Title:
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An investigation into the molecular genetics of the inflammatory bowel diseases
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The aims of this thesis were firstly to investigate gene expression profiles in human colonic and terminal ileal biopsies using microarray technology in a well phenotyped cohort of patients with Crohn's disease, ulcerative colitis and a control cohort. The role in disease pathogenesis of differentially expressed genes was investigated along with the expression of candidate genes identified by genome wide association study and cell lineage analysis. Parallel studies attempted to replicate the Nature Genetics publications of Peltekova and Stoll and colleagues who investigated the role the IBD5 locus and the DLG5 gene respectively in patients with inflammatory bowel disease. Overall these data emphasise the key role of a number of inflammatory molecules and pathways in pathogenesis of Crohn's disease and ulcerative colitis, and their potential for translation to therapeutic targets. The results also add considerably to the recent genome wide association studies in providing complimentary human colonic and ileal expression data along with detailed analysis of the IL-23 and autophagy pathways.
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