| Summary: | The etiological agents’ nature has a pivotal role in the pathogenesis of infectious diseases. Prion diseases are unique in having a misfolded protein (PrPSc) as the sole transmissible agent. The host cellular protein (PrPC) is the substrate for misfolding and aggregation by PrPSc. Variability in the prion protein gene (PRNP) encoding PrPC affects prion disease progression and susceptibility, probably by inducing changes that may alter the efficiency of a pathogenic PrPC-to-PrPSc conversion. This principle applies to Chronic Wasting Disease (CWD; MONDO_0002680), a prion disease affecting members of the family Cervidae. CWD is widely distributed in North America from where it was imported to the Republic of Korea. Identification of CWD in Norway in wild reindeer (Rangifer tarandus) in 2016 and its subsequent identification in moose (Alces alces), and red deer (Cervus elaphus) has raised questions regarding the apparent geographical expansion of this disease in Europe. One key question targets the variation in the host PRNP, an important genetic risk factor in prion disease. This thesis studies PRNP variability in Norwegian cervids, where most European cases have been identified to June 2021. The endemic Norwegian species are reindeer, red deer, moose, and roe deer (Capreolus capreolus) with reindeer managed between, semi-domestic- or wild- populations. The first cases of CWD in Europe were recorded among the Norwegian wild reindeer population in Nordfjella 1, part of the Nordfjella management area in Southern Norway, where 19 CWD cases were identified. In this population, the risk to test positive to CWD was found to be greater in adult males and this likelihood increased with age. Similarly, two PRNP genotypes were found to increase the risk of CWD development in these wild reindeer. These susceptible genotypes combine two variants of PRNP (called alleles) named 226Q and deletion_226Q. Aware of the implications further spread of CWD could have for European cervid populations, a collaboration between scientists ...
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