Homozygosity mapping in consanguineous autism pedigrees suggested considerable genetic heterogeneity, implicating several genetic loci, with limited overlap between pedigrees. Using the Affymetrix Gene-Chip Human Mapping 500K SNP arrays, a locus-exclusionary approach was taken assuming a model of autosomal recessive inheritance and high penetrance. Several single families showed one or two loci with strong support for linkage [multipoint logarithm of the odds ratio for linkage (lod) scores ranging from 2.4 to 2.96] (table S4), corroborated by microsatellite analysis. Potentially linked loci were generally nonoverlapping between families, consistent with genetic heterogeneity, although two families shared linkage to an overlapping region of chromosome 2q (AU-4500, lod = 2.41, and AU-4200, lod = 1.81) that has been previously implicated in other autism linkage studies (27). The higher lod scores from single families, although not achieving genome-wide significance, are comparable to the highest lod scores achieved by pooling hundreds of nonconsanguineous pedigrees (3, 4, 27).
