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Imputation HLA et analyse génomique de la coinfection VIH/VHC

Abstract : Association genomics aims at finding links between the genome and some traits or illnesses. Today, the most frequent studies in this field are genome wide association studies (GWAS), which analyze as many genome variants (mainly Single Nucleotide Polymorphisms) as possible, without any a priori on their biological function. However, genotyping methods used in these studies may be insufficient to get reliable information in higly variable regions such as the HLA which plays a crucial role in immunity, and the genetic variants of such regions are often predicted using bioinformatics approaches. During my PhD, I have created a new tool, HLA-Check, that allows to rate the plausibility of HLA alleles from the genotypes obtained from genotyping chips. I also assesses its performances and showed that it was able to point out individuals with a wrong HLA typing, in order to retype them or remove them from the study. An article documenting this tool was published in BMC Bioinformatics. I have also performed a genome-wide association study on cirrhosis outbreak in individuals coinfected with HIV (human immunodeficiency virus) and HCV (hepatitis C virus). Because of similar infection routes (blood-related), co-infection with those two viruses are frequent, and the infection by HIV enhances HCV activity and increases liver fibrosis leading to cirrhosis and death of co-infected patients. Our study has dealt with 306 co-infected patients from the ANRS CO-13 HEPAVIH cohort. I could point out three statistically significant signals, two of them being highly relevant for their involvement in liver diseases (gene CTNND2 and gene MIR7-3HG). The identification of these new variants should lead to a better understanding of the molecular mechanisms involved in cirrhosis, and should contribute to the rational developement of new diagnostic or therapeutic strategies. A publication is under way.
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Submitted on : Tuesday, September 4, 2018 - 3:52:10 PM
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Marc Jeanmougin. Imputation HLA et analyse génomique de la coinfection VIH/VHC. Médecine humaine et pathologie. Conservatoire national des arts et metiers - CNAM, 2017. Français. ⟨NNT : 2017CNAM1164⟩. ⟨tel-01867773⟩

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