Identifying autism loci and genes by tracing recent shared ancestry.
Identifying autism loci and genes by tracing recent shared ancestry.
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DOI：
10.1126/science.1157657
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发表时间：
2008-07-11
期刊：
影响因子：
56.9
通讯作者：
Walsh, Christopher A.
中科院分区：
文献类型：
--
作者：
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.
为了找到自闭症谱系障碍的遗传原因，我们研究了父母有共同祖先的家庭，增强了遗传因素的作用。我们绘制了几个基因座，其中一些含有大的、遗传的、纯合的缺失，这些缺失很可能是突变。最大的缺失涉及基因，包括PCDH10（原钙粘蛋白10）和DIA1（在自闭症中缺失，或c3orf58），其表达水平随神经元活动而变化，神经元活动是参与学习基础突触变化的基因标志。包括NHE9 （Na+/H+交换器9）在内的基因子集在父母无亲缘关系的患者中显示出额外的潜在突变。我们的发现强调了“纯合子定位”在自闭症等异质性疾病中的效用，但也表明，神经活动后基因表达的缺陷调节可能是一种看似多样的自闭症突变的共同机制。
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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