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) (fig. S3). The deletion completely removes c3orf58, which encodes an uncharacterized protein with a signal peptide that localizes to the Golgi (28). Moreover, the deletion is near the 5′ region of NHE9, such that only 60 to 85 kbp upstream of the transcription initiation site is spared. NHE9 (also known as SLC9A9) encodes a (Na+, K+)/H+ exchanger previously reported to have been disrupted in a pedigree with a developmental neuropsychiatric disorder and mild mental retardation (29). Of note, SNPs within NHE9 and less than 100 kb from c3orf58 were among the top 21 regions (P < 0.00001) in the human genome showing adaptive selection (i.e., evidence for recent evolutionary selection) in a recent genome-wide analysis (30). A second >300 kbp, linked, homozygous deletion (again not present in >2000 individuals other than this family) is closest to PCDH10 on 4q28 (Fig. 2 and table S5), which encodes a cadherin superfamily protein essential for normal forebrain axon outgrowth (31). Smaller deletions (also
