The genetics of autism: key issues, recent findings, and clinical implications.
The genetics of autism: key issues, recent findings, and clinical implications.
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DOI：
10.1016/j.psc.2009.12.002
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
State MW
中科院分区：
文献类型：
--
作者：
El-Fishawy P;State MW
自闭症谱系障碍（ASD'S）是高度遗传的。因此，基因发现有望帮助阐明这些综合征的病理生理学，为开发新的治疗方法和更细致地了解这些疾病的自然史提供重要机会。虽然ASD的潜在遗传结构尚不清楚，但文献表明，它不是具有孟德尔遗传的单基因疾病，而是一组复杂的遗传综合征，其风险来自多个基因的遗传变异。被广泛接受的“常见病-常见变异”假说预测，ASD和其他复杂疾病中的风险等位基因在普通人群中是常见的。然而，最近的证据，从基因发现的努力，在广泛的疾病提出了重要的问题，在整体上的适用性的理论和它的有用程度，在解释个人的遗传责任。相比之下，大量证据表明，罕见等位基因的重要性，无论是在他们的价值提供一个立足点到ASD的分子机制和他们的整体贡献的人群范围内的风险。本章回顾了常见与罕见变异辩论的起源，强调了该领域的最新研究结果，并讨论了常见和罕见变异发现的临床意义。
Autism spectrum disorders (ASD’S) are highly heritable. Consequently, gene discovery promises to help illuminate the pathophysiology of these syndromes, yielding important opportunities for the development of novel treatments and a more nuanced understanding of the natural history of these disorders. Although the underlying genetic architecture of ASD’s is not yet known, the literature demonstrates that it is not, writ large, a monogenic disorder with Mendelian inheritance, but rather a group of complex genetic syndromes with risk deriving from genetic variations in multiple genes. The widely accepted “Common Disease-Common Variant” hypothesis predicts that the risk alleles in ASD’s and other complex disorders will be common in the general population. However, recent evidence from gene discovery efforts in a wide range of diseases raises important questions regarding the overall applicability of the theory and the extent of its usefulness in explaining individual genetic liability. In contrast, considerable evidence points to the importance of rare alleles both with regard to their value in providing a foothold into the molecular mechanisms of ASD and their overall contribution to the population-wide risk. This chapter reviews the origins of the common versus rare variant debate, highlights recent findings in the field, and addresses the clinical implications of both common and rare variant discoveries.