It is striking that while we replicate findings of elevated rates of rare de novo CNVs in simplex families (5.8% of probands versus 1.7% in siblings), the percentage of the cohort carrying these events is the same magnitude as that seen previously. This is despite the intensive focus on the ascertainment of simplex quartets and the 10-fold increase in probe density since the earliest studies of ASD. We believe these results are best explained by the particular contribution of large genic de novo variants given the results of our analysis of gene number, CNV size, and affected status (Figure 3), and the observation of generally consistent results over time despite steadily increasing detection resolution.
