Polymorphisms of Codons 110, 146, 211 and 222 at the Goat PRNP Locus and Their Association with Scrapie in Greece

SIMPLE SUMMARY: Scrapie is a transmissible spongiform encephalopathy affecting sheep and goats. Due to similarities with mad cow disease (BSE) which is transmissible to humans, scrapie is considered of significance for its theoretical zoonotic potential. A variety of control strategies have been proposed and applied over the years. While herd depopulation, culling of affected susceptible animals, and disinfection measures are poorly successful, selective breeding schemes focused on amino acid substitutions (polymorphisms) in prion protein (PrP) would be the best way for eradication. In sheep, the association between PrP gene polymorphism argininine on codon 171 is highly effective for scrapie resistance breeding. Although in goats this polymorphism is absent, three other candidate PrP amino acid polymorphisms have been recognized for resistance breeding. For Greece with the largest goat population in Europe, the frequencies of these polymorphisms has yet to be sufficiently documented. This study performed a large-scale, cross-sectional survey for a large part of the country, regarding PrP polymorphic codons 110, 146, 211, and 222, and estimated effects of these polymorphisms on (i) the likelihood to be infected by scrapie, and (ii) scrapie status at the herd level, revealing possible candidate PrP amino acid polymorphisms to be used in breeding for scrapie-resistance programs. ABSTRACT: Scrapie is considered an endemic disease in both sheep and goats in Greece. However, contrary to sheep, in goats more than one prion protein (PrP) polymorphism has been recognized as a candidate for resistance breeding against the disease. For an impression, candidates which are circulating, (i) brain samples (n = 525) from scrapie-affected (n = 282) and non-affected (n = 243) animals within the national surveillance program, and (ii) individual blood samples (n = 1708) from affected (n = 241) and non-affected (n = 1467) herds, in a large part of mainland Greece and its islands, were collected and assayed. A dedicated Taqman method was used to test for amino acid polymorphisms 110T/P, 146N/S/D, 211R/Q, and 222Q/K. Highly prevalent genotypes were 110TT, 146NN, 211RR, and 222QQ. The frequencies of polymorphisms in blood and negative brain samples for codons 110P, 211Q, and 222K were 4.0%, 3.0%, and 1.9%, respectively, while 146D (0.7%) was present only on Karpathos island. Codon 110P was exclusively found in scrapie-negative brains, and homozygous 110P/P in two scrapie-negative goats. It is concluded that breeding programs in Karpathos could focus on codon 146D, while in other regions carriers of the 110P and 222K allele should be sought. Case-control and challenge studies are now necessary to elucidate the most efficient breeding strategies.