Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes

Abstract

Natural scrapie in a closed flock of South Country Cheviot sheep has resulted in 45 deaths between 1986 and 1995. Of these cases, 35 sheep have been analysed for disease-linked PrP gene polymorphisms and all encode valine at codon 136 on at least one allele with 77% homozygous (VV136) and 23% valine/alanine heterozygotes (VA136). Mean survival time was 907 and 1482 days for VV136 and VA136 scrapie affected animals respectively. VV136 animals were all at great risk of disease if allowed to live long enough. However scrapie occurred only in a specific subgroup of VA136 sheep, survival advantage depending on VA136 animals being heterozygous for other polymorphisms at codons 154 or 171. The flock history has been recorded in great detail since its foundation in 1960 however there was no strong evidence for simple maternal or paternal transmission of disease other than inheritance of PrP genotype.

A prion disease of cervids: Chronic wasting disease

“…The Prnp genotype seemed to impact the infection kinetics in that mule deer that were SF heterozygous at codon 225 showed a delay in PrP Sc spread; PrP Sc was not detectable in the brain until 16 months postinoculation which was 13 months later than the 225SS deer. Perhaps the 225F allele confers a dominant negative effect on the kinetics of this CWD strain, as has been described in sheep, where the 171R allele has been shown to have a dominant negative effect on prion susceptibility [20,33].…”

The evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep

“…The rearing rate in Shropshire ewes without an ARR allele was also significantly higher than for ARR heterozygotes (96.7% versus 86.5%; P < 0.05). The number of genotyped animals was small (44) and thus these findings should be treated with some caution.…”

“…The AHQ, ARH, ARQ, and VRQ alleles are generally associated with susceptibility. The degree of, and the ranking for, susceptibility appears to be breed dependent, with the VRQ allele (when present within a breed) generally considered the most susceptible [7,8,31,44,61,64,77,79]. There is also evidence to suggest that polymorphisms at other codons within the PrP gene may modify the degree of resistance associated with the ARQ allele [82].…”

Epidemiology and control of scrapie within a sheep flock

“…There is good evidence for genetic variation in susceptibility to scrapie determined largely by alleles at the PrP locus (Hunter et al 1996) (Hunter et al 1996). It is not known whether`resistant' sheep cannot become infected or, by analogy with experimental infections of mice (Bruce et al 1991), whether the incubation period in these sheep is so long in relation to sheep life expectancy that clinical signs are never seen.…”