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Table 1 Whole-exome gene finding sequencing studies that reveal common and rare variants associated with ASD

From: Autism genetics: searching for specificity and convergence

References Participants De novovariant characteristics Single genes implicated Novel findings Trends
Neale et al. 2012 [24] 175 families*, simplex/multiplex and trios. 175 cases, 350 parents Equal frequency of de novo mutations in cases and control KATNAL2 and CHD8 harbor de novo mutations in cases, none found in controls (935 cases versus 870 controls; targeted exome sequencing) Significantly enriched number of protein interactions among genes with missense or nonsense de novo mutations Greater paternal and maternal age correlates with greater number of de novo mutations
O'Roak et al. 2012 [22] 209 families (SSC), simplex, trios and quads. 209 cases, 418 parents, 50 unaffected sibs Equal frequency of de novo mutation in cases and controls ASD cases harbor protein-disrupting mutations in GRIN2B, LAMC3, and SCN1A (mutation screening; 1,703 ASD cases, 744 controls) and CHD8 and NTNG1 (recurrent) Genes with de novo mutations that cause missense or nonsense mutations form a β-catenin/chromatin remodeling protein network enriched for ASD candidate genes 4:1 paternal origin of de novo mutations. Greater paternal age correlates with greater number of de novo SNVs
Sanders et al. 2012 [25] 238 families (SSC), simplex, trios and quads. 238 cases, 476 parents, 200 unaffected sibs Equal frequency of de novo mutation in cases and controls SCN2A significantly associated with ASD. KATNAL2, CHD8, and SCN2A significantly associated with ASD when combined with [22, 24] Significantly greater non-synonymous and nonsense de novo SNVs in cases than unaffected sibs (all genes and brain-expressed genes), OR 1.93 for non-synonymous to silent SNVs in cases versus unaffected sibs Greater paternal age correlates with greater number of de novo SNVs
Iossifov et al. 2012 [23] 343 families (SSC), simplex, quads. 343 cases, 686 parents, 343 unaffected sibs Equal frequency of de novo mutation in cases and controls KATNAL2, CHD8, SCN2A, DYRK1A, and POGZ significantly associated with ASD when combining all studies [2225] Twofold higher numbers of frame-shift, splice-site, and nonsense de novo mutations in cases than in unaffected sibs. Enriched number of gene-disrupting mutations in FMRP-associated genes ([23] alone and when combining data from all studies [2225]) Greater paternal and maternal age correlates with greater number of de novo mutations
  1. * Boston Autism Consortium