Submitted to: BMC Research Notes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 18, 2010
Publication Date: November 18, 2010
Citation: White, S.N., Spraker, T.R., Reynolds, J.O., Orourke, K.I. 2010. Association analysis of PRNP gene region with chronic wasting disease in Rocky Mountain elk. BMC Research Notes. 3:314. Interpretive Summary: Background: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of Rocky Mountain elk. One genetic variant in the PRNP gene (termed 132L) was previously reported to delay the onset of CWD but does not provide complete resistance. However, other variants in gene regulatory regions might provide increased protection against CWD, either alone or in combination with the 132L variant. Findings: This study extended the genomic sequence available, including all exons for PRNP, and approximately doubled (to 75) the number of known variants in this gene region. Since these genetic variants are arranged in linear combinations called haplotypes, it is possible to reduce the cost and time required to survey them using a technique called haplotype-tagging, which was used to survey the PRNP gene region of 559 elk. A relatively small number (8) of haplotypes were observed, reflecting limited genetic diversity. Conclusions: The presence of the 132L variant 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 additional association with CWD was found for any other variants in the PRNP region (P>0.05). This research suggests there are no common genetic variants in the PRNP gene region of elk that would give resistance to CWD and suggests that other approaches to CWD should be pursued, possibly including rare variants and/or other genes that might contribute to resistance.
Technical Abstract: Background: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including whitetail (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 the prion gene 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. Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L. Findings: This 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. Conclusions: 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. However after accounting for 132L, no association with CWD was found for any additional variants in the PRNP region (P>0.05).