Selective Breeding for Disease-Resistant PRNP Variants to Manage Chronic Wasting Disease in Farmed Whitetail Deer

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.

Detection of Chronic Wasting Disease Prions in Fetal Tissues of Free-Ranging White-Tailed Deer

“…Prnp polymorphisms have been shown to play a role in both scrapie and CWD susceptibility [44][45][46]. The white-tailed deer fetuses in this study were all codon 96 GG, and thus from current understanding, carry a genotype that supports CWD infection.…”

Transmission, Strain Diversity, and Zoonotic Potential of Chronic Wasting Disease

“…Thus, one strategy to minimize CWD spreading might be to perform selective breeding to produce animals with several polymorphic variants known to decrease infection. A recent study has shown that selective breeding might contribute to reduce CWD spreading [ 109 ]. A similar strategy was previously employed to attempt reducing prevalence of scrapie in sheep [ 110 ].…”

County-wide assessments of Illinois white-tailed deer (Odocoileus virginianus) prion protein gene variation using improved primers and potential implications for management

“…In the case of sequencing PRNP in white-tailed deer, evidence of allelic dropout has recently been reported using one of the more commonly used primer sets. Researchers identified a polymorphism in the forward primer binding site [ 14 ] that prevents primer annealing leading to allelic dropout [ 27 ]. Ultimately, this leads to incorrect PRNP genotyping for deer carrying the primer binding site polymorphism [ 27 ].…”

“…Researchers identified a polymorphism in the forward primer binding site [ 14 ] that prevents primer annealing leading to allelic dropout [ 27 ]. Ultimately, this leads to incorrect PRNP genotyping for deer carrying the primer binding site polymorphism [ 27 ]. Therefore, it is important to determine the extent of this polymorphism in the Illinois wild white-tailed deer population in order to determine its effect on the accuracy of previous Illinois PRNP published frequencies.…”

“…Diplotype is defined as the two haplotypes within each individual diploid deer, and PrP proteotype is defined as the two proteoforms encoded by each haplotype within each individual. We evaluated the PRNP allelic frequencies obtained using primers by [ 14 ] (O’Rourke primers) and by [ 27 ] (Haley primers) and compared the proportion of PrP homozygous (individuals with two copies of same PRNP haplotypes) and heterozygous (individuals with two different PRNP haplotypes) using both sets of primers. Overall, by examining the composition and distribution, frequencies, and temporal changes in the genetic vulnerability of deer populations within these counties we sought to provide information for managers seeking to contain CWD within the state of Illinois.…”