Identification of a new leucine haplotype (ALQ) at codon 154 in the ovine prion protein gene in Spanish sheep

Abstract

Genetic susceptibility to scrapie is closely linked to variations at codons 136, 154, and 171 of the prion protein (PRNP) gene. This association between the PRNP genotype and susceptibility to scrapie is the basis of breeding programs for scrapie resistance in different countries. In this paper, we describe the method used with 2 Spanish dairy sheep breeds (Churra and Castellana) to ascertain the initial status of protection against scrapie as a first step toward adapting their breeding schemes to include resistance as a complementary selection criterion. The procedure for genotype identification is based on multiplex minisequencing methodology and has been shown to be accurate, easy to interpret, and to have a medium throughput. The frequency of the ARQ allele was similar in the 2 populations at nearly 70%. The ARR allele, associated with resistance in the homozygous state, reaches around 23% in Churras and nearly 20% in Castellanas. The high-risk VRQ allele appeared at a relatively low frequency in both breeds. No other haplotypes were found in these 2 breeds. Furthermore, in this screening we found a new allele carrying leucine at codon 154. This new genetic variant might play a role in susceptibility to scrapie because codon 154 belongs to a region considered to have an important role in conformational conversion of the cellular to the pathogenic protein.