학술논문
Genomic architecture of autism from comprehensive whole-genome sequence annotation.
Document Type
article
Author
Trost, Brett; Thiruvahindrapuram, Bhooma; Chan, Ada; Engchuan, Worrawat; Higginbotham, Edward; Howe, Jennifer; Loureiro, Livia; Reuter, Miriam; Roshandel, Delnaz; Whitney, Joe; Zarrei, Mehdi; Bookman, Matthew; Somerville, Cherith; Shaath, Rulan; Abdi, Mona; Aliyev, Elbay; Patel, Rohan; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Hamdan, Omar; Kaur, Gaganjot; Wang, Zhuozhi; MacDonald, Jeffrey; Wei, John; Sung, Wilson; Lamoureux, Sylvia; Hoang, Ny; Selvanayagam, Thanuja; Deflaux, Nicole; Geng, Melissa; Ghaffari, Siavash; Bates, John; Young, Edwin; Ding, Qiliang; Shum, Carole; DAbate, Lia; Bradley, Clarrisa; Rutherford, Annabel; Aguda, Vernie; Apresto, Beverly; Chen, Nan; Desai, Sachin; Du, Xiaoyan; Fong, Matthew; Pullenayegum, Sanjeev; Samler, Kozue; Wang, Ting; Ho, Karen; Paton, Tara; Pereira, Sergio; Herbrick, Jo-Anne; Wintle, Richard; Fuerth, Jonathan; Noppornpitak, Juti; Ward, Heather; Magee, Patrick; Al Baz, Ayman; Kajendirarajah, Usanthan; Kapadia, Sharvari; Vlasblom, Jim; Valluri, Monica; Green, Joseph; Seifer, Vicki; Quirbach, Morgan; Rennie, Olivia; Kelley, Elizabeth; Masjedi, Nina; Lord, Catherine; Szego, Michael; Zawati, Man; Lang, Michael; Strug, Lisa; Marshall, Christian; Costain, Gregory; Calli, Kristina; Iaboni, Alana; Yusuf, Afiqah; Ambrozewicz, Patricia; Gallagher, Louise; Amaral, David; Brian, Jessica; Elsabbagh, Mayada; Georgiades, Stelios; Messinger, Daniel; Sebat, Jonathan; Sjaarda, Calvin; Smith, Isabel; Szatmari, Peter; Zwaigenbaum, Lonnie; Kushki, Azadeh; Frazier, Thomas; Vorstman, Jacob; Fakhro, Khalid; Fernandez, Bridget; Lewis, M; Weksberg, Rosanna; Fiume, Marc; Yuen, Ryan; Anagnostou, Evdokia; Sondheimer, Neal
Source
Cell. 185(23)
Subject
Language
Abstract
Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.