Prion gene (PRNP) haplotype variation in United States goat breeds(Open Access publication)

Abstract

-Scrapie eradication efforts cost 18 million dollars annually in the United States and rely heavily upon PRNP genotyping of sheep. Genetic resistance might reduce goat scrapie and limit the risk of goats serving as a scrapie reservoir, so PRNP coding sequences were examined from 446 goats of 10 breeds, 8 of which had not been previously examined at PRNP. The 10 observed alleles were all related to one of two central haplotypes by a single amino acid substitution. At least five of these alleles (M142, R143, S146, H154, and K222) have been associated with increased incubation time or decreased odds of scrapie. To the best of our knowledge, neither S146 nor K222 has been found in any goats with scrapie, though further evaluation will be required to demonstrate true resistance. S146 was more common, present in several breeds at widely varying frequencies, while K222 was observed only in two dairy breeds at low frequency. Overall, this study provides frequency data on PRNP alleles in US goats, shows the pattern of relationships between haplotypes, and demonstrates segregation of multiple scrapieassociated alleles in several breeds not examined before at PRNP. scrapie / goat / polymorphism / resistance / prion

State-of-the-art review of goat TSE in the European Union, with special emphasis onPRNPgenetics and epidemiology

“…I). In breeds and populations from outside Europe, these and a few novel PRNP polymorphisms have been described: (China) W102G (indicating the wild-type amino acid, the codon and the variant observed), G127S, H143R, N146S, R154H, R211G, R211Q, I218L, T219I, Q222K, S240P [75, 76]; (Japan) W102G, G127S, I142M, H143R, N146S, R211Q, S240P [45]; (Pakistan) S240P [5]; and (USA) G127S, I142M, H143R, N146S, R154H, R211Q, Q222K, S240P [70]. Summarising Table I, it appears that many of the amino acid polymorphisms occur as yet in only one or two countries.…”

“…The other haplotypes generally seem to have arisen by mutations on the background of these two central haplotypes, relating to one or the other by a single amino acid substitution. Exceptions are haplotypes M142-S240, M142-P240 and H154-S240, H152-P240 [1, 6, 10, 33, 70]. Furthermore, two haplotypes with a double mutation (V37-K222 and H154-K222) have been reported [18, 66].…”

“…Studies on PRNP haplotype frequencies in goats in Italy, France, the USA, Japan and China [6, 18, 45, 70, 76] have been published so far. The currently observed frequency range (in % of all alleles) reported for the variant haplotyopes associated with partial resistance to scrapie are summarized in Table II.…”

Transmissibility of caprine scrapie in ovine transgenic mice

“…This genotype is identified in more than 90% of the scrapie cases diagnosed in the US [10] and Canada [11]. The caprine PRNP gene is highly polymorphic [12,13] and there is no standard nomenclature for naming alleles. Polymorphisms have been identified on two haplotypes, differing at codon 240 (encoding proline P or serine S).…”

“…Diploid PRNP genotypes were determined by polymerase chain reaction amplification of the open reading frame followed by DNA sequence analysis of both strands using standard methods [12,42]. …”