Autism genome-wide copy number variation reveals ubiquitin and neuronal genes

作者：Joseph Glessner, Kai Wang, Guiqing Cai, Olena Korvatska, Cecilia E. Kim, Shawn Wood, Haitao Zhang, Annette Estes, Camille W. Brune, Jonathan P. Bradfield, Marcin Imieliński, Edward C. Frackelton, Jennifer Reichert, Emily L. Crawford, Jeffrey Munson, Patrick Sleiman, Rosetta Chiavacci, Kiran Annaiah, Kelly Thomas, Cuiping Hou, Wendy Glaberson, James H. Flory, F. George Otieno, Maria Garris, Latha Soorya, Lambertus Klei, Joseph Piven, Kacie J. Meyer, Evdokia Anagnostou, Takeshi Sakurai, Rachel M. Game, Danielle S. Rudd, Danielle Zurawiecki, Christopher J. McDougle, Lea K. Davis, Judith Miller, David J. Posey, Shana M. Michaels, Alexander Kolevzon, Jeremy M. Silverman, Raphael Bernier, Susan E. Levy, Robert T. Schultz, Géraldine Dawson, Thomas Owley, William M. McMahon, Thomas H. Wassink, John A. Sweeney, John I. Nürnberger, Hilary Coon, James S. Sutcliffe, Nancy J. Minshew, Struan F.A. Grant, Maja Bućan, Edwin H. Cook, Joseph D. Buxbaum, Bernie Devlin, Gerard D. Schellenberg, Håkon Håkonarson · 发表于：Nature · 年份：2009 · DOI：10.1038/nature07953 · 被引用次数：1449 · 研究领域：Genomic variations and chromosomal abnormalities、Autism Spectrum Disorder Research、Genetics and Neurodevelopmental Disorders

Several lines of evidence point to genetic involvement in autism spectrum disorders (ASDs), neurodevelopmental and neuropsychiatric disorders characterized by impaired verbal communication and social interaction. The clinical and genetic complexities of the condition make it difficult to identify susceptibility factors, but two related studies now present robust evidence for a genetic involvement. The first, a genome-wide association study, identifies six single-nucleotide polymorphisms strongly associated with autism. These variants lie between two genes encoding neuronal cell-adhesion molecules (cadherins 9 and 10), suggesting possible involvement in ASD pathogenesis. The second study used copy number variation screens to identify genetic variants in two major gene pathways in children with ASDs. The changes are in the ubiquitin pathway, which has previously been associated with neurological disease, and in genes for neuronal cell-adhesion molecules. Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social and communication skills. Accumulating evidence suggests a genetic component to ASDs, and here a two-stage, genome-wide approach is used to identify candidate genomic loci enriched in ASD cases. The majority of these loci are found to be involved in neuronal adhesion and ubiquitin degradation, suggesting novel susceptibility mechanisms. Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex ...