The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks

The amino-acid sequence of the PrP protein plays an important role in deter mining whether sheep are susceptible to scrapic. Although the genetics of s crapie susceptibility are now well understood, there have been few studies of the PrP gene at the population level, especially in commercially farmed sheep. Here we describe the PrP genetic profiles of the breeding stock of f our UK sheep flocks, comprising nearly 650 animals in total. Two flocks had been scrapie affected for about eight years and two were scrapie free. Scr apie-resistant PrP genotypes predominated in all flocks but highly suscepti ble genotypes were present in each case. The distribution of PrP genotypes was similar in the scrapie-affected and scrapie-free flocks. The former, ho wever, showed a slight but significant skew towards more susceptible genoty pes despite their previous losses of susceptible sheep. Surprisingly, this skew was apparent in younger, but not older, sheep. We suggest that these p atterns may occur if sheep Becks destined to become scrapie affected are pr edisposed by a genetic profile skewed towards susceptibility The age struct ure of the scrapie-affected flocks suggests that the number of losses attri butable directly or indirectly to scrapie considerably exceeds that recogni zed by the farmers, and also that significant losses may occur even in shee p of a moderately susceptible genotype. Similar patter ns were not detected in the scrapie-free flocks, indicating that these losses are associated wi th scrapie infection as well as genotype.