Recessive mutations in autism may behave like other rare recessive traits, thus allowing gene mapping using homozygosity analysis. Homozygosity mapping is frequently employed to isolate disease genes in families where the parents are known to be definably related, typically as cousins, which increases the risk for recessive disease [12]–[14]. However homozygous recessive “founder” mutations are also common in patients whose parents share only distant ancestry, common ethnicity, or in some cases no apparent ancestry at all [15], and population analysis of runs of homozygosity has been used to define genomic loci that may harbor such mutations in diseases characterized by genetic heterogeneity [16]–[18]. Here we surveyed the mutational spectrum in individuals with autism from nonconsanguineous populations who were selected for the high degree of homozygosity in the genome, since high levels of homozygosity suggest distant or cryptic shared ancestry of the parents. We identified several patients with potentially new autism mutations, and found that a surprising number of these mutations occurred in genes that are regulated by neuronal depolarization.
