The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes

被引：0
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作者：
B Wilkinson
N Grepo
B L Thompson
J Kim
K Wang
O V Evgrafov
W Lu
J A Knowles
D B Campbell
机构：
[1] Development,Division of Occupational Science and Occupational Therapy
[2] Stem Cells,Department of Psychiatry and the Behavioral Sciences
[3] and Regeneration Ph.D. Program,Department of Biochemistry and Molecular Biology
[4] University of Southern California,undefined
[5] Zilkha Neurogenetic Institute,undefined
[6] Keck School of Medicine,undefined
[7] University of Southern California,undefined
[8] Herman Ostrow School of Dentistry,undefined
[9] University of Southern California,undefined
[10] Keck School of Medicine,undefined
[11] University of Southern California,undefined
[12] Broad Center for Regenerative Medicine and Stem Cell Research,undefined
[13] Keck School of Medicine,undefined
[14] University of Southern California,undefined
[15] Keck School of Medicine,undefined
[16] University of Southern California,undefined
来源：
Translational Psychiatry | 2015年 / 5卷
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摘要：
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.
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页码：e568 / e568
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