The likelihood of observing multiple independent de novo events of a given type for a given sample size in an ASD risk-conferring gene was modeled using gene size and GC content (derived from the full set of brain-expressed RefSeq genes) and the observed rate of brain-expressed de novo variants in probands and siblings. These values were then used to evaluate the number of genes contributing to ASD showing two or more variants of the specified type (Fig. 2); comparing this to the number of genes with similar events not carrying ASD risk gave the liklihood of the specified pattern reflecting association with ASD. The simulation was run through 150,000 iterations across a range of samples sizes and multiple models of locus heterogeneity (Supplementary Information).
