De Novo Insertions and Deletions of Predominantly Paternal Origin Are   Associated with Autism Spectrum Disorder

doi:10.1016/j.celrep.2014.08.068

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	De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder
	Dong, Shan ; Walker, Michael F. ; Carriero, Nicholas J. ; DiCola, Michael ; Willsey, A. Jeremy ; Ye, Adam Y. ; Waqar, Zainulabedin ; Gonzalez, Luis E. ; Overton, John D. ; Frahm, Stephanie ; Keaney, John F., III ; Teran, Nicole A. ; Dea, Jeanselle ; Mandell, Jeffrey D. ; Bal, Vanessa Hus ; Sullivan, Catherine A. ; DiLullo, Nicholas M. ; Khalil, Rehab O. ; Gockley, Jake ; Yuksel, Zafer ; Sertel, Sinem M. ; Ercan-Sencicek, A. Gulhan ; Gupta, Abha R. ; Mane, Shrikant M. ; Sheldon, Michael ; Brooks, Andrew I. ; Roeder, Kathryn ; Devlin, Bernie ; State, Matthew W. ; We
刊名	cell reports
	2014
关键词	ZONE PROTEIN RIM1-ALPHA MUTATIONS NETWORKS GENES
DOI	10.1016/j.celrep.2014.08.068
英文摘要	Whole-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 3 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.; Cell Biology; SCI(E); PubMed; 6; ARTICLE; matthew.state@ucsf.edu; weilp@mail.cbi.pku.edu.cn; stephan.sanders@ucsf.edu; 1; 16-23; 9
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/188785]
专题	生命科学学院
推荐引用方式 GB/T 7714	Dong, Shan,Walker, Michael F.,Carriero, Nicholas J.,et al. De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder[J]. cell reports,2014.
APA	Dong, Shan.,Walker, Michael F..,Carriero, Nicholas J..,DiCola, Michael.,Willsey, A. Jeremy.,...&We.(2014).De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder.cell reports.
MLA	Dong, Shan,et al."De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder".cell reports (2014).