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Chunk #2 — Ascertainment of pedigrees with autism and recent shared ancestry

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Identifying autism loci and genes by tracing recent shared ancestry.
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An increased role for inherited factors in autism families with shared ancestry was also suggested by a low rate of de novo CNVs that segregated with disease, despite the use of two sensitive methods for detecting them: the Affymetrix Gene-Chip Human Mapping 500K single-nucleotide polymorphism (SNP) array, as well as bacterial artificial chromosome (BAC) comparative genomic hybridization (CGH) microarrays [principally an extensively validated, commercial microarray from Signature Genomics (see 22)]. Whereas rates of inherited CNVs (some potentially causative) were high in both the SNP and BAC arrays, ranging in size from 1.4 kb to 3.9 Mb (tables S2 and S3), overall rates of de novo CNVs that segregated with ASD were 0% in consanguineous multiplex (0 of 42 patients) and 1.9% in consanguineous simplex families (1 of 52 patients), which were considerably lower than reported for non-consanguineous families: 1.28% in 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