与自闭症相关的基因——染色质结构域解旋酶DNA结合蛋白8（CHD8）调控非编码RNA和自闭症相关基因。
The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes.
作者信息
Wilkinson B, Grepo N, Thompson B L, Kim J, Wang K, Evgrafov O V, Lu W, Knowles J A, Campbell D B
机构信息
Development, Stem Cells, and Regeneration Ph.D. Program, University of Southern California, Los Angeles, CA, USA.
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
出版信息
Transl Psychiatry. 2015 May 19;5(5):e568. doi: 10.1038/tp.2015.62.
Chromodomain helicase DNA-binding protein 8 (CHD8) was identified as a leading autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and subsequent targeted-sequencing studies. De novo loss-of-function mutations were identified in 12 individuals with ASD and zero controls, accounting for a highly significant association. Small interfering RNA-mediated knockdown of CHD8 in human neural progenitor cells followed by RNA sequencing revealed that CHD8 insufficiency results in altered expression of 1715 genes, including both protein-coding and noncoding RNAs. Among the 10 most changed transcripts, 4 (40%) were noncoding RNAs. The transcriptional changes among protein-coding genes involved a highly interconnected network of genes that are enriched in neuronal development and in previously identified ASD candidate genes. These results suggest that CHD8 insufficiency may be a central hub in neuronal development and ASD risk.
通过全外显子组测序及后续靶向测序研究，染色质结构域解旋酶DNA结合蛋白8（CHD8）被确定为孤独症谱系障碍（ASD）的主要候选基因。在12例ASD患者中发现了新生功能丧失性突变，而在对照中未发现，这一结果具有高度显著的关联性。在人类神经祖细胞中通过小干扰RNA介导敲低CHD8，随后进行RNA测序，结果显示CHD8功能不足导致1715个基因的表达发生改变，包括蛋白质编码RNA和非编码RNA。在变化最大的10个转录本中，有4个（40%）是非编码RNA。蛋白质编码基因中的转录变化涉及一个高度互联的基因网络，这些基因在神经元发育和先前确定的ASD候选基因中富集。这些结果表明，CHD8功能不足可能是神经元发育和ASD风险的核心枢纽。
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