Location: Animal Disease ResearchTitle: Prion genotypes of scrapie-infected Canadian sheep 1998-2008) Author
Submitted to: Canadian Journal of Veterinary Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/24/2009
Publication Date: 7/12/2010
Publication URL: http://handle.nal.usda.gov/10113/56640
Citation: Harrington, N., Orourke, K.I., Feng, Y., Rendulich, J., Difruscio, C., Balachandran, A. 2010. Prion genotypes of scrapie-infected Canadian sheep 1998-2008. Canadian Journal of Veterinary Research. 74(3):228-232. Interpretive Summary: Scrapie is a fatal brain disease of sheep and goats. The disease is associated with a misfolded form of the prion protein, a protein found normally in tissues of sheep and goats. The first report of scrapie in Canada dates to 1938 and subsequent control programs have been hampered by the long incubation period and the often subtle clinical signs of disease. Susceptibility of individual sheep to the disease varies with the sheep's genetic background: although the normal form of the prion protein is found in all sheep, studies from the United Kingdom and Europe have demonstrated that small differences in its genetic composition determine whether a sheep is susceptible to scrapie following exposure in the flock. In this study, we analyzed the prion gene of 284 sheep diagnosed with scrapie through the Canadian scrapie control program. In addition, we compared the prion gene of infected sheep to that of uninfected flockmates in three large flocks recently identified as scrapie infected. The study demonstrated that a particular form of the gene identified as ARQ was the most common form found in infected sheep. This finding contrasts to observations in Europe and the United Kingdom, in which a form identified as VRQ was more common. Overall, however, all sheep with scrapie had genotypes considered to be susceptible to classical scrapie. This finding supports the current control program, in which all sheep with susceptible genotypes are removed from infected flocks and sheep with resistant genotypes are allowed to remain. This plan allows for more economical culling of the highest risk sheep while sparing sheep that are not at significant risk of scrapie. Future studies will examine the role of additional genetic markers for scrapie susceptibility.
Technical Abstract: Susceptibility to classical scrapie, the transmissible spongiform encephalopathy of sheep, is associated with polymorphisms in the PRNP gene encoding the prion protein precursor, particularly those resulting in amino acid substitutions at residues 136, 154, and 171. This finding offers the prospect of selective breeding for scrapie resistance. This report describes the PRNP genotypes of a large sample of Canadian sheep (n=284) with naturally occurring classical scrapie, sampled through the regulatory program from 1998 through 2009 and a case-control analysis of scrapie affected sheep (n=72) and their healthy flockmates (n=1990) from three recently identified flocks. Five major PRNP alleles, identified by the amino acid encoded at codons 136, 154 and 171 respectively, were found: ARQ, VRQ, ARR, ARH, and AHQ. Six of fifteen diploid genotypes were represented in the study. The most frequent haplotype and genotype were ARQ and ARQ/ARQ. The highly susceptible allele VRQ was found in only a small proportion (4.7%) of the infected sheep. The resistance-associated ARR haplotype was found in only 3 scrapie infected sheep and all three were heterozygous for the VRQ allele. These results show that the incidence of classical scrapie in the Canadian sheep population is associated with the ARQ/ARQ genotype, differing from findings in Europe and the United Kingdom in which the VRQ allele predominates in scrapie infected animals. The relative contributions of host genotype and scrapie strain remain to be resolved.