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Evidence for enhancer noncoding RNAs (enhancer-ncRNAs) with gene regulatory functions relevant to neurodevelopmental disorders

Asgari, Y.; Heng, J. I.-T.; Lovell, N.; Forrest, A.; Alinejad-Rokny, H.

2020-11-05 neuroscience
10.1101/2020.05.16.087395 bioRxiv
Show abstract

Noncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment disorders is poorly understood. In this study, we identified 908 brain-enriched noncoding RNAs comprising at least one nervous system-related eQTL polymorphism that is associated with protein coding genes and also overlap with chromatin states characterised as enhancers. We referred to such noncoding RNAs with putative enhancer activity as brain enhancer-ncRNAs. By integrating GWAS SNPs and Copy Number Variation (CNV) data from neurodevelopment disorders, we found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTL-associated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. Taken together, we identified 49 novel NDD-associated ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders.

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