Dataset Information

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

ABSTRACT: The geographic expansion of chronic wasting disease (CWD) in U.S. white-tailed deer (Odocoileus virginianus) has been largely unabated by best management practices, diagnostic surveillance, and depopulation of positive herds. Using a custom Affymetrix Axiom single nucleotide polymorphism (SNP) array, we demonstrate that both differential susceptibility to CWD, and natural variation in disease progression, are moderately to highly heritable ([Formula: see text] among farmed U.S. white-tailed deer, and that loci other than PRNP are involved. Genome-wide association analyses using 123,987 quality filtered SNPs for a geographically diverse cohort of 807 farmed U.S. white-tailed deer (n = 284 CWD positive; n = 523 CWD non-detect) confirmed the prion gene (PRNP; G96S) as a large-effect risk locus (P-value < 6.3E-11), as evidenced by the estimated proportion of phenotypic variance explained (PVE ? 0.05), but also demonstrated that more phenotypic variance was collectively explained by loci other than PRNP Genomic best linear unbiased prediction (GBLUP; n = 123,987 SNPs) with k-fold cross validation (k = 3; k = 5) and random sampling (n = 50 iterations) for the same cohort of 807 farmed U.S. white-tailed deer produced mean genomic prediction accuracies ? 0.81; thereby providing the necessary foundation for exploring a genomically-estimated CWD eradication program.

SUBMITTER: Seabury CM

PROVIDER: S-EPMC7144088 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Seabury Christopher M CM Oldeschulte David L DL Bhattarai Eric K EK Legare Dhruti D Ferro Pamela J PJ Metz Richard P RP Johnson Charles D CD Lockwood Mitchell A MA Nichols Tracy A TA

G3 (Bethesda, Md.) 20200409 4

The geographic expansion of chronic wasting disease (CWD) in U.S. white-tailed deer (<i>Odocoileus virginianus</i>) has been largely unabated by best management practices, diagnostic surveillance, and depopulation of positive herds. Using a custom Affymetrix Axiom single nucleotide polymorphism (SNP) array, we demonstrate that both differential susceptibility to CWD, and natural variation in disease progression, are moderately to highly heritable ([Formula: see text] among farmed U.S. white-tail ...[more]

PMID: 32122960

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Project description:Despite implementation of enhanced management practices, chronic wasting disease in US white-tailed deer (Odocoileus virginianus) continues to expand geographically. Herein, we perform the largest genome-wide association analysis to date for chronic wasting disease (n = 412 chronic wasting disease-positive; n = 758 chronic wasting disease-nondetect) using a custom Affymetrix Axiom single-nucleotide polymorphism array (n = 121,010 single-nucleotide polymorphisms), and confirm that differential susceptibility to chronic wasting disease is a highly heritable (h2= 0.611 ± 0.056) polygenic trait in farmed US white-tailed deer, but with greater trait complexity than previously appreciated. We also confirm PRNP codon 96 (G96S) as having the largest-effects on risk (P ≤ 3.19E-08; phenotypic variance explained ≥ 0.025) across 3 US regions (Northeast, Midwest, South). However, 20 chronic wasting disease-positive white-tailed deer possessing codon 96SS genotypes were also observed, including one that was lymph node and obex positive. Beyond PRNP, we also detected 23 significant single-nucleotide polymorphisms (P-value ≤ 5E-05) implicating ≥24 positional candidate genes; many of which have been directly implicated in Parkinson's, Alzheimer's and prion diseases. Genotype-by-environment interaction genome-wide association analysis revealed a single-nucleotide polymorphism in the lysosomal enzyme gene ARSB as having the most significant regional heterogeneity of effects on chronic wasting disease (P ≤ 3.20E-06); with increasing copy number of the minor allele increasing susceptibility to chronic wasting disease in the Northeast and Midwest; but with opposite effects in the South. In addition to ARSB, 38 significant genotype-by-environment single-nucleotide polymorphisms (P-value ≤ 5E-05) were also detected, thereby implicating ≥ 36 positional candidate genes; the majority of which have also been associated with aspects of Parkinson's, Alzheimer's, and prion diseases.

Project description:White-tailed deer are a culturally and economically important game species in North America, especially in South Texas. The recent discovery of chronic wasting disease (CWD) in captive deer facilities in Texas has increased concern about the potential emergence of CWD in free-ranging deer. The concern is exacerbated because much of the South Texas region is a semi-arid environment with variable rainfall, where precipitation is strongly correlated with fawn recruitment. Further, the marginally productive rangelands, in combination with erratic fawn recruitment, results in populations that are frequently density-independent, and thus sensitive to additive mortality. It is unknown how a deer population in semi-arid regions would respond to the presence of CWD. We used long-term empirical datasets from a lightly harvested (2% annual harvest) population in conjunction with 3 prevalence growth rates from CWD afflicted areas (0.26%, 0.83%, and 2.3% increases per year) via a multi-stage partially deterministic model to simulate a deer population for 25 years under four scenarios: 1) without CWD and without harvest, 2) with CWD and without harvest, 3) with CWD and male harvest only, and 4) with CWD and harvest of both sexes. The modeled populations without CWD and without harvest averaged a 1.43% annual increase over 25 years; incorporation of 2% annual harvest of both sexes resulted in a stable population. The model with slowest CWD prevalence rate growth (0.26% annually) without harvest resulted in stable populations but the addition of 1% harvest resulted in population declines. Further, the male age structure in CWD models became skewed to younger age classes. We incorporated fawn:doe ratios from three CWD afflicted areas in Wisconsin and Wyoming into the model with 0.26% annual increase in prevalence and populations did not begin to decline until ~10%, ~16%, and ~26% of deer were harvested annually. Deer populations in variable environments rely on high adult survivorship to buffer the low and erratic fawn recruitment rates. The increase in additive mortality rates for adults via CWD negatively impacted simulated population trends to the extent that hunter opportunity would be greatly reduced. Our results improve understanding of the potential influences of CWD on deer populations in semi-arid environments with implications for deer managers, disease ecologists, and policy makers.

Dataset Information

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

Publications

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

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