TY - JOUR
T1 - Identifying autism loci and genes by tracing recent shared ancestry
AU - Morrow, Eric M.
AU - Yoo, Seung Yun
AU - Flavell, Steven W.
AU - Kim, Tae Kyung
AU - Lin, Yingxi
AU - Hill, Robert Sean
AU - Mukaddes, Nahit M.
AU - Balkhy, Soher
AU - Gascon, Generoso
AU - Hashmi, Asif
AU - Al-Saad, Samira
AU - Ware, Janice
AU - Joseph, Robert M.
AU - Greenblatt, Rachel
AU - Gleason, Danielle
AU - Ertelt, Julia A.
AU - Apse, Kira A.
AU - Bodell, Adria
AU - Partlow, Jennifer N.
AU - Barry, Brenda
AU - Yao, Hui
AU - Markianos, Kyriacos
AU - Ferland, Russell J.
AU - Greenberg, Michael E.
AU - Walsh, Christopher A.
PY - 2008/7/11
Y1 - 2008/7/11
N2 - 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.
AB - 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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U2 - 10.1126/science.1157657
DO - 10.1126/science.1157657
M3 - Article
C2 - 18621663
AN - SCOPUS:47249088331
SN - 0036-8075
VL - 321
SP - 218
EP - 223
JO - Science
JF - Science
IS - 5886
ER -