The Autism-associated Gene Chromodomain Helicase DNA-binding Protein 8 (CHD8) Regulates Noncoding RNAs and Autism-related Genes

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2015 May 20

PMID 25989142

Citations 65

Authors

B Wilkinson

N Grepo

B L Thompson

J Kim

K Wang

O V Evgrafov

W Lu

J A Knowles

D B Campbell

Affiliations

Soon will be listed here.

Abstract

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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