Accurate Genomic Predictions for Chronic Wasting Disease in U.S. White-Tailed Deer

Seabury, Christopher M.; Oldeschulte, David L.; Bhattarai, Eric K.; Legare, Dhruti; Ferro, Pamela J.; Metz, Richard P.; Johnson, Charles D.; Lockwood, Mitchell A.; Nichols, Tracy A.

doi:10.1534/g3.119.401002

Cited by 20 publications

(44 citation statements)

References 38 publications

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“…We also cannot rule out the potential for linked variation as influencing the observed pattern in Haplotype B, however our results do not find any evidence for increased susceptibility of the variant. Using panels of nuclear markers, we suggest further study of patterns of spatial connectivity and population structure in wild WTD [45] as a means of separating potential spatial and Table 2. PRNP haplotype frequencies and odds-ratios, as associated with CWD status of white-tailed deer in Arkansas, 2016-2019.…”

Section: Discussionmentioning

confidence: 99%

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

Chafin

Douglas

Martin

et al. 2020

Prion

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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 CWDendemic 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, populationlevel characteristic that is detectable through phylogeographic analysis.

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Section: Discussionmentioning

confidence: 99%

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

Chafin

Douglas

Martin

et al. 2020

Prion

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“…The idiosyncratic relationship between PRNP phylogeny and presence of CWD in cervids precludes classification of strains at the level of the gene, and to construct a nomenclature of strains requires specifying the PRNP genotype, the resulting phenotype, and the host in which it was transformed. It is likely that genetic factors other than mutations at PRNP influence susceptibility to CWD ( Seabury et al., 2020 ). Furthermore, there has not been an extensive survey of CWD prion phenotypes throughout wild populations of cervids, and most of the information about ecotypes comes from in vitro experiments with genetically transformed mice.…”

Section: Discussionmentioning

confidence: 99%

“…CWD presence transcends phylogenetic patterns in gene and amino acid trees and suggests causes other than DNA or amino acid sequences ( Mysterud and Edmunds, 2019 ; Zink, 2020 ; Seabury et al., 2020 ). For example, in the 214 white-tailed deer from Nebraska, six genotypes were observed for positions 95, 96, and 116, each with two alleles ( Table 2 ).…”

Section: Exploring Prnp Phylogeny and Cwd In White-tailed Deermentioning

confidence: 99%

Considering the use of the terms strain and adaptation in prion research

Zink

2021

Heliyon

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Evolutionary biologists and disease biologists use the terms strain and adaptation in Chronic Wasting Disease (CWD) research in different ways. In evolutionary biology, a strain is a nascent genetic lineage that can be described by a genealogy, and a phylogenetic nomenclature constructed to reflect that genealogy. Prion strains are described as showing distinct host range, clinical presentation, disease progression, and neuropathological and PrP biochemical profiles, and lack information that would permit phylogenetic reconstruction of their history. Prion strains are alternative protein conformations, sometimes derived from the same genotype. I suggest referring to prion strains as ecotypes, because the variant phenotypic conformations (“strains”) are a function of the interaction between PRNP amino acid genotype and the host environment. In the case of CWD, a prion ecotype in white-tailed deer would be described by its genotype and the host in which it occurs, such as the H95 + ecotype. However, an evolutionary nomenclature is difficult because not all individuals with the same PRNP genotype show signs of CWD, therefore creating a nomenclature reflecting and one-to-one relationship between PRNP genealogy and CWD presence is difficult. Furthermore, very little information exists on the phylogenetic distribution of CWD ecotypes in wild deer populations. Adaptation has a clear meaning in evolutionary biology, the differential survival and reproduction of individual genotypes. If a new prion ecotype arises in a particular host and kills more hosts or kills at an earlier age, it is the antithesis of the evolutionary definition of adaptation. However, prion strains might be transmitted across generations epigenetically, but whether this represents adaptation depends on the fitness consequences of the strain. Protein phenotypes of PRNP that cause transmissible spongiform encephalopathies (TSEs), and CWD, are maladaptive and would not be propagated genetically or epigenetically via a process consistent with an evolutionary view of adaptation. I suggest terming the process of prion strain origination “phenotypic transformation”, and only adaptation if evidence shows they are not maladaptive and persist over evolutionary time periods (e.g., thousands of generations) and across distinct species boundaries (via inheritance). Thus, prion biologists use strain and adaptation, historically evolutionary terms, in quite different ways.

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“…We also cannot rule out the potential for linked variation as influencing the observed pattern in Haplotype B, however our results do not find any evidence for increased susceptibility of the variant. Using panels of nuclear markers, we suggest further study of patterns of spatial connectivity and population structure in wild WTD 46 as a means of separating potential spatial and phylogeographic drivers of haplotype frequencies from those driven by disease-mediated selection.…”

Section: Discussionmentioning

confidence: 99%

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

Chafin

Douglas

Martin

et al. 2020

Preprint

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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 do so as 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.

show abstract

Accurate Genomic Predictions for Chronic Wasting Disease in U.S. White-Tailed Deer

Cited by 20 publications

References 38 publications

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

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

Considering the use of the terms strain and adaptation in prion research

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

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