Whole-Exome Sequencing and Homozygosity Analysis Implicate Depolarization-Regulated Neuronal Genes in Autism
作者： Maria H Chahrour , Timothy W Yu , Elaine T Lim , Bulent Ataman , Michael E Coulter
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摘要: Although autism has a clear genetic component, the high heterogeneity of disorder been challenge for identification causative genes. We used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence distant shared ancestry, suggesting potentially recessive mutations. Whole-exome sequencing 16 revealed validated homozygous, pathogenic mutations segregated perfectly with disease in 4/16 families. The candidate genes (UBE3B, CLTCL1, NCKAP5L, ZNF18) encode proteins involved proteolysis, GTPase-mediated signaling, cytoskeletal organization, and other pathways. Furthermore, neuronal depolarization regulated transcription these genes, potential activity-dependent roles neurons. present multidimensional strategy filtering whole-exome sequence data find autism, which may have broader applicability complex, heterogeneous disorders.
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