the HMCA overall versus 7.1% using representational oligonucleotide microarray analysis in autism (6) (chi-square = 4.438, df = 1, P < 0.02), or versus 27.5% (7) (chi-square = 17.733, df = 1, P < 0.01) using another BAC array in syndromic autism. A large study, using identical BAC arrays run in the same lab as our study, found 5.6% (84 of 1500) of patients referred to Signature Genomics with de novo or pathogenic CNVs (chi-square = 3.052, df = 1, P < 0.05) (25). The HMCA rate of de novo CNVs was similar to previously reported rates in multiplex pedigrees with autism [1.28% in the HMCA versus 2.6%, or 2 of 77, in multiplex autism (6), chi-square = 0.557, df = 1, P = 0.22] and in controls [1.28% HMCA versus 1.0%, or 2 of 196, in control subjects (6), chi-square = 0.001, df = 1, P = 0.49], despite the fact that the 500K platform used here has significantly higher coverage. The single large de novo CNV discovered was a 3-Mb deletion at 22q11.21, the velocardiofacial syndrome (VCFS) locus (encompassing all SNPs between rs432770 and rs1014626), which has been previously reported in autistic patients (26). The relatively reduced M/F
