PrP gene polymorphism and natural scrapie in Icelandic sheep

Abstract

The association between scrapie and polymorphism of the prion protein (PrP) gene was studied in the Icelandic sheep breed. Polymorphism of the three codons, 136, 154 and 171, that are important for scrapie susceptibility was determined. A BspHI restriction analysis was used to study the alleles of codons 136 and 154, while density gradient gel electrophoresis (DGGE) was used to analyse codon 171 and detect new polymorphisms. The PrP allelic variant, VRQ (amino acids at codons 136, 154 and 171), was found to be highly statistically associated with scrapie, whereas the allelic variant, AHQ, was never found in scrapie-affected animals, a finding that is statistically significant. Iceland has a few scrapie-free regions, which are a part of a quarantine network. Homozygotes for the VRQ variant were found there at a low frequency, indicating that genetic susceptibility is not enough for scrapie to develop and further evidence for the infectious nature of the disease. A comparison of PrP genotypes between sheep outside and within the scrapie-free zones revealed an increase in the AHQ allelic variant in the latter. No polymorphism was found at codon 171 in a total of 932 sheep studied, all individuals having the glutamine allele. Two novel, rare PrP alleles were found using DGGE at codons 138 and 151, i.e. S138N and R151C. Their relevance to scrapie is still unclear, but the former was found in scrapie-affected sheep as well as healthy sheep, whereas the latter was only found in healthy sheep.

PrPgenetics in ruminant transmissible spongiform encephalopathies

“…When comparing averages from different breeds in different countries the AHQ allele frequency range appears to be 0.2% (USA) [21] to 12.5% (Norway) [68,88]. The mean of the AHQ frequency for the 20 studies (see above) is 6.3% and regional frequencies are 2.5% for Italy and Spain [1,2,4,27], 3.8% for Iceland [86], 9.6% for Greece [12,24] and 7.1% for New Zealand [14]. These data suggest that susceptible genotypes are available in most populations and also that genetic screening could be used for susceptibility control.…”

“…A survey conducted for this review of more than 20 studies [1,2,4,14,20,21,23,24,27,38,54,64,68,69,82,83,[86][87][88]90] reporting on sheep populations from 15 different countries in Europe, America and Asia revealed that so far all but one (Iceland) presented significant frequencies of all five major alleles (ARQ; ARR; AHQ; VRQ; ARH) in their sheep. Iceland appears not to have any ARR animals [86]. The allele frequency averaged over all animals in these studies were 56% ARQ, 30% ARR, 6% AHQ, 5% VRQ and 3% ARH.…”

“…Indeed, the question whether there are alleles other than ARR and AHQ associated with resistance to classical scrapie have been addressed frequently. In Icelandic scrapie outbreaks carriers of the AC 151 RQ allele were absent from affected animals [86]. Experimental challenges with BSE of ARP 168 Q/ARL 168 Q sheep resulted in survivors [37].…”

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

“…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].…”

The Clinical Neurology of Scrapie in Irish Sheep

“…There is much evidence for the role of the PrP genotype in susceptibility to scrapie and in determination of the incubation period. 15,23,53,54 There is less direct evidence for the role of genotype in the type of clinical pattern shown, although the form of clinical expression may be determined by genotype and influenced by strain type. The effects of agent strain and host genotype on PrP Sc accumulation in the brain have been reported.…”