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Map of Illinois (orange) and Wisconsin (pink), showing the study area for samples collected between 2002 and 2010. Samples were collected from all counties in gray by hunter harvest or government culling. Counties within the CWD infection area (at least 5 confirmed cases of CWD during the sample period) are darkly shaded; statistical analyses of CWD susceptibility were restricted to individuals originating from these locations thus increasing the probability of disease exposure. Number of samples from each county is indicated below the county name.
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The sequence of the prion protein gene (PRNP) affects susceptibility to spongiform encephalopathies, or prion diseases in many species. In white-tailed deer, both coding and non-coding single nucleotide polymorphisms have been identified in this gene that correlate to chronic wasting disease (CWD) susceptibility. Previous studies examined individua...
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... sequences were determined for 703 deer by PCR and Sanger sequencing: 579 tested for CWD (105 testing positive, 474 for which CWD was not detected) and 124 that were not tested. Analyses of disease risk were performed using a reduced dataset (N D 240) consisting of deer originating in counties with more than 5 cases of CWD confirmed by government moni- toring between 2002-2010 (henceforth referred to as the "CWD infection area;" Fig. 1). Addi- tional tested and untested samples were obtained from areas with low risk of CWD (counties with fewer than 5 or no confirmed cases at the time of sampling) to better detect sequence variations, haplotypes, and diplo- types. Statistical significance was determined by logistic regression using the most frequent haplotype, diplotype, genotype, or nucleotide as the reference level. Within the analyzed 626 bp region of the PRNP gene 14 variable positions were identified, 10 previously reported 10,28 and 4 novel sites (299G/A, 308A/ T, 367G/A, and 372G/A). Of the 14 variable sites 6 are non-synonymous (3 novel and 3 pre- viously reported) and result in a change to the amino acid sequence ( Table 1). It is important to note that mutations at nt299, nt308, and nt367 (aa100S/N, aa103N/I and aa123A/T respectively) are of interest as the human equivalents (aa97, aa100, and aa120 respec- tively) are in close proximity to polymorphisms associated with prion disease susceptibility in humans. [31][32][33] Haplotypes were generated from unphased sequences using PHASE v2.1. 34,35 Twenty-four haplotypes were predicted from 703 deer (N=1406 possible haplotype copies), with hap- lotype A occurring most frequently ( Table 1). Nine haplotypes are found exclusively among negative (haplotypes L, Q, S, T, and W), posi- tive (haplotype R) or untested deer (haplotypes U, V, and X); however, each of these haplo- types is rare with a frequency of occurrence less than 1% ( Table 1). Seventeen haplotypes occurred within the CWD infection area and only haplotype C is significantly less likely to be found among deer infected with CWD (P < 0.001, OR D 0.240 and 95% CI D 0.104- 0.503) ( Table ...
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Since chronic wasting disease (CWD) was first identified nearly 50 years ago in a captive mule deer herd in the Rocky Mountains of the United States, it has slowly spread across North America through the natural and anthropogenic movement of cervids and their carcasses. As the endemic areas have expanded, so has the need for rapid, sensitive, and c...
Chronic wasting disease (CWD) continues to spread or be recognized in the United States, Canada, and Europe. CWD is diagnosed by demonstration of the causative misfolded prion protein (PrPCWD) in either brain or lymphoid tissue using immunodetection methods, with immunohistochemistry (IHC) recognized as the gold standard. In recent years, in vitro...
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy caused by prions that has spread across cervid species in North America since the 1960s and has recently been detected in Eurasian cervids. The Association of Zoos and Aquariums (AZA) considers CWD to be of major concern for cervids in AZA-accredited facilities because of th...
In sheep, scrapie is a fatal neurologic disease that is caused by a misfolded protein called a prion (designated PrPSc). The normal cellular prion protein (PrPC) is encoded by an endogenous gene, PRNP, that is present in high concentrations within the CNS. Although a broad range of functions has been described for PrPC, its entire range of function...
Assessments of the adaptive potential in natural populations are essential for understanding and predicting responses to environmental stressors like climate change and infectious disease. Species face a range of stressors in human‐dominated landscapes, often with contrasting effects. White‐tailed deer (Odocoileus virginianus; deer) are expanding i...
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... Even a single amino acid difference can impose a significant energy barrier on the misfolding process, thus slowing or even blocking the molecular event that drives prion disease pathogenesis and transmission dynamics [44]. This explains, for a large part, the sometimes-potent genetic modulation of prion disease susceptibility observed in scrapie [45][46][47][48] and CWD [49][50][51][52], which is governed by alteration of the PRNP gene causing amino acid substitutions in the PrP C structure. ...
Prion diseases are transmissible neurodegenerative disorders that affect humans and ruminant species consumed by humans. Ruminant prion diseases include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats and chronic wasting disease (CWD) in cervids. In 1996, prions causing BSE were identified as the cause of a new prion disease in humans; variant Creutzfeldt-Jakob disease (vCJD). This sparked a food safety crisis and unprecedented protective measures to reduce human exposure to livestock prions. CWD continues to spread in North America, and now affects free-ranging and/or farmed cervids in 30 US states and four Canadian provinces. The recent discovery in Europe of previously unrecognized CWD strains has further heightened concerns about CWD as a food pathogen. The escalating CWD prevalence in enzootic areas and its appearance in a new species (reindeer) and new geographical locations, increase human exposure and the risk of CWD strain adaptation to humans. No cases of human prion disease caused by CWD have been recorded, and most experimental data suggest that the zoonotic risk of CWD is very low. However, the understanding of these diseases is still incomplete (e.g., origin, transmission properties and ecology), suggesting that precautionary measures should be implemented to minimize human exposure.
... Nonsynonymous polymorphisms in PRNP gene sequences have different frequencies between CWD positive and CWD negative white-tailed deer, suggesting a protective effect for some protein-altering mutations [14,15]. A general overview of these variants across the family Cervidae is discussed by [16][17][18], [17] identified PRNP haplotype variants, and [18] inferred PrP proteoforms (protein variations encoded by a specific gene [19]) in white-tailed deer. Proteoform (PrP variant) A is overrepresented in CWD-positive individuals, while proteoforms C and F are underrepresented in CWD-positive individuals. ...
... Nonsynonymous polymorphisms in PRNP gene sequences have different frequencies between CWD positive and CWD negative white-tailed deer, suggesting a protective effect for some protein-altering mutations [14,15]. A general overview of these variants across the family Cervidae is discussed by [16][17][18], [17] identified PRNP haplotype variants, and [18] inferred PrP proteoforms (protein variations encoded by a specific gene [19]) in white-tailed deer. Proteoform (PrP variant) A is overrepresented in CWD-positive individuals, while proteoforms C and F are underrepresented in CWD-positive individuals. ...
... Both inferred haplotypes and protein translation was completed using DNA Sequence Polymorphism v6.12.03 (DnaSP6, [36]). Prion protein haplotype and PrP proteoform designations followed those of [17] and [18] respectively. Haplotype and PrP proteoform frequencies were calculated by taking the total number of haplotype or proteoform in each location/time and dividing it by the total number in the sample. ...
Chronic wasting disease (CWD) is a fatal, highly infectious prion disease that affects captive and wild cervids. Chronic wasting disease is the only known transmissible spongiform encephalopathy affecting free-ranging wildlife. In CWD-positive deer, some haplotypes of the prion protein gene PRNP are detected at lower frequencies as compared to CWD-negative deer, as are some variants of the prion protein PrP. Here, we examined wild, hunter-harvested CWD-negative white-tailed deer (Odocoileus virginianus) to determine whether there were geographical or temporal differences in the PRNP haplotypes, PRNP diplotypes, PrP proteoforms, and in the proportion of deer with at least one protective haplotype. We sampled 96-100 hunter-harvested deer per county at two time points in the Illinois counties of Jo Daviess, LaSalle, and Winnebago, chosen based on their geographic locations and known occurrence of CWD. The entire coding region of PRNP was sequenced, with haplotypes, diplotypes, and PrP proteoforms inferred. Across time, in Winnebago there was a significant increase in PrP proteoform F (p = 0.034), which is associated with a lower vulnerability to CWD. In every county, there was an increase over time in the frequency of deer carrying at least one protective haplotype to CWD, with a significant increase (p = 0.02) in the Jo Daviess County CWD infected region. We also found that primer combination was important as there was an 18.7% difference in the number of the deer identified as homozygous depending on primer usage. Current Illinois state management practices continue to remove CWD infected deer from locally infected areas helping to keep CWD prevalence low. Nonetheless, continued research on spatial and temporal changes in PRNP haplotypes, PrP proteoforms, and levels of deer vulnerability among Illinois deer will be important for the management of CWD within the state of Illinois and beyond.
... Variation in PRNP has been associated with differences in susceptibility to CWD in cervids. For example, in white-tailed deer (Odocoileus virginianus), two non-synonymous single nucleotide polymorphisms (SNPs) have been associated with reduced susceptibility to CWD: c.285A>C that encodes a histidine (H) instead of the more common glutamine (Q) at codon 95 and c.286G>A that encodes a serine (S) instead of the more common glycine (G) at codon 96 (Johnson et al., 2003;O'Rourke et al., 2004;Kelly et al., 2008;Brandt et al., 2015;Brandt et al., 2018). In mule deer (O. ...
Chronic wasting disease (CWD) is a prion disease of North American cervids. The transmission of CWD to endangered cervid species is of concern for captive breeding programs. Trans-species transmission could occur via direct contact with infected wild deer, or via prion contaminated fomites. Variation in the prion protein gene, PRNP , is associated with differences in CWD susceptibility among cervids. We therefore sequenced PRNP in 36 endangered Eld’s deer ( Rucervus eldii thamin ), detecting five synonymous and two non-synonymous SNPs. Three haplotypes were inferred, suggesting that genetic management in captive breeding programs has been effective at maintaining PRNP diversity. The haplotypes encoded two PrP protein variants. The more common Eld’s deer PrP variant encodes methionine at codon 208 and glutamine at codon 226. Because this protein variant is identical to a common PrP variant in white-tailed deer and mule deer and is especially common in white-tailed deer positive for CWD, we recommend reducing the frequency of this variant in the breeding stock, while implementing strict management practices to avoid exposure to wild North American cervids. The frequency of the other PrP variant, which differs from variants present in these North American cervids, was low. It has the potential to reduce susceptibility to CWD and thus could be increased in frequency. While PRNP haplotype frequencies should be shifted, genetic diversity should be maintained. Ultimately protein diversity may be protective should CWD infect the species, and trans-species polymorphisms are suggestive of past balancing selection and a potential fitness advantage for PRNP diversity.
... We inferred haplotypes based on combinations of genotypes at different polymorphic sites using the program PHASE v. 2.1 [55,56]. We performed five independent runs to evaluate consistency in the results, setting the parameters as follows: 100,000 iterations, burn-in of 10,000 and drawing samples every 100 iterations [27,57] and default phase thresholds (90%). In a previous study of a white-tailed deer population in Arkansas, Chafin et al. [47] found 19 PRNP haplotypes based on 14 polymorphic sites. ...
Chronic wasting disease (CWD) is a fatal encephalopathy affecting North American cervids. Certain alleles in a host’s prion protein gene are responsible for reduced susceptibility to CWD. We assessed for the first time variability in the prion protein gene of elk (Cervus canadensis) present in Pennsylvania, United States of America, a reintroduced population for which CWD cases have never been reported. We sequenced the prion protein gene (PRNP) of 565 elk samples collected over 7 years (2014–2020) and found two polymorphic sites (codon 21 and codon 132). The allele associated with reduced susceptibility to CWD is present in the population, and there was no evidence of deviations from Hardy-Weinberg equilibrium in any of our sampling years (p-values between 0.14 and 1), consistent with the lack of selective pressure on the PRNP. The less susceptible genotypes were found in a frequency similar to the ones reported for elk populations in the states of Wyoming and South Dakota before CWD was detected. We calculated the proportion of less susceptible genotypes in each hunt zone in Pennsylvania as a proxy for their vulnerability to the establishment of CWD, and interpolated these results to obtain a surface representing expected proportion of the less susceptible genotypes across the area. Based on this analysis, hunt zones located in the southern part of our study area have a low proportion of less susceptible genotypes, which is discouraging for elk persistence in Pennsylvania given that these hunt zones are adjacent to the deer Disease Management Area 3, where CWD has been present since 2014.
... Environmental factors influencing local persistence and spread of CWD include the proportion of urban and agricultural lands (O'Hara , soil clay content and pH (Dorak et al., 2017), deer habitat abundance, and deer density (Joly et al., 2006), terrain ruggedness, the extent of agriculture lands, proximity to rivers and creeks (Rees et al., 2012), the use of mineral licks (Plummer et al., 2018), fragmented habitats and large forest areas (Kelly et al., 2014;. Demographic and genetic factors influencing host susceptibility of deer to CWD include sex (Jennelle et al., 2014), age of the deer , genetic variability in the prion protein gene (Brandt et al., 2015;Miller & Walter, 2019;Rivera et al., 2019) and haplotypes encoding protective prion protein variants (Brandt et al., 2018;Ishida et al., 2020). Furthermore, haplotype information in cervid populations without CWD has been used to infer the risk of CWD infection in populations that did not have CWD (Perrin-Stowe et al., 2020). ...
In northern Illinois, chronic wasting disease (CWD) was first identified in free-ranging white-tailed deer (Odocoileus virginianus; hereafter referred to as "deer") in 2002. To reduce CWD transmission rates in Illinois, wildlife biologists have conducted locally focussed culling of deer since 2003 in areas where CWD has been detected. We used retrospective spatial, temporal and space-time scan statistical models to identify areas and periods where culling removed higher than expected numbers of CWD-positive deer. We included 490 Public Land Survey "sections" (∼2.59 km2 ) from 15 northern Illinois counties in which at least one deer tested positive for CWD between 2003 and 2020. A negative binomial regression model compared the proportion of CWD positive cases removed from sections with at least one CWD case detected in the previous years, "local area 1 (L1)," to the proportion of CWD cases in adjacent sections-L2, L3, and L4-designated by their increasing distance from L1. Of the 14,661 deer removed and tested via culling, 325 (2.22 %) were CWD-positive. A single temporal CWD cluster occurred in 2020. Three spatial clusters were identified, with a primary cluster located at the border of Boone and Winnebago counties. Four space-time clusters were identified with a primary cluster in the northern portion of the study area from 2003 to 2005 that overlapped with the spatial cluster. The proportion of CWD cases removed from L1 (3.92, 95% CI, 2.56-6.01) and L2 (2.32, 95% CI, 1.50-3.59) were significantly higher compared to L3. Focussing culling efforts on accessible properties closest to L1 areas results in more CWD-infected deer being removed, which highlights the value of collaborations among landowners, hunters, and wildlife management agencies to control CWD. Continuous evaluation and updating of the culling and surveillance programs are essential to mitigate the health burden of CWD on deer populations in Illinois.
... Sequences were translated using MEGA X v. 10 (Table 2). In Elad2, SNP c.413A>G encodes serine (S) at codon 138, which is also present in many deer taxa (Table 2); whereas in Elad2, asparagine (N) is encoded at codon 138 (as reported in fallow deer and some caribou; Amino acid sequences of PrP were aligned for some cervid taxa with PRNP haplotype sequence available in GenBank, along with Elad1 and Elad2 (Table 2). ...
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy caused by prions that has spread across cervid species in North America since the 1960s and recently spread to cervids in Eurasia. The Association of Zoos and Aquariums (AZA) considers CWD to be of major concern for cervids in AZA-accredited facilities because of the indirect transmission risk of the disease and the impact of CWD regulatory protocols on captive breeding programs. Vulnerability to CWD is affected by variation in the PRNP gene that encodes the prion protein. We therefore sequenced PRNP in Pere David’s deer ( Elaphurus davidianus ), a species that was extinct in the wild for more than a century, and descends from ca. 11 founders. In 27 individuals, we detected two PRNP haplotypes, designated Elad1 (51 of 54 chromosomes) and Elad2 (3 of 54 chromosomes). The two haplotypes are separated by four single nucleotide polymorphisms (SNPs), three of which are non-synonymous. Both Elad1 and Elad2 have polymorphisms that in other cervid taxa are associated with reduced vulnerability to CWD. The two haplotypes are more similar in sequence to PRNP in other cervids than to each other. This suggests that PRNP in cervids may have been under long-term balancing selection, as has been shown for PRNP in non-cervid taxa, and which could account for the presence of multiple haplotypes among founders. There may be a fitness benefit in maintaining both PRNP haplotypes in the species because variation in the prion amino acid sequence can limit transmission of CWD.
... Initially, it was thought that a virus caused TSEs such as CWD, whereas the prion model is now the accepted root cause (Prusiner, 1982;Diringer, 2000;Zabel and Reid, 2015;Brandt et al., 2015;Herbst et al., 2017;see Manuelidis, 2004). It is common today to read statements such as: "These unique infectious agents [prions] exist in a wide variety of "strains"" (Morales, 2017;Espinosa et al., 2020), which has a relatively long history (Dickinson et al., 1968;Caughey et al., 1998). ...
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.
... Susceptibility and clinical progression are associated with non-synonymous and synonymous genetic variation in the functional prion protein gene (PRNP; Chafin et al., 2020;Güere et al., 2020). Single-nucleotide polymorphisms (SNPs) at nucleotide (nt) 60, nt153, nt285, nt286, nt555, and nt676 in deer PRNP have been associated with altered CWD susceptibility or pathogenic processes (Brandt et al., 2015(Brandt et al., , 2018Johnson, Johnson et al., 2006;Wilson et al., 2009). The presence of CWD appears to affect population PRNP allele frequencies over space and time due to selection (Robinson et al., 2012); however, altered CWD susceptibility and pathogenic processes are clearly polygenic traits (Seabury et al., 2020) and disease spread is different in structured populations, which might require different wildlife management practices (Chafin et al., 2020). ...
... The presence of asparagine (N) at aa138 (nt413A) indicates amplification of the pseudogene (Brandt et al., 2015); we therefore filtered out all sequences with this site. SNPs with a total frequency of occurrence of 1% or less were excluded from the analysis. ...
... Haplotype 1 (f = 0.12) did not include any non-synonymous substitutions. Haplotype A (f = 0.30) and Haplotype B (f = 0.25) reported by Brandt et al. (2015Brandt et al. ( , 2018 from northern Illinois were also detected as Haplotype 16 (f = 0.09) and Haplotype 7 (f = 0.05), respectively. ...
Assessments of the adaptive potential in natural populations are essential for understanding and predicting responses to environmental stressors like climate change and infectious disease. Species face a range of stressors in human‐dominated landscapes, often with contrasting effects. White‐tailed deer (Odocoileus virginianus; deer) are expanding in the northern part of their range following decreasing winter severity and increasing forage availability. Chronic wasting disease (CWD), a prion disease affecting deer, is likewise expanding and represents a major threat to deer and other cervids. We obtained tissue samples from free‐ranging deer across their native range in Ontario, Canada which has yet to detect CWD in wild populations. We used high‐throughput sequencing to assess neutral genomic variation, and variation in the prion protein gene (PRNP) that is partly responsible for the protein misfolding when deer contract CWD. Neutral variation revealed a high number of rare alleles and no population structure, and demographic models suggested a rapid historical population expansion. Allele frequencies of PRNP variants associated with CWD susceptibility and disease progression were evenly distributed across the landscape and consistent with deer populations not infected with CWD. We estimated the selection coefficient of CWD, with simulations showing an observable and rapid shift in PRNP allele frequencies that coincides with the start of a novel CWD outbreak. Sustained surveillance of genomic and PRNP variation can be a useful tool for guiding management practices, which is especially important for CWD‐free regions where deer are managed for ecological and economic benefits.
... Native Pet 1 4. Proximity to a known positive ( Figure 7D) -This risk modifier accounts for increased risk associated with proximity to the nearest known positive CWD sample, either within or outside of the state. 5. Genetic risk ( Figure 7E) -This risk modifier accounts for increased risk associated with lower frequencies of PRNP haplotype C in the white-tailed deer population within a county; haplotype C has been associated with somewhat reduced susceptibility to CWD (Brandt et al. 2015). The county frequencies of haplotype C were determined in a statewide white-tailed deer genetics study (Douglas et al. 2019). ...
The Arkansas Game and Fish Commission's Chronic Wasting Disease Management and Response Plan for implementation from 2021 to 2025.
... Two non-synonymous polymorphisms within the prion gene (PRNP) resulting in changes to amino acids 95 (Q95H) and 96 (G96S), have been most commonly found to be associated with reduced disease susceptibility in white-tailed deer [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. While neither have been shown to provide complete protection from CWD infection, they have been linked to reductions in genotype-specific prevalence rates [26,[29][30][31]36] or increased duration of incubation [37]. ...
... Of these samples, 185 were CWD-positive, 332 were CWD non-detected, and an additional 51 CWD non-detected were paired to CWD-positives to control for sex, age, and harvest location ( Figure 1). Within the analysed 625bp region of the PRNP gene, we detected 12 single nucleotide polymorphisms (SNPs), 9 of which had been previously reported [22,29,33,36,[38][39][40][41]. Of the 12 SNPs, 5 were non-synonymous, resulting in a change ...
... Full associated sequences have been deposited in GenBank under accession numbers MZ913400 -MZ913401. Thirteen haplotypes were predicted from the 12 SNPs, 11 of which have previously been described [22,40,41]. Of the 13 haplotypes, B was most common (n = 368) and was used as the reference in logistic regression. ...
Chronic Wasting Disease (CWD), a well-described transmissible spongiform encephalopathy of the Cervidae family, is associated with the aggregation of an abnormal isoform (PrPCWD) of the naturally occurring host prion protein (PrPC). Variations in the PrP gene (PRNP) have been associated with CWD rate of infection and disease progression. We analysed 568 free-ranging white-tailed deer (Odocoileus virginianus) from 9 CWD-positive Michigan counties for PRNP polymorphisms. Sampling included 185 CWD-positive, 332 CWD non-detected, and an additional 51 CWD non-detected paired to CWD-positives by sex, age, and harvest location. We found 12 polymorphic sites of which 5 were non-synonymous and resulted in a change in amino acid composition. Thirteen haplotypes were predicted, of which 11 have previously been described. Using logistic regression, consistent with other studies, we found haplotypes C (OR = 0.488, 95% CI = 0.321–0.730, P < 0.001) and F (OR = 0.122, 95% CI = 0.007–0.612, P < 0.05) and diplotype BC (OR = 0.340, 95% CI = 0.154–0.709, P < 0.01) were less likely to be found in deer infected with CWD. As has also been documented in other studies, the presence of a serine at amino acid 96 was less likely to be found in deer infected with CWD (P < 0.001, OR = 0.360 and 95% CI = 0.227–0.556). Identification of PRNP polymorphisms associated with reduced vulnerability to CWD in Michigan deer and their spatial distribution can help managers design surveillance programmesand identify and prioritize areas for CWD management.
