| http://purl.uniprot.org/citations/22495309 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22495309 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22495309 | http://www.w3.org/2000/01/rdf-schema#comment | "It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature10989"xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature10989"xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Eichler E.E."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Eichler E.E."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Ko A."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Ko A."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Levy R."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Levy R."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Lee C."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Lee C."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Shendure J."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Shendure J."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Nickerson D.A."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Nickerson D.A."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Smith J.D."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Smith J.D."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Rieder M.J."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Rieder M.J."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "O'Roak B.J."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "O'Roak B.J."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Reilly B."xsd:string |
| http://purl.uniprot.org/citations/22495309 | http://purl.uniprot.org/core/author | "Reilly B."xsd:string |