Our copy number analysis, linkage, and resequencing together support other recent studies (3, 4, 6) suggesting that autism is highly heterogeneous genetically, but our data further suggest that homozygosity mapping provides an important approach to dissect this heterogeneity. We show that individuals with related parents are more likely to have inherited causes of disease, likely autosomal and recessive, and that these pedigrees allow mapping of loci from small numbers of families. Such families can also provide linkage evidence to support the identification of mutations, both coding and noncoding. Genes that act in a recessive manner may make good candidates for future analysis in association or resequencing studies, because they may show interactions with other nonlinked mutations (38). Our data implicating noncoding elements in patients with shared ancestry, as well as the heterozygous nonsense changes in patients without shared ancestry, suggest that loss of proper regulation of gene dosage may be an important genetic mechanism in autism. This possibility is also strongly supported by the numerous heterozygous CNVs found in patients from noncon-sanguineous pedigrees (4, 6).
