Geographic Distribution of Chronic Wasting Disease Resistant Alleles in Nebraska, with Comments on the Evolution of Resistance

Infectious diseases create major challenges for wildlife management. In particular, prion diseases are fatal and incurable, leaving managers with limited options. In cervids, chronic wasting disease (CWD) can decimate captive and wild populations by affecting neural tissue leading to body control loss, decay, and ultimately death resulting in ecological and economic consequences. Partial protection against CWD results from some genotypes at the prion (PRNP) locus encoding PrP proteins that are less likely to misfold and build up to fatal levels in the central nervous system. Although multiple studies have documented the association between CWD susceptibility and genotypes, little is known about the distribution of resistant genotypes across the natural landscape, and whether population pockets of protection in exist in particular regions. We surveyed the genetic variability and distribution of resistant alleles and genotypes of the PRNP locus across Nebraska in deer collected in 2017, where mule deer (Odocoileus hemionus) and white-tailed (O. virginianus) deer ranges meet on the North American Great Plains. We found that CWD-resistant alleles occur throughout the state in low frequencies, and our data suggest little evidence of geographic structure for the PRNP locus. In Nebraska, there is a lower frequency of the most common resistance allele (596) compared with white-tailed deer in other parts of the Midwest. The frequency of resistant alleles (F225) was lower in mule deer. The low but widespread frequency of resistance alleles suggests that each species could be susceptible to CWD spread. Continued monitoring would be useful to determine if the frequency of resistant alleles increases in areas with increasing CWD rates. Three synonymous fixed genotypes at the PRNP locus allowed detection of hybrids between mule deer and white-tailed deer, although we found none, suggesting that CWD is not spread between species via hybridization. We also compare the PRNP genotypes of scrapie-resistant sheep with those of deer, and suggest that a single base-pair mutation at the PRNP locus could provide resistance in deer.