Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
Yuen, Ryan K C; Merico, Daniele; Bookman, Matt; Howe, Jennifer L.; Thiruvahindrapuram, Bhooma; Patel, Rohan V.; Whitney, Joe; Deflaux, Nicole; Bingham, Jonathan; Wang, Zhuozhi; Pellecchia, Giovanna; Buchanan, Janet A.; Walker, Susan; Marshall, Christian R.; Uddin, Mohammed; Zarrei, Mehdi; Deneault, Eric; D'Abate, Lia; Chan, Ada J S; Koyanagi, Stephanie; Paton, Tara; Pereira, Sergio L.; Hoang, Ny; Engchuan, Worrawat; Higginbotham, Edward J.; Ho, Karen; Lamoureux, Sylvia; Li, Weili; MacDonald, Jeffrey R.; Nalpathamkalam, Thomas; Sung, Wilson W L; Tsoi, Fiona J.; Wei, John; Xu, Lizhen; Tasse, Anne Marie; Kirby, Emily; Van Etten, William; Twigger, Simon; Roberts, Wendy; Drmic, Irene; Jilderda, Sanne; Modi, Bonnie Mackinnon; Kellam, Barbara; Szego, Michael; Cytrynbaum, Cheryl; Weksberg, Rosanna; Zwaigenbaum, Lonnie; Woodbury-Smith, Marc; Brian, Jessica; Senman, Lili; Iaboni, Alana; Doyle-Thomas, Krissy; Thompson, Ann; Chrysler, Christina; Leef, Jonathan; Savion-Lemieux, Tal; Smith, Isabel M.; Liu, Xudong; Nicolson, Rob; Seifer, Vicki; Fedele, Angie; Cook, Edwin H.; Dager, Stephen; Estes, Annette; Gallagher, Louise; Malow, Beth A.; Parr, Jeremy R.; Spence, Sarah J.; Vorstman, Jacob; Frey, Brendan J.; Robinson, James T.; Strug, Lisa J.; Fernandez, Bridget A.; Elsabbagh, Mayada; Carter, Melissa T.; Hallmayer, Joachim; Knoppers, Bartha M.; Anagnostou, Evdokia; Szatmari, Peter; Ring, Robert H.; Glazer, David; Pletcher, Mathew T.; Scherer, Stephen W.
(2017) Nature Neuroscience, volume 20, issue 4, pp. 602 - 611
(Article)
Abstract
We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and
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through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.
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Keywords: Autism spectrum disorders, Next-generation sequencing, General Neuroscience, Journal Article
ISSN: 1097-6256
Publisher: Nature Publishing Group
Note: Funding Information: This work was funded by Autism Speaks, Autism Speaks Canada, the Canadian Institute for Advanced Research, the University of Toronto McLaughlin Centre, Genome Canada/Ontario Genomics Institute, the Government of Ontario, the Canadian Institutes of Health Research (CIHR), NeuroDevNet, Ontario Brain Institute, the Catherine and Maxwell Meighen Foundation and The Hospital for Sick Children Foundation. Special thanks to B. and (the late) S. Wright for their vision in helping to conceptualize and develop this project and to foundational philanthropic supporters C. Dolan, G. Gund, B. Marcus, V. and J. Morgan and S. Wise. R.K.C.Y. is funded by the CIHR Postdoctoral Fellowship, NARSAD Young Investigator award and Thrasher Early Career Award. R.W. is funded by the Ontario Brain Institute and NeuroDevNet. M.U. is funded by the Banting Postdoctoral Fellowship. M.W. is funded by a CIHR (Institute of Genetics) Clinical Investigatorship Award. L.Z. is funded by the Stollery Children's Hospital Foundation Chair in Autism Research. P.S. is funded by the Patsy and Jamie Anderson Chair in Child and Youth Mental Health. B.M.K. is funded by the Canada Research Chair in Law and Medicine. S.W.S. is funded by the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. Publisher Copyright: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
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