Functional impact of global rare copy number variation in autism spectrum disorders

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Title: Functional impact of global rare copy number variation in autism spectrum disorders
Authors: Pinto, Dalila
Pagnamenta, Alistair T.
Klei, Lambertus
Regan, Regina
Conroy, Judith
Casey, Jillian
Green, Andrew
Segurado, Ricardo
Shah, Naisha
Ennis, Sean
et al.
Permanent link: http://hdl.handle.net/10197/4381
Date: 15-Jul-2010
Abstract: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable (~90%)3, the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 × 10-4). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
Type of material: Journal Article
Publisher: Nature Publishing Group
Keywords: Autism;Spectrum disorders
DOI: 10.1038/nature09146
Language: en
Status of Item: Peer reviewed
Appears in Collections:Public Health, Physiotherapy and Sports Science Research Collection

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