Age structuring and spatial heterogeneity in prion protein gene (PRNP) polymorphism in white-tailed deer

Prion. 2020 Dec;14(1):238-248. doi: 10.1080/19336896.2020.1832947.

Abstract

Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications of PRNP polymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) of PRNP variants in hunter-harvested white-tailed deer (WTD; Odocoileus virginianus, N = 1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these, PRNP variants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWD-endemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly reflect an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of 'reduced susceptibility' genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, population-level characteristic that is detectable through phylogeographic analysis.

Keywords: Adaptive management; chronic-wasting disease; demography; disease susceptibility; haplotype; selection; white-tailed deer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / genetics*
  • Aging / pathology*
  • Animals
  • Deer / genetics*
  • Female
  • Gene Frequency / genetics
  • Geography
  • Haplotypes / genetics
  • Odds Ratio
  • Polymorphism, Genetic*
  • Prion Proteins / genetics*

Substances

  • Prion Proteins

Grants and funding

This project and the preparation of this publication were funded in part by the Pittman-Robertson Wildlife Restoration Grant Program (Grant #AR-W-F18AF00020) of the U.S. Fish and Wildlife Service through an agreement with the Arkansas Game and Fish Commission. The views and opinions expressed herein are those of the authors and do not necessarily reflect the views or policies of the Arkansas Game and Fish Commission. Product references do not constitute endorsements;XSEDE [TG-BIO160065];U.S. Fish and Wildlife Service [AR-W-F18AF00020];