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Title: Scrapie resistance in ARQ sheep

item Clawson, Michael - Mike
item Heaton, Michael - Mike
item Green, Benedict - Ben
item O'Rourke, Katherine
item Knowles Jr, Donald

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/5/2007
Publication Date: 1/2/2008
Citation: Laegreid, W.W., Clawson, M.L., Heaton, M.P., Green, B.T., Orourke, K.I., Knowles Jr, D.P. 2008. Scrapie resistance in ARQ sheep (abstract). Plant and Animal Genome XVI Conference. Poster No. P550.

Interpretive Summary:

Technical Abstract: Susceptibility of sheep to classical scrapie is strongly influenced by genetic variation in the ovine prion gene (PRNP), especially at amino acid residues 136, 154 and 171. Sheep with the A136R154R171 haplotype are considered resistant, while those homozygous for A136R154Q171 are susceptible. However, there is considerable variation in survival time in ARQ sheep exposed to scrapie, and in natural infections not all exposed ARQ sheep develop scrapie within their typical lifespan. The purpose of this study was to determine whether survival time of scrapie-exposed ARQ sheep is associated with nucleotide sequence variation elsewhere in ovine PRNP. Samples of DNA were obtained from a cohort of sheep that were orally exposed to scrapie and monitored for over 3,000 days. The diagnosis of scrapie was confirmed histologically and immunohistochemically. A set of six PCR amplicons spanning PRNP and containing 18 haplotype tagging SNPs (htSNP) were sequenced and htSNP haplotypes determined. On the background of one htSNP haplotype were minor alleles of four low frequency SNPs that were in strong linkage disequilibrium with each other and were associated with prolonged survival (p<0.001). Mean survival time of ARQ sheep heterozygous for these alleles was 1,458 days, versus 771 days for all other ARQ sheep (p<0.002). Two sheep in this study were homozygous for the alleles and did not develop scrapie during the observation period, suggesting that the effect of these alleles may be additive. These results indicate that survival of scrapie-exposed ARQ sheep is not homogenous and is associated with a set of four PRNP alleles among ARQ sheep, providing evidence that some ARQ sheep are genetically resistant to scrapie.