Improving application of human leukocyte antigen genotyping in precision medicine

Abstract

Variation in the human leukocyte antigen (HLA) genes has been extensively associated with predisposition to autoimmune disease and adverse drug reaction. Translation of these associations to clinical practice has proven to be difficult due to the high cost and time burden of genetic testing. Additionally, understanding the value of prospective HLA associations in a research context is challenging due to the unparalleled polymorphisms of the HLA genes, as well as interactions between HLA variants. In this thesis, tools and methods are described which assist in the interpretation of prospective HLA associations and definition of the clinical role of HLA genotyping. Importantly, techniques that improve the efficiency of genetic testing of HLA variants are also reported.