The incubation period of scrapie in sheep is controlled by the gene which has two alleles (sA and pA). Following experimental challenge with SSBP/1 scrapie, a short incubation period is conferred by the partially dominant sA allele. Restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene are associated with the alleles. By sequencing the protein coding region of the PrP gene in Cheviot sheep selected for differing genotypes, we have found four PrP protein variants which differ at three positions: amino acid 112 (Ala/Val), amino acid 130 (Arg/His) and amino acid 147 (Arg/Gln). The Val 112 variant can be distinguished at the DNA level by an XI restriction site which is not present in the Ala 112 form. Val 112 appears to be linked to a short incubation period of experimentally induced scrapie in the Cheviot sheep and therefore with the sA allele. These results provide new evidence that the PrP protein may be a product of the locus.


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