Subsequent studies in larger samples have confirmed a high (5–10%) rate of de novo CNVs in ASD and further elucidated the extent of genetic heterogeneity in ASD (Itsara et al., 2010; Levy et al., 2011; Marshall et al., 2008; Pinto et al., 2010; Sanders et al., 2011). A detailed analysis of large ASD cohorts of simplex autism cases using very high resolution arrays was recently performed by two independent groups (Levy et al., 2011; Sanders et al., 2011). These studies reported that the burden of rare de novo CNVs is significantly greater in simplex cases (5.8–7.9%) than in unaffected siblings (1.7–1.9%) with regard to the total number of events, the size of each event, and their gene content. Affected cases on average had 16-fold excess of genes impacted by de novo CNVs compared to healthy sibs (30-fold for deletions). Based on the number of recurrent de novo CNVs and the estimated proportion of de novo CNVs ascertained, Levy et al estimated around 250–300 target loci for ASDs and Sanders et al. estimated between 130–234 loci.
