Alternative Splicing Signature in human Crohn’s Disease

Abstract

\n Although hundreds of risk loci for Crohn’s disease (CD) have been identified, the underlying pathogenesis of CD remains unclear. Recently, evidence has shown that aberrant gene expression in CD patients’ colon tissues was associated with progression of CD. We reasoned that post-transcriptional regulation, especially alternative splicing (AS), may also play important roles in the pathogenesis of CD. Herein we re-analyzed a public mRNA-seq data from NCBI GEO dataset (GSE66207), and identified approximately 3,000 unique AS events in CD patients compared to the healthy controls. “Lysine degradation” and “Sphingolipid metabolism” are the top two AS events enriched terms in CD patients. In a validation study, we also sequenced 8 subjects and demonstrated that key genes which were previously linked to CDs, such as IRF1, STAT3, also had significant AS events in CDs. In conclusion, our study provided a landscape of AS events in CD, especially as the first study focused on a Chinese cohort. Our data suggested that dysregulation of AS may be a new mechanism that contribute to the pathogenesis of CD.