Genome-wide profiling of differentially spliced mRNAs in human fetal cortical tissue exposed to alcohol

Abstract

Excessive alcohol consumption results in significant changes in gene expression and isoforms due to altered mRNA splicing. As such, an intriguing possibility is that disturbances in alternative splicing are involved in key pathological pathways triggered by alcohol exposure. However, no resources have been available to systematically analyze this possibility at a genome-wide scale. Here, we performed RNA sequencing of human fetal cortical slices that were obtained at the late first trimester and exposed to ethanol or control medium. We report 382 events that were identified as changes affecting the ratio of splicing isoforms in the ethanol-exposed fetal human cortex. Additionally, previously unreported novel isoforms of several genes were also identified. These results provide a broad perspective on the post-transcriptional regulatory network underlying ethanol-induced pathogenesis in the developing human cortex.

Keywords: Alternative splicing; Human fetal cerebral cortex; Prenatal alcohol exposure; RNA sequencing.