title: The autism-associated gene chromodomain helicase DNA-binding protein 8 (CHD8) regulates noncoding RNAs and autism-related genes.
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.
authors.affiliation: Development, Stem Cells, and Regeneration Ph.D. Program, University of Southern California, Los Angeles, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Wilkinson
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Grepo
authors.affiliation: Division of Occupational Science and Occupational Therapy, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Thompson
authors.affiliation: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.affiliation: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: O V
authors.initials: OV
authors.lastname: Evgrafov
authors.affiliation: 1] Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.affiliation: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.affiliation: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Campbell
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C523331:CHD8 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D014157:Transcription Factors