| Autor: |
Christine Stevens, Michael E. Zwick, Deepthi Rajagopalan, Mara Parellada, David J. Cutler, Li-San Wang, Norio Ozaki, Jinlu Cai, Lauren A. Weiss, Patricia Jiménez González, Jeffrey C. Barrett, Silvia De Rubeis, Helena Kilpinen, Alexander Kolevzon, Timothy W. Yu, Michael John Owen, Geraldine Dawson, Martin Schulte-Rüther, Jeremy R. Parr, Aarno Palotie, Eftichia Duketis, Lambertus Klei, Irene Lee, Bridget A. Fernandez, Aniko Sabo, Matthew W. State, Sarah Curran, Lucy Crooks, Chad M. Schafer, Avi Ma'ayan, Stephen Sanders, Evan T. Geller, Monica Biscaldi, Stephen W. Scherer, Christopher S. Poultney, Mark J. Daly, Patrick Bolton, Kaija Puura, Maria H. Chahrour, Michael Gill, Li Liu, Louise Gallagher, Ryan K. C. Yuen, Jack A. Kosmicki, Abraham Reichenberg, Christine M. Freitag, Shaun Purcell, Andreas G. Chiocchetti, Peter Szatmari, Sabine M. Klauck, Shih-Chen Fu, Christian R. Marshall, Joseph D. Buxbaum, Tarjinder Singh, Bernie Devlin, Chiao-Feng Lin, A. Ercument Cicek, Karola Rehnström, Pamela Sklar, Otto Valladares, Michael Sachse, Terho Lehtimäki, R. Sean Hill, Arthur P. Goldberg, A. Jeremy Willsey, Jing Lei, Branko Aleksic, Menachem Fromer, Yan Kou, Jessica M. Brownfeld, Annette Voran, Kathryn Roeder, Gerard D. Schellenberg, David Skuse, Thomas Lehner, Hilary Coon, Benjamin M. Neale, Iuliana Ionita-Laza, Kristiina Tammimies, Stephen J. Guter, Christopher A. Walsh, James S. Sutcliffe, Xin-Xin He, Alison L. McInnes, Emily L. Crawford, Nicholas G. Campbell, Angel Carracedo, R. Susan Walker, Edwin H. Cook, Kaitlin E. Samocha, Christina M. Hultman |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Nature |
| ISSN: |
1476-4687
0028-0836 |
| Popis: |
The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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