Prion protein allele A136 H154Q171 is associated with high susceptibility to scrapie in purebred and crossbred German Merinoland sheep.

Prion protein (PrP) genotypes were determined in eight sheep that have been tested positive for atypical scrapie from purebred or crossbred Merinoland sheep flocks in Germany and compared with the PrP genotypes of their flock mates. Two restriction fragment length polymorphism (RFLP) analyses were developed to determine all PRNP haplotypes occurring by variations at codons 136, 154 and 171. At least one copy of the A(136) H(154) Q(171) (AHQ) allele was found in all scrapie-positive sheep while the frequency of AHQ varied from over 23% to less than 3% in the whole flocks. There was a significant association between PrP genotype and a positive scrapie diagnosis over all flocks, suggesting a high scrapie susceptibility of PrP genotypes including the AHQ allele, at least in sheep of Merinoland type. These results argue that sheep with the AHQ allele are not generally less susceptible to scrapie and support the hypothesis that the influence of this allele on scrapie susceptibility may vary from flock to flock depending on genetic and/or epidemiological factors. This has to be considered when strategies for the eradication of scrapie in sheep are based on PrP genotypes.