Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes

Summary Natural scrapie in a closed flock of South Country Cheviot sheep has resulted in 45 deaths between 1986 and 1995. Of these cases, 35 sheep have been analysed for disease-linked PrP gene polymorphisms and all encode valine at codon 136 on at least one allele with 77% homozygous (VV₁₃₆) and 23% valine/alanine heterozygotes (VA₁₃₆). Mean survival time was 907 and 1482 days for VV₁₃₆ and VA₁₃₆ scrapie affected animals respectively. VV₁₃₆ animals were all at great risk of disease if allowed to live long enough. However scrapie occurred only in a specific subgroup of VA₁₃₆ sheep, survival advantage depending on VA₁₃₆ animals being heterozygous for other polymorphisms at codons 154 or 171. The flock history has been recorded in great detail since its foundation in 1960 however there was no strong evidence for simple maternal or paternal transmission of disease other than inheritance of PrP genotype.