Natural scrapie and PrP genotype: case-control studies in British sheep.

Natural scrapie in sheep is associated with polymorphisms of the PrP gene, particularly at amino acid codons 136, 154 and 171. This paper reports the results of nine scrapie case-control studies in Bleu du Maine, Herdwick, Merino x Shetland, Poll Dorset, Scottish Halfbred, Shetland, Soay, Suffolk and Swaledale sheep from British flocks affected by scrapie. In some outbreaks, scrapie was found to occur only in animals with at least one PrP allele encoding valine at codon 136 (V136), usually a relatively rare allele in healthy controls. In other outbreaks, the V136, PrP allele was either not found or was not an absolute prerequisite for scrapie to develop. Although scrapie had a strong tendency to affect sheep with PrP genotypes homozygous for glutamine at codon 171 (QQ171), these genotypes (QQ171 but varying at other codon positions) were relatively common in healthy controls. The reliable prediction of scrapie susceptibility in previously uninvestigated sheep flocks will therefore require information at least about PrP genotypes at codons 136 and 171.