Abstract
BackgroundAlthough numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear. Recently, multiple transcriptomic analyses have shown that aberrant gene expression in the colon tissues of UC patients is associated with disease progression. A pioneering study also demonstrated that altered post-transcriptional regulation is involved in the progression of UC. Here, we provide a genome-wide analysis of alternative splicing (AS) signatures in UC patients. We analyzed three datasets containing 74 tissue samples from UC patients and identified over 2000 significant AS events.ResultsSkipped exon and alternative first exon were the two most significantly altered AS events in UC patients. The immune response-related pathways were remarkably enriched in the UC-related AS events. Genes with significant AS events were more likely to be dysregulated at the expression level.ConclusionsWe present a genomic landscape of AS events in UC patients based on a combined analysis of two cohorts. Our results indicate that dysregulation of AS may have a pivotal role in determining the pathogenesis of UC. In addition, our study uncovers genes with potential therapeutic implications for UC treatment.
Highlights
Numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear
Types of alternative splicing in the GSE137344 public dataset Eight types of AS events were discovered in UC samples from the GSE137344 public dataset: alternative 3’splice site, alternative 5’splice site, alternative first exon (AFE), alternative last exon (ALE), mutually exclusive exons (MXE), retrained introns (RI), skipped exon (SE), and tandem 3′ UTR (Fig. 1A)
Most belonged to the SE type, but the total number of SE events was relatively low versus other events (Fig. 1B)
Summary
Numerous risk loci for ulcerative colitis (UC) have been identified in the human genome, the pathogenesis of UC remains unclear. Multiple transcriptomic analyses have shown that aberrant gene expression in the colon tissues of UC patients is associated with disease progression. A pioneering study demonstrated that altered post-transcriptional regulation is involved in the progression of UC. We analyzed three datasets containing 74 tissue samples from UC patients and identified over 2000 significant AS events. Multiple genome-wide association studies have identified hundreds of associated genetic risk loci in patients with UC [4], its pathogenesis remains unclear. Several transcriptomic studies have been performed to determine gene expression alterations in patients with different subtypes of IBD. Planell et al analyzed colonic biopsies from patients with active or inactive UC and healthy controls using microarrays.
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