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dc.contributor.authorNeale, Benjamin Michael
dc.contributor.authorKou, Yan
dc.contributor.authorLiu, Li
dc.contributor.authorMa'ayan, Avi
dc.contributor.authorSamocha, Kaitlin Elisabeth
dc.contributor.authorSabo, Aniko
dc.contributor.authorLin, Chiao-Feng
dc.contributor.authorStevens, Christine
dc.contributor.authorWang, Li-San
dc.contributor.authorMakarov, Vladimir
dc.contributor.authorPolak, Pazi Penchas
dc.contributor.authorYoon, Seungtai
dc.contributor.authorMaguire, Jared
dc.contributor.authorCrawford, Emily L.
dc.contributor.authorCampbell, Nicholas G.
dc.contributor.authorGeller, Evan T.
dc.contributor.authorValladares, Otto
dc.contributor.authorShafer, Chad
dc.contributor.authorLiu, Han
dc.contributor.authorZhao, Tuo
dc.contributor.authorCai, Guiqing
dc.contributor.authorLihm, Jayon
dc.contributor.authorDannenfelser, Ruth
dc.contributor.authorJabado, Omar
dc.contributor.authorPeralta, Zuleyma
dc.contributor.authorNagaswamy, Uma
dc.contributor.authorMuzny, Donna
dc.contributor.authorReid, Jeffrey G.
dc.contributor.authorNewsham, Irene
dc.contributor.authorWu, Yuanqing
dc.contributor.authorLewis, Lora
dc.contributor.authorHan, Yi
dc.contributor.authorVoight, Benjamin F.
dc.contributor.authorLim, Elaine
dc.contributor.authorRossin, Elizabeth Jeffries
dc.contributor.authorKirby, Andrew
dc.contributor.authorFlannick, Jason A.
dc.contributor.authorFromer, Menachem
dc.contributor.authorShakir, Khalid
dc.contributor.authorFennell, Tim
dc.contributor.authorGarimella, Kiran
dc.contributor.authorBanks, Eric
dc.contributor.authorPoplin, Ryan
dc.contributor.authorGabriel, Stacey
dc.contributor.authorDePristo, Mark
dc.contributor.authorWimbish, Jack R.
dc.contributor.authorBoone, Braden E.
dc.contributor.authorLevy, Shawn E.
dc.contributor.authorBetancur, Catalina
dc.contributor.authorSunyaev, Shamil R.
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBuxbaum, Joseph D.
dc.contributor.authorCook, Edwin H.
dc.contributor.authorDevlin, Bernie
dc.contributor.authorGibbs, Richard A.
dc.contributor.authorRoeder, Kathryn
dc.contributor.authorSchellenberg, Gerard D.
dc.contributor.authorSutcliffe, James S.
dc.contributor.authorDaly, Mark Joseph
dc.date.accessioned2013-12-10T16:34:43Z
dc.date.issued2013
dc.identifier.citationNeale, Benjamin M., Yan Kou, Li Liu, Avi Ma'ayan, Kaitlin E. Samocha, Aniko Sabo, Chiao-Feng Lin, et al. 2013. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 485(7397): 242-245.en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11365694
dc.description.abstractAutism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there is significantly enriched connectivity among the proteins encoded by genes harboring de novo missense or nonsense mutations, and excess connectivity to prior ASD genes of major effect, suggesting a subset of observed events are relevant to ASD risk. The small increase in rate of de novo events, when taken together with the connections among the proteins themselves and to ASD, are consistent with an important but limited role for de novo point mutations, similar to that documented for de novo copy number variants. Genetic models incorporating these data suggest that the majority of observed de novo events are unconnected to ASD, those that do confer risk are distributed across many genes and are incompletely penetrant (i.e., not necessarily causal). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors.en_US
dc.language.isoen_USen_US
dc.relation.isversionofdoi:10.1038/nature11011en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613847/pdf/en_US
dash.licenseLAA
dc.titlePatterns and rates of exonic de novo mutations in autism spectrum disordersen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalNatureen_US
dash.depositing.authorNeale, Benjamin Michael
dc.date.available2013-12-10T16:34:43Z
dc.identifier.doi10.1038/nature11011*
dash.authorsorderedfalse
dash.contributor.affiliatedShakir, Khalid
dash.contributor.affiliatedRossin, Elizabeth
dash.contributor.affiliatedFlannick, Jason
dash.contributor.affiliatedSamocha, Kaitlin E.
dash.contributor.affiliatedNeale, Benjamin
dash.contributor.affiliatedPolak, Paz
dash.contributor.affiliatedSunyaev, Shamil
dash.contributor.affiliatedDaly, Mark


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