Bioinformatic analysis of the Human Leucocyte Antigen in Inflammatory BowelDisease

The Human Leucocyte Antigen (HLA) has been identified as a genetic risk factor for Inflammatory Bowel Diseases (IBD). The causative role of the HLA in IBD remains to be revealed.

The aim of this thesis is to gain as much understanding as possible about the HLA alleles genetically associated with Ulcerative Colitis (UC), a subtype of IBD.

This cumulative thesis includes two papers published in peer-reviewed journals and an additional manuscript which is in progress. In the first publication, presented in this thesis (Section 6.3), we built an imputation panel that enabled the analysis of IBD and the associated HLA alleles and their corresponding haplotypes across different ancestries. In the second publication (Section 7.3), I analyzed the interaction of peptides with a defined set of HLA alleles associated with UC. This study was the first to use ultra-high density microarray data for predicting the binding status of HLA alleles and peptides. In the final manuscript (Section 8.3), I studied the genetics of UC in Caucasian individuals. I analyzed, what the genetics, combined with prior knowledge about different genes and their protein function, can tell us about a hypothesized peptide that might be a key player in the pathogenesis of UC. Next to some improvements in the imputation of HLA genomes and the binding prediction, this thesis points out first concrete candidate peptides and suggests a path to continue to discover more about the contribution of the HLA in UC.

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