Abstract
BackgroundChronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including white-tailed (Odocoileus virginianus) and mule deer (Odocoileus hemionus), Rocky Mountain elk (Cervus elaphus nelsoni), and moose (Alces alces). A leucine variant at position 132 (132L) in prion protein of Rocky Mountain elk confers a long incubation time with CWD, but not complete resistance. However, variants in regulatory regions outside the open reading frame of PRNP have been associated with varying degrees of susceptibility to prion disease in other species, and some variants have been observed in similar regions of Rocky Mountain elk PRNP. Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L.FindingsThis study provided genomic sequence of all exons for PRNP of Rocky Mountain elk. Many functional sites in and around the PRNP gene region were sequenced, and this report approximately doubled (to 75) the number of known variants in this region. A haplotype-tagging approach was used to reduce the number of genetic variants required to survey this variation in the PRNP gene region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited genetic diversity in the PRNP gene region.ConclusionsThe presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar to a previous report. However after accounting for 132L, no association with CWD was found for any additional variants in the PRNP region (P > 0.05).
Highlights
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including white-tailed (Odocoileus virginianus) and mule deer (Odocoileus hemionus), Rocky Mountain elk (Cervus elaphus nelsoni), and moose (Alces alces)
The presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar to a previous report
After accounting for 132L, no association with CWD was found for any additional variants in the PRNP region (P > 0.05)
Summary
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including whitetailed and mule deer (Odocoileus virginianus and O. hemionus, respectively), Rocky Mountain elk (Cervus elaphus nelsoni), and moose (Alces alces) [1]. This invariably fatal disease can be associated with progressive physical wasting, often accompanied by behavioral changes including listlessness, decreased interaction with other animals, decreased responsiveness to environmental stimuli, and repetitive behaviors [1]. Genetic solutions may be possible for Rocky Mountain elk, and a leucine variant at position 132 (132L) in prion protein confers a long incubation time with CWD, but not complete resistance [9,10,11]. This study used a two-stage haplotype-tagging strategy to search for any variants in the PRNP gene region - whether previously known, discovered in this study, or as yet undiscovered - that may provide increased protection from CWD in Rocky Mountain elk
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