Identifying autism loci and genes by tracing recent shared ancestry

Science. 2008 Jul 11;321(5886):218-23. doi: 10.1126/science.1157657.

Eric M Morrow ¹, Seung-Yun Yoo, Steven W Flavell, Tae-Kyung Kim, Yingxi Lin, Robert Sean Hill, Nahit M Mukaddes, Soher Balkhy, Generoso Gascon, Asif Hashmi, Samira Al-Saad, Janice Ware, Robert M Joseph, Rachel Greenblatt, Danielle Gleason, Julia A Ertelt, Kira A Apse, Adria Bodell, Jennifer N Partlow, Brenda Barry, Hui Yao, Kyriacos Markianos, Russell J Ferland, Michael E Greenberg, Christopher A Walsh

Affiliations

Affiliation

1 Division of Genetics, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.

PMID: 18621663 DOI: 10.1126/science.1157657

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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