_US
dc.subjectsynapseen_US
dc.titleDe novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorderen_US
dc.typeArticleen_US

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