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Article: Functional impact of global rare copy number variation in autism spectrum disorders

TitleFunctional impact of global rare copy number variation in autism spectrum disorders
Authors
Pinto, DPagnamenta, ATKlei, LAnney, RMerico, DRegan, RConroy, JMagalhaes, TRCorreia, CAbrahams, BSAlmeida, JBacchelli, EBader, GDBailey, AJBaird, GBattaglia, ABerney, TBolshakova, NBölte, SBolton, PFBourgeron, TBrennan, SBrian, JBryson, SECarson, ARCasallo, GCasey, JChung, BHYCochrane, LCorsello, CCrawford, ELCrossett, ACytrynbaum, CDawson, GDe Jonge, MDelorme, RDrmic, IDuketis, EDuque, FEstes, AFarrar, PFernandez, BAFolstein, SEFombonne, EFreitag, CMGilbert, JGillberg, CGlessner, JTGoldberg, JGreen, AGreen, JGuter, SJHakonarson, HHeron, EAHill, MHolt, RHowe, JLHughes, GHus, VIgliozzi, RKim, CKlauck, SMKolevzon, AKorvatska, OKustanovich, VLajonchere, CMLamb, JALaskawiec, MLeboyer, MLe Couteur, ALeventhal, BLLionel, ACLiu, XQLord, CLotspeich, LLund, SCMaestrini, EMahoney, WMantoulan, CMarshall, CRMcconachie, HMcdougle, CJMcgrath, JMcmahon, WMMerikangas, AMigita, OMinshew, NJMirza, GKMunson, JNelson, SFNoakes, CNoor, ANygren, GOliveira, GPapanikolaou, KParr, JRParrini, BPaton, TPickles, APilorge, MPiven, JPonting, CPPosey, DJPoustka, APoustka, FPrasad, ARagoussis, JRenshaw, KRickaby, JRoberts, WRoeder, KRoge, BRutter, MLBierut, LJRice, JPSalt, JSansom, KSato, DSegurado, RSequeira, AFSenman, LShah, NSheffield, VCSoorya, LSousa, IStein, OSykes, NStoppioni, VStrawbridge, CTancredi, RTansey, KThiruvahindrapduram, BThompson, APThomson, STryfon, ATsiantis, JVan Engeland, HVincent, JBVolkmar, FWallace, SWang, KWang, ZWassink, THWebber, CWeksberg, RWing, KWittemeyer, KWood, SWu, JYaspan, BLZurawiecki, DZwaigenbaum, LBuxbaum, JDCantor, RMCook, EHCoon, HCuccaro, MLDevlin, BEnnis, SGallagher, LGeschwind, DHGill, MHaines, JLHallmayer, JMiller, JMonaco, APNurnberger Jr, JIPaterson, ADPericakVance, MASchellenberg, GDSzatmari, PVicente, AMVieland, VJWijsman, EMScherer, SWSutcliffe, JSBetancur, C
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2010, v. 466 n. 7304, p. 368-372 How to Cite?
AbstractThe autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability 2. Although ASDs are known to be highly heritable ( ∼90%) 3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (<1%frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P=0.012), especially so for loci previously implicated in either ASDand/or intellectual disability (1.69 fold, P=3.4×310 -4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways. © 2010 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/170439
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPinto, Den_US
dc.contributor.authorPagnamenta, ATen_US
dc.contributor.authorKlei, Len_US
dc.contributor.authorAnney, Ren_US
dc.contributor.authorMerico, Den_US
dc.contributor.authorRegan, Ren_US
dc.contributor.authorConroy, Jen_US
dc.contributor.authorMagalhaes, TRen_US
dc.contributor.authorCorreia, Cen_US
dc.contributor.authorAbrahams, BSen_US
dc.contributor.authorAlmeida, Jen_US
dc.contributor.authorBacchelli, Een_US
dc.contributor.authorBader, GDen_US
dc.contributor.authorBailey, AJen_US
dc.contributor.authorBaird, Gen_US
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dc.contributor.authorBerney, Ten_US
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dc.contributor.authorBolton, PFen_US
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dc.contributor.authorBrennan, Sen_US
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dc.contributor.authorBryson, SEen_US
dc.contributor.authorCarson, ARen_US
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dc.contributor.authorChung, BHYen_US
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dc.contributor.authorSenman, Len_US
dc.contributor.authorShah, Nen_US
dc.contributor.authorSheffield, VCen_US
dc.contributor.authorSoorya, Len_US
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dc.contributor.authorStein, Oen_US
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dc.contributor.authorStoppioni, Ven_US
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dc.contributor.authorWu, Jen_US
dc.contributor.authorYaspan, BLen_US
dc.contributor.authorZurawiecki, Den_US
dc.contributor.authorZwaigenbaum, Len_US
dc.contributor.authorBuxbaum, JDen_US
dc.contributor.authorCantor, RMen_US
dc.contributor.authorCook, EHen_US
dc.contributor.authorCoon, Hen_US
dc.contributor.authorCuccaro, MLen_US
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dc.contributor.authorGeschwind, DHen_US
dc.contributor.authorGill, Men_US
dc.contributor.authorHaines, JLen_US
dc.contributor.authorHallmayer, Jen_US
dc.contributor.authorMiller, Jen_US
dc.contributor.authorMonaco, APen_US
dc.contributor.authorNurnberger Jr, JIen_US
dc.contributor.authorPaterson, ADen_US
dc.contributor.authorPericakVance, MAen_US
dc.contributor.authorSchellenberg, GDen_US
dc.contributor.authorSzatmari, Pen_US
dc.contributor.authorVicente, AMen_US
dc.contributor.authorVieland, VJen_US
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dc.date.accessioned2012-10-30T06:08:46Z-
dc.date.available2012-10-30T06:08:46Z-
dc.date.issued2010en_US
dc.identifier.citationNature, 2010, v. 466 n. 7304, p. 368-372en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://hdl.handle.net/10722/170439-
dc.description.abstractThe autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability 2. Although ASDs are known to be highly heritable ( ∼90%) 3, the underlying genetic determinants are still largely unknown.Hereweanalysed the genome-wide characteristics of rare (<1%frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P=0.012), especially so for loci previously implicated in either ASDand/or intellectual disability (1.69 fold, P=3.4×310 -4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways. © 2010 Macmillan Publishers Limited. All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_US
dc.relation.ispartofNatureen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshCell Movementen_US
dc.subject.meshChilden_US
dc.subject.meshChild Development Disorders, Pervasive - Genetics - Pathology - Physiopathologyen_US
dc.subject.meshCytoprotectionen_US
dc.subject.meshDna Copy Number Variations - Geneticsen_US
dc.subject.meshEurope - Ethnologyen_US
dc.subject.meshGene Dosage - Geneticsen_US
dc.subject.meshGenetic Predisposition To Disease - Geneticsen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.subject.meshHumansen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshSocial Behavioren_US
dc.titleFunctional impact of global rare copy number variation in autism spectrum disordersen_US
dc.typeArticleen_US
dc.identifier.emailChung, BHY:bhychung@hku.hken_US
dc.identifier.authorityChung, BHY=rp00473en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/nature09146en_US
dc.identifier.pmid20531469-
dc.identifier.pmcidPMC3021798-
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dc.identifier.volume466en_US
dc.identifier.issue7304en_US
dc.identifier.spage368en_US
dc.identifier.epage372en_US
dc.identifier.eissn1476-4687-
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dc.identifier.scopusauthoridLamb, JA=7201524789en_US
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dc.identifier.scopusauthoridLeboyer, M=7005287140en_US
dc.identifier.scopusauthoridLe Couteur, A=6603046189en_US
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dc.identifier.scopusauthoridRoberts, W=7403316556en_US
dc.identifier.scopusauthoridBacchelli, E=6507685887en_US
dc.identifier.scopusauthoridRoeder, K=7103005216en_US
dc.identifier.citeulike7285777-

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