Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry

• DOI: 10.1126/science.1157657
• Publication Date: 2008-07-10T20:47:15Z
• Authors: Eric M. Morrow; 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
• Keywords: Protocadherin; Disease gene identification

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