News Finding: New today!  The convergence of genes &amp; pathways dysregulated in #autism spectrum disorders.    #OA
Paper Finding: Our data (1) confirm excess burden of genome-wide rare genic CNVs in an independent set of ASD subjects versus control subjects; (2) further reveal an extreme degree of etiological heterogeneity (36 different genetic loci were found among 82 individuals with pathogenic CNVs); (3) confirm the contribution of de novo CNVs to the etiology of autism and highlight the contribution of inherited pathogenic imbalances (36%); (4) show an increased proportion of females among carriers of highly penetrant pathogenic CNVs, as well as among carriers of deletions affecting FMRP targets; show no significant difference in the frequency of de novo CNVs between simplex and multiplex families; show that both deletions and duplications involving FMRP targets and PSD genes increase ASD risk; (7) show evidence of multigene contributions to ASD; show that ASD-associated deletions impair synapse function and neurodevelopmental processes; (9) implicate chromatin and transcription regulation genes in ASD in a network analysis of de novo CNVs; and show that genes affected by de novo CNVs and de novo LoF SNVs converge on functional gene networks.
News Context: New today!  The convergence of genes &amp; pathways dysregulated in #autism spectrum disorders.    #OA
Paper Context: Thus, despite little overlap in genes, the strong interconnectedness between the resulting networks identifies pathways through which the effects of distinct mutations might converge. Our data (1) confirm excess burden of genome-wide rare genic CNVs in an independent set of ASD subjects versus control subjects; (2) further reveal an extreme degree of etiological heterogeneity (36 different genetic loci were found among 82 individuals with pathogenic CNVs); (3) confirm the contribution of de novo CNVs to the etiology of autism and highlight the contribution of inherited pathogenic imbalances (36%); (4) show an increased proportion of females among carriers of highly penetrant pathogenic CNVs, as well as among carriers of deletions affecting FMRP targets; show no significant difference in the frequency of de novo CNVs between simplex and multiplex families; show that both deletions and duplications involving FMRP targets and PSD genes increase ASD risk; (7) show evidence of multigene contributions to ASD; show that ASD-associated deletions impair synapse function and neurodevelopmental processes; (9) implicate chromatin and transcription regulation genes in ASD in a network analysis of de novo CNVs; and show that genes affected by de novo CNVs and de novo LoF SNVs converge on functional gene networks. Importantly, when considering highly penetrant pathogenic CNVs, we found a 2:1 male-to-female ratio (deviating from the overall ratio of 6:1 in the study sample).