Abstract
Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy (TSE) of cervids caused by a misfolded variant of the normal cellular prion protein, and it is closely related to sheep scrapie. Variations in a host’s prion gene, PRNP, and its primary protein structure dramatically affect susceptibility to specific prion disorders, and breeding for PRNP variants that prevent scrapie infection has led to steep declines in the disease in North American and European sheep. While resistant alleles have been identified in cervids, a PRNP variant that completely prevents CWD has not yet been identified. Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. In CWD-endemic areas, depopulation of private herds becomes challenging to justify, leading to opportunities to manage the disease in situ. We developed a selective breeding program for farmed white-tailed deer in a high-prevalence CWD-endemic area which focused on reducing frequencies of highly susceptible PRNP variants and introducing animals with less susceptible variants. With the use of newly developed primers, we found that breeding followed predictable Mendelian inheritance, and early data support our project’s utility in reducing CWD prevalence. This project represents a novel approach to CWD management, with future efforts building on these findings.
Highlights
Chronic wasting disease (CWD) is a progressive and fatal transmissible spongiform encephalopathy (TSE) affecting both farmed and free-ranging populations of deer, elk, and other cervid species [1,2,3]
The causative agent of TSEs, a disease category that includes sheep scrapie, bovine spongiform encephalopathy, and human kuru and Creutzfeldt–Jakob disease, is a misfolded, protease-resistant prion protein often denoted PrPres [7,8]. This misfolded prion protein is a conformer of a normal cellular prion protein, PrPC, a ~250 amino acid protein encoded by a single-copy gene (PRNP) that has been reported in a broad range of mammalian, avian, reptilian, amphibian, and piscine species [8,9]
Dozens if not hundreds of PRNP alleles have been reported in sheep, for example, and prevalence studies have identified variants with polymorphisms at positions 136, 154, and 171 of the ovine prion gene that are associated with high levels of resistance to sheep scrapie [20]
Summary
Chronic wasting disease (CWD) is a progressive and fatal transmissible spongiform encephalopathy (TSE) affecting both farmed and free-ranging populations of deer, elk, and other cervid species [1,2,3]. The goals of our study were to (1) determine the PRNP genotypes of breeding animals and work hand in hand with the farm owner to develop a breeding program to reduce the frequency of highly susceptible PRNP genotypes, (2) evaluate PRNP genotypes and associated CWD prevalence on the two CWD-positive hunting preserves prior to our planned interventions, and (3) assess the preliminarily effectiveness of selective breeding on reducing CWD prevalence on these two sites, while preventing the incursion of CWD on the remaining properties. We hypothesized that genetic shifts toward animals with reduced susceptibility to CWD would result in lower disease prevalence on both CWD-positive hunting preserves In this first phase of a three-phase study, we found high frequencies of 96G variants (where variant frequency is defined as the percentage of a specific haplotype or variant, in this case 96G, among all chromosomes in the population) and 96GG homozygous genotypes (91% and 83%, respectively) on the breeding farms. We plan to continue selective breeding into future years, eliminating the 96G variant from the herd, while continuously monitoring disease prevalence and other metrics on all properties
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