Identifying autism loci and genes by tracing recent shared ancestry by Morrow Eric M, Yoo Seung-Yun, Flavell Steven W, Kim Tae-Kyung, Lin Yingxi, Hill Robert Sean, Mukaddes Nahit M, Balkhy Soher, Gascon Generoso, Hashmi Asif, Al-Saad Samira, Ware Janice, Joseph Robert M, Greenblatt Rachel, Gleason Danielle, Ertelt Julia A, Apse Kira A, Bodell Adria, Partlow Jennifer N, Barry Brenda, Yao Hui, Markianos Kyriacos, Ferland Russell J, Greenberg Michael E, Walsh Christopher A in Science (New York, N.Y.) (2008). PubMed

Abstract

To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.

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