PrP gene polymorphism and natural scrapie in Icelandic sheep

The association between scrapie and polymorphism of the prion protein (PrP) gene was studied in the Icelandic sheep breed. Polymorphism of the three c odons, 136, 154 and 171, that are important for scrapie susceptibility was determined. A BspHI restriction analysis was used to study the alleles of c odons 136 and 154, while density gradient gel electrophoresis (DGGE) was us ed to analyse codon 171 and detect new polymorphisms. The PrP allelic varia nt, VRQ (amino acids at codons 136, 154 and 171), was found to be highly st atistically associated with scrapie, whereas the allelic variant, AHQ, was never found in scrapie-affected animals, a finding that is statistically si gnificant. Iceland has a few scrapie-free regions, which are a part of a qu arantine network. Homozygotes for the VRQ variant were found there at a low frequency, indicating that genetic susceptibility is not enough for scrapi e to develop and further evidence for the infectious nature of the disease. A comparison of PrP genotypes between sheep outside and within the scrapie -free zones revealed an increase in the AHQ allelic variant in the latter. No polymorphism was found at codon 171 in a total of 932 sheep studied, all individuals having the glutamine allele, Two novel, rare PrP alleles were found using DGGE at codons 138 and 151, i.e. S138N and R151C. Their relevan ce to scrapie is still unclear, but the former was found in scrapie-affecte d sheep as well as healthy sheep, whereas the latter was only found in heal thy sheep.