Co-expression of long non-coding RNAs and autism risk genes in the developing human brain

Steven B Cogill,Mary Qu Yang,Anand K Srivastava,Liangjiang Wang

doi:10.1186/s12918-018-0639-x

Steven B Cogill, Mary Qu Yang + Show 2 more

Open Access

https://doi.org/10.1186/s12918-018-0639-x

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Abstract

BackgroundAutism Spectrum Disorder (ASD) is the umbrella term for a group of neurodevelopmental disorders convergent on behavioral phenotypes. While many genes have been implicated in the disorder, the predominant focus of previous research has been on protein coding genes. This leaves a vast number of long non-coding RNAs (lncRNAs) not characterized for their role in the disorder although lncRNAs have been shown to play important roles in development and are highly represented in the brain. Studies have also shown lncRNAs to be differentially expressed in ASD affected brains. However, there has yet to be an enrichment analysis of the shared ontologies and pathways of known ASD genes and lncRNAs in normal brain development.ResultsIn this study, we performed co-expression network analysis on the developing brain transcriptome to identify potential lncRNAs associated with ASD and possible annotations for functional role of lncRNAs in brain development. We found co-enrichment of lncRNA genes and ASD risk genes in two distinct groups of modules showing elevated prenatal and postnatal expression patterns, respectively. Further enrichment analysis of the module groups indicated that the early expression modules were comprised mainly of transcriptional regulators while the later expression modules were associated with synapse formation. Finally, lncRNAs were prioritized for their connectivity with the known ASD risk genes through analysis of an adjacency matrix. Collectively, the results imply early developmental repression of synaptic genes through lncRNAs and ASD transcriptional regulators.ConclusionHere we demonstrate the utility of mining the publically available brain gene expression data to further functionally annotate the role of lncRNAs in ASD. Our analysis indicates that lncRNAs potentially have a key role in ASD due to their convergence on shared pathways, and we identify lncRNAs of interest that may lead to further avenues of study.

Highlights

Autism Spectrum Disorder (ASD) is the umbrella term for a group of neurodevelopmental disorders convergent on behavioral phenotypes
While protein-coding genes account for only 40.4% of the genes within the original dataset, after curation they account for 71.1% while antisense long non-coding RNA (lncRNA) genes and long intervening RNA genes originally comprised 19.1% of the dataset were reduced down to 11%
In this study, we performed gene co-expression network analysis to identify candidate lncRNAs associated with ASD

Summary

Introduction

Autism Spectrum Disorder (ASD) is the umbrella term for a group of neurodevelopmental disorders convergent on behavioral phenotypes. While many genes have been implicated in the disorder, the predominant focus of previous research has been on protein coding genes This leaves a vast number of long non-coding RNAs (lncRNAs) not characterized for their role in the disorder lncRNAs have been shown to play important roles in development and are highly represented in the brain. Long non-coding RNAs (lncRNAs) are defined as transcripts greater than 200 nucleotides in length, which do not code for proteins. They serve a wide range of functions including, but not limited to, scaffolding for protein complexes, transcriptional regulation, and translational regulation [1,2,3]. ASD risk genes are convergent on synaptic gene translation, transcription and chromatin remodeling [11, 13], and these three processes can be controlled by lncRNAs [14]

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