Lambs with Scrapie Susceptible Genotypes Have Higher Postnatal Survival

Rami M Sawalha,Beatriz Villanueva,Susan Brotherstone,Joanne Conington,Björn Brembs

doi:10.1371/journal.pone.0001236

Rami M Sawalha, Beatriz Villanueva + Show 3 more

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https://doi.org/10.1371/journal.pone.0001236

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Abstract

BackgroundPrion protein (PrP) alleles associated with scrapie susceptibility persist in many sheep populations even with high frequencies despite centuries of selection against them. This suggests that scrapie susceptibility alleles have a pleiotropic effect or are associated with fitness or other traits that have been subject to selection.Methodology/Principal FindingsWe genotyped all lambs in two scrapie-free Scottish Blackface sheep flocks for polymorphisms at codons 136, 154 and 171 of the PrP gene. We tested potential associations of the PrP genotype with lamb viability at birth and postnatal survival using a complementary log-log link function and a Weibull proportional hazard model, respectively. Here we show there is an association between PrP genotype, as defined by polymorphisms at codons 154 ad 171, and postnatal lamb survival in the absence of scrapie. Sheep carrying the wild-type ARQ allele have higher postnatal survival rates than sheep carrying the more scrapie-resistant alleles (ARR or AHQ).ConclusionThe PrP genotypes associated with higher susceptibility to scrapie are associated with improved postnatal survival in the absence of the disease. This association helps to explain the existence, and in many instances the high frequency, of the ARQ allele in sheep populations.

Highlights

The polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene have been shown to be associated with susceptibility to scrapie and to have a major effect on the survival of infected animals [1,2]
Examples of such genes include interleukin 2 receptor alpha, a gene involved in antibody production [5]; the gene coding for centromere protein B, an antibody binding protein [6,7]; and the matrix metalloproteinase 9 gene [8] which may have a role in tumor invasion and metastasis [9]
Genetic-based scrapie eradication programs ignore the possibility of association of Prion protein (PrP) gene with other traits and rely on polymorphisms at three codons of the PrP gene through selecting in favor of the alleles known to confer the highest resistance (e.g. ARR) and against those associated with the highest susceptibility (e.g. VRQ)

Summary

Introduction

The polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene have been shown to be associated with susceptibility to scrapie and to have a major effect on the survival of infected animals [1,2]. The persistence of PrP alleles associated with scrapie susceptibility suggests that the gene has a pleiotropic effect or is linked to other genes on ovine chromosome 13 that affect fitness, health or performance in the absence of scrapie. Prion protein (PrP) alleles associated with scrapie susceptibility persist in many sheep populations even with high frequencies despite centuries of selection against them This suggests that scrapie susceptibility alleles have a pleiotropic effect or are associated with fitness or other traits that have been subject to selection. The PrP genotypes associated with higher susceptibility to scrapie are associated with improved postnatal survival in the absence of the disease This association helps to explain the existence, and in many instances the high frequency, of the ARQ allele in sheep populations

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Conclusion