We also examined the effect on the size of the candidate gene list when analyzing the exomes of affected individuals in different pairwise or three-way combinations, and the potential consequences of genetic heterogeneity by relaxing selection criteria such that only a subset of the exomes of affected individuals were required to contain novel variants in a given gene for it to be considered as a candidate gene (Table 3). Heterogeneity clearly increases the number of candidate genes that must be considered under any fixed number of exomes analyzed. However, this likely can be overcome by the inclusion of a greater number of cases with mutations in the same gene.
