Characterization of single-nucleotide polymorphisms implicated in the pathogenesis of Crohn's disease

The inflammatory bowel diseases (IBD) are a group of chronic inflammatory conditions involving the gastrointestinal tract. IBD affects between 1 and 2 million Americans, and its incidence is increasing for unknown reasons. One of the predominant forms of IBD is Crohn’s disease (CD). Genome-wide association studies (GWAS) have linked many single-nucleotide polymorphisms (SNPs) within genes of the immune system to CD pathogenesis, but it is unknown which of these SNPs are causative. In genetically susceptible individuals, CD can result from a disruption in the balance between pro-inflammatory and anti-inflammatory gene expression in intestinal immune cells. Gene expression is partially regulated by the binding of transcription factors to DNA to either activate or repress target genes. The ability of transcription factors to bind to DNA may be influenced by chromatin accessibility. To determine the location of accessible, or “open” chromatin regions in the genome, we used Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE). Many of these open chromatin regions were located near genes involved in immune system function. A subset of these open chromatin regions overlapped with CD-associated SNPs. I used luciferase reporter assays to determine the potential regulatory function of a CD-linked SNP found in a region of open chromatin. Understanding the function of disease-associated genetic variants will elucidate the importance of genetic susceptibility in CD pathogenesis.Bachelor of Scienc