Autism spectrum disorders: from genes to neurobiology.
Autism spectrum disorders: from genes to neurobiology.
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DOI：
10.1016/j.conb.2014.10.015
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发表时间：
2015-02
影响因子：
5.7
通讯作者：
State MW
中科院分区：
文献类型：
--
作者：
Willsey AJ;State MW
全基因组技术的进步，加上大群体的可用性，最终产生了稳定的自闭症谱系障碍（ASD）基因携带突变的大影响。这些发现代表了重要的分子线索，但同时也对从基因到神经生物学的传统策略提出了显著的挑战。遗传异质性的显著程度，ASD基因的生物多效性，以及人类大脑的巨大复杂性，都促使人们开发新的方法，将遗传发现转化为治疗靶点。系统生物学方法的最新发展，“情境化”这些遗传研究结果沿着空间，时间和细胞轴的人脑发育开始弥合高通量基因发现和可测试的病理生理学假说之间的差距。
Advances in genome-wide technology, coupled with the availability of large cohorts, are finally yielding a steady stream of autism spectrum disorder (ASD) genes carrying mutations of large effect. These findings represent important molecular clues, but at the same time present notable challenges to traditional strategies for moving from genes to neurobiology. A remarkable degree of genetic heterogeneity, the biological pleiotropy of ASD genes, and the tremendous complexity of the human brain are prompting the development of new approaches to translating genetic discoveries into therapeutic targets. Recent developments in systems biology approaches that ‘contextualize’ these genetic findings along spatial, temporal, and cellular axes of human brain development are beginning to bridge the gap between high-throughput gene discovery and testable pathophysiological hypotheses.