Invasive Species Compendium

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Abstract

Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie.

Abstract

Denaturing gradient gel electrophoresis (DGGE) was used to detect polymorphisms in the sheep PrP gene. In addition to the previously described polymorphisms at codons 136, 154 and 171, a G→T transition was identified at codon 171. This transition is responsible for a glutamine to histidine substitution. An arginine to glutamine substitution at this position has been described previously. DGGE identified 5 different combinations of these polymorphisms within the PrP gene representing 5 allelic variants, which were cloned and sequenced. Based on the triplet sequences present at codons 136, 154 and 171 these allelic variants were designated PrPVRQ, PrPARR, PrPARQ, PrPARH and PrPAHQ. To determine the association of these allelic variants with natural scrapie, 34 scrapie affected and 91 healthy control Texel sheep were screened for the presence of these allelic variants. In these 2 groups, the 5 variants gave rise to 13 different genotypes. The distribution of the allelic variants among both groups showed marked differences. The PrPVRQ variant was present with high frequency in scrapie affected sheep, whereas the PrPARR variant was almost exclusively present in healthy sheep. The other variants, PrPARQ and PrPARH, were found in both groups with equal frequencies. These results suggest modulation of disease susceptibility in these Texel sheep by at least 5 different PrP allelic variants, with the PrPVRQ and PrPARR alleles acting in a dominant, but opposite fashion over the PrPARQ and PrPARH alleles. The frequency of the PrPAHQ variant was too low to draw any conclusions.