We have investigated the correlation between restriction fragment length polymorphisms of the scrapie-associated fibril protein (PrP) gene and the incidence of natural scrapie in British sheep during the period from July 1988 to November 1990. Sixty percent of the scrapie-positive animals studied were homozygous for a 6·8 kb RI fragment (e1) and a further 26% carried e1 as heterozygotes. This fragment is linked to susceptibility to experimental scrapie in a closed flock of Cheviot sheep. Twelve percent of cases were found to be homozygous for a 4·4 kb RI fragment (e3) which in the Cheviot flock has been linked to relative resistance to scrapie. A third RI fragment of 5·2 kb (e2) has also been found but is relatively rare and has not yet been associated with scrapie susceptibility. Four sets of flocks affected by natural outbreaks of scrapie divided into two groups. In three of these flocks, all scrapie cases carried e1 with high frequencies of e1e1 homozygotes. In the fourth, there were no e1e1 scrapie cases; all scrapie sheep carried e3 in approximately equal numbers of heterozygotes and homozygotes.


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