Chronic wasting disease associated with prion protein gene (PRNP) variation in Norwegian wild reindeer (Rangifer tarandus)

Mariella E Güere,Jørn Våge,Helene Tharaldsen,Sylvie L Benestad,Turid Vikøren,Knut Madslien,Petter Hopp,Christer M Rolandsen,Knut H Røed,Michael A Tranulis

doi:10.1080/19336896.2019.1702446

Abstract

ABSTRACT The emergence of CWD in Europe in 2016 and the first natural infection in wild reindeer warranted disease management. This led to the testing of 2424 hunted or culled reindeer during 2016–2018, from the infected subpopulation in the Nordfjella mountain range in Southern Norway. To identify any association between PRNP variation and CWD susceptibility, we characterized the open reading frame of the PRNP gene in 19 CWD positive reindeer and in 101 age category- and sex-matched CWD negative controls. Seven variant positions were identified: 6 single nucleotide variants (SNVs) and a 24 base pair (bp) deletion located between nucleotide position 238 and 272, encoding four instead of five octapeptide repeats. With a single exception, all variant positions but one were predicted to be non-synonymous. The synonymous SNV and the deletion are novel in reindeer. Various combinations of the non-synonymous variant positions resulted in the identification of five PRNP alleles (A-E) that structured into 14 genotypes. We identified an increased CWD risk in reindeer carrying two copies of the most common allele, A, coding for serine in position 225 (Ser225) and in those carrying allele A together with the 24 bp deletion.

Highlights

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting ruminants of the Cervidae family [1], like Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in small ruminants
All variant positions were in Hardy– Weinberg Equilibrium (HWE) (P-value = 0.603–1.000)
The model revealed that carrying two copies of allele A (Ser225) and/or allele C is a risk factor for CWD, significantly increasing the odds ratio (O.R.) (O.R: 42.39; 95% C.I. = 5.12–5534.03) (Table 2). This is the first study to analyse PRNP coding variation among cases and controls in a population of wild reindeer sampled during an outbreak of CWD

Summary

Introduction

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting ruminants of the Cervidae family [1], like Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in small ruminants. CWD expanded its geographic distribution and possibly its prion strain diversity with the emergence in Eurasian reindeer (Rangifer tarandus) [2] and moose [3] in Norway in 2016. This disease had been confined to North America and the Republic of Korea, reported for the first time in Colorado, USA in 1967. There is a single report of CWD detection in wild-red deer (Cervus elaphus) in Europe [5], even though former reports in captive herds [6,7]

Methods

Results

Conclusion