1. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
- Author
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C Yuen RK, Merico D, Bookman M, L Howe J, Thiruvahindrapuram B, Patel RV, Whitney J, Deflaux N, Bingham J, Wang Z, Pellecchia G, Buchanan JA, Walker S, Marshall CR, Uddin M, Zarrei M, Deneault E, D'Abate L, Chan AJ, Koyanagi S, Paton T, Pereira SL, Hoang N, Engchuan W, Higginbotham EJ, Ho K, Lamoureux S, Li W, MacDonald JR, Nalpathamkalam T, Sung WW, Tsoi FJ, Wei J, Xu L, Tasse AM, Kirby E, Van Etten W, Twigger S, Roberts W, Drmic I, Jilderda S, Modi BM, Kellam B, Szego M, Cytrynbaum C, Weksberg R, Zwaigenbaum L, Woodbury-Smith M, Brian J, Senman L, Iaboni A, Doyle-Thomas K, Thompson A, Chrysler C, Leef J, Savion-Lemieux T, Smith IM, Liu X, Nicolson R, Seifer V, Fedele A, Cook EH, Dager S, Estes A, Gallagher L, Malow BA, Parr JR, Spence SJ, Vorstman J, Frey BJ, Robinson JT, Strug LJ, Fernandez BA, Elsabbagh M, Carter MT, Hallmayer J, Knoppers BM, Anagnostou E, Szatmari P, Ring RH, Glazer D, Pletcher MT, and Scherer SW
- Subjects
- Chromosome Aberrations, DNA Copy Number Variations, Humans, Mutagenesis, Insertional genetics, Phenotype, Polymorphism, Single Nucleotide genetics, Sequence Deletion genetics, Autism Spectrum Disorder genetics, Databases, Genetic, Genetic Predisposition to Disease genetics, Genome-Wide Association Study methods
- 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 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.- Published
- 2017
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