The primary sequence of the prion protein affects susceptibility to transmissible spongiform encephalopathies, or prion diseases, in mice, sheep and humans. The Prnp gene sequence of free-ranging, Wisconsin white-tailed deer was determined and the Prnp genotypes of chronic wasting disease (CWD)-positive and CWD-negative deer were compared. Six amino acid changes were identified, two of which were located in pseudogenes. Two alleles, a QRK polymorphism at codon 226 and a single octapeptide repeat insertion into the pseudogene, have not been reported previously. The predominant alleles -wild-type (Q95, G96 and Q226) and a G96S polymorphism -comprised almost 98 % of the Prnp alleles in the Wisconsin white-tailed deer population. Comparison of the allelic frequencies in the CWD-positive and CWD-negative deer suggested that G96S and a Q95H polymorphism were linked to a reduced susceptibility to CWD. The G96S allele did not, however, provide complete resistance, as a CWD-positive G96S/G96S deer was identified. The G96S allele was also linked to slower progression of the disease in CWD-positive deer based on the deposition of PrP CWD in the obex region of the medulla oblongata.Although the reduced susceptibility of deer with at least one copy of the Q95H or G96S allele is insufficient to serve as a genetic barrier, the presence of these alleles may modulate the impact of CWD on white-tailed deer populations.

Chronic wasting disease (CWD) is a fatal disease of white‐tailed deer (Odocoileus virginianus) caused by transmissible protease‐resistant prions. Since the discovery of CWD in southern Wisconsin in 2001, more than 20,000 deer have been removed from a >2,500‐km2 disease eradication zone surrounding the three initial cases. Nearly all deer removed were tested for CWD infection and sex, age, and harvest location were recorded. Our analysis used data from a 310‐km2 core study area where disease prevalence was higher than surrounding areas. We found no difference in harvest rates between CWD infected and noninfected deer. Our results show that the probability of infection increased with age and that adult males were more likely to be infected than adult females. Six fawns tested positive for CWD, five fawns from the core study area, including the youngest (5 months) free‐ranging cervid to test positive. The increase in male prevalence with age is nearly twice the increase found in females. We concluded that CWD is not randomly distributed among deer and that differential transmission among sex and age classes is likely driving the observed patterns in disease prevalence. We discuss alternative hypotheses for CWD transmission and spread and, in addition, discuss several possible nonlinear relationships between prevalence and age. Understanding CWD transmission in free‐ranging cervid populations will be essential to the development of strategies to manage this disease in areas where CWD is found, as well as for surveillance strategies in areas where CWD threatens to spread.

ABSTRACT:Chronic wasting disease (CWD) is a fatal, emerging disease of cervids associated with transmissible protease-resistant prion proteins. The potential for CWD to cause dramatic declines in deer and elk populations and perceived human health risks associated with consuming CWDcontaminated venison have led wildlife agencies to embark on extensive CWD control programs, typically involving culling to reduce deer populations. We characterized the spatial distribution of CWD in white-tailed deer (Odocoileus virginianus) in Wisconsin to facilitate CWD management. We found that CWD prevalence declined with distance from a central location, was locally correlated at a scale of 3.6 km, and was correlated with deer habitat abundance. The latter result is consistent with patterns expected for a positive relationship between density and prevalence of CWD. We recommend management activities focused on culling in geographic areas with high prevalence to have the greatest probability of removing infected individuals. Further research is needed to elucidate the factors involved in CWD spread and infection rates, especially the role of density-dependent transmission.

Abstract. In September 2002, chronic wasting disease (CWD), a prion disorder of captive and wild cervids, was diagnosed in a white-tailed deer (Odocoileus virginianus) from a captive farm in Wisconsin. The facility was subsequently quarantined, and in January 2006 the remaining 76 deer were depopulated. Sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (PrP CWD ) in at least one tissue; the prevalence of positive staining was high even in young deer. Although none of the deer displayed clinical signs suggestive of CWD at depopulation, 49 deer had considerable accumulation of the abnormal prion in the medulla at the level of the obex. Extraneural accumulation of the abnormal protein was observed in 59 deer, with accumulation in the retropharyngeal lymph node in 58 of 59 (98%), in the tonsil in 56 of 59 (95%), and in the rectal mucosal lymphoid tissue in 48 of 58 (83%). The retina was positive in 4 deer, all with marked accumulation of prion in the obex. One deer was considered positive for PrP CWD in the brain but not in the extraneural tissue, a novel observation in white-tailed deer. The infection rate in captive deer was 20-fold higher than in wild deer. Although weakly related to infection rates in extraneural tissues, prion genotype was strongly linked to progression of prion accumulation in the obex. Antemortem testing by biopsy of rectoanal mucosal-associated lymphoid tissue (or other peripheral lymphoid tissue) may be a useful adjunct to tonsil biopsy for surveillance in captive herds at risk for CWD infection.

Abstract. An effective live animal diagnostic test is needed to assist in the control of chronic wasting disease (CWD), which has spread through captive and wild herds of white-tailed deer (Odocoileus virginianus) in Canada and the United States. In the present study, the diagnostic accuracy of rectal mucosa biopsy sample testing was determined in white-tailed deer from 4 CWD-infected captive herds. Specifically, the current study compared the immunohistochemical detection of disease-associated prion protein in postmortem rectal mucosa biopsy samples to the CWD status of each deer as determined by immunodiagnostic evaluations of the brainstem at the obex, the medial retropharyngeal lymph node, and the palatine tonsil. The effects of age, sex, genotype, and disease progression were also evaluated. Diagnostic sensitivity on rectal biopsy samples for CWD in white-tailed deer ranged from 63% to 100%; the pooled estimate of sensitivity was 68% with 95% confidence limits (95% CLs) of 49% and 82%. However, diagnostic sensitivity was dependent on genotype at prion protein gene (PRNP) codon 96 and on disease progression as assessed by obex grade. Diagnostic sensitivity was 76% (95% CLs: 49%, 91%) for 96GG deer but only 42% (95% CLs: 13%, 79%) for 96GS deer. Furthermore, diagnostic sensitivity was only 36% for deer in the earliest stage of disease (obex grade 0) but was 100% for deer in the last 2 stages of preclinical disease (obex grades 3 and 4). The overall diagnostic specificity was 99.8%. Selective use of antemortem rectal biopsy sample testing would provide valuable information during disease investigations of CWD-suspect deer herds.