Although the large size of linked loci precluded systematic gene sequencing in most cases, we were surprised to see that several consanguineous pedigrees showed large, rare, inherited homozygous deletions within linked regions, some of which are very likely causative mutations (Figs. 1 and 2 and table S5). Such deletions were present in 5 of 78 consanguineous pedigrees (6.4%) and ranged in size from 18 thousand base pairs (kbp) to > 880 kbp. For example, patient AU-3101, a boy diagnosed with autistic disorder and seizures, demonstrated a 74-cM segment of identity by descent (IBD) on chromosome 3q (lod score = 1.45) (Fig. 1), with an ~886-kbp homozygous deletion within 3q24. The deletion is hemizygous in both parents and an unaffected sibling (hence inherited from a common grandparent or more distant ancestor) but was not present in any of the other 393 samples from our autism pedigrees, nor in 184 Middle Eastern control chromosomes, nor in 2200 samples from the Autism Genetic Resource Exchange (AGRE) repository (www.agre.org). This deletion was confirmed using Agilent oligo arrays (fig. S2) and polymerase chain reaction (PCR)
