Genetics of Autism
Genetics of Autism
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DOI：
10.1007/978-3-540-37654-5_23.4
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Geschwind, Daniel H.
中科院分区：
文献类型：
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作者：
Abrahams, Brett S.;Geschwind, Daniel H.
过去 3 年，我们对自闭症分子遗传学的了解比过去 30 年还要多。这包括对罕见遗传变异作用的新认识，以及通过全基因组关联识别第一个有贡献的常见变异。这些数据表明，虽然共同变异的人群归因风险可能为中等到大，但个体水平上常见变异的基因型风险很小。相比之下，已经鉴定出大量具有重大影响的不同罕见突变，但没有一个突变是自闭症特有的。所有这些发现都表明极端的遗传异质性表明自闭症病因学中存在复杂的基因-基因或基因-环境相互作用。下面回顾的现有知识还表明，表型表现是复杂相互作用的结果，并且在许多情况下涉及的遗传风险因素跨越了已建立的临床诊断类别的界限。接受这种复杂性并努力理解中间表型方面的遗传变异代表了未来研究的重要方向。
We have learned more about the molecular genetics of autism in the last 3 years than in the previous 30. This includes both a new appreciation for the role of rare genetic variation and the identification of the first contributory common variants by genome-wide association. These data show that although the population attributable risk of common variation may be moderate to large, the genotype risk of common variants at the individual level are small. In contrast, a large number of diverse rare Mutations of large effect have been identified, but none appear specific to autism. All of these findings point to extreme genetic heterogeneity suggesting complex gene-gene or gene-environment interactions in autism etiology. Available knowledge, reviewed below, also suggests that phenotypic presentation is the result of complex interactions, and that implicated genetic risk factors in many cases cross the boundaries of established clinical diagnostic categories. Acceptance of this complexity and efforts to understand genetic variation in terms of intermediate phenotypes represent important directions for future research.