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

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, accounti...

Descripción completa

Detalles Bibliográficos
Autores principales: Wilkinson, B, Grepo, N, Thompson, B L, Kim, J, Wang, K, Evgrafov, O V, Lu, W, Knowles, J A, Campbell, D B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471293/
https://www.ncbi.nlm.nih.gov/pubmed/25989142
http://dx.doi.org/10.1038/tp.2015.62
Descripción
Sumario: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.

Ejemplares similares