Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie

In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks ( n =404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH 154 RQS, GIRQ 211 QS, GIRRK 222 S and GIRRQP 240 ) derived from the wild-type allele (G 127 I 142 R 154 R 211 Q 222 S 240 ) by a single-codon mutation, and two (S 127 IRRQP 240 and GM 142 RRQP 240 ) by a double-codon mutation. A case–control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I 142 R 154 R 211 Q 222 /IRRQ goats, the odds of scrapie cases in IRQ 211 Q/IRRQ and IRRK 222 /IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, P <0.0001; and OR=0.048, P <0.0001, respectively]. The heterozygote M 142 RRQ/IRRQ genotype was only protective (OR=0.243, P =0.0186) in goats also PP 240 homozygous at codon 240. However, mutated allele frequencies in French Alpine and Saanen breeds were low (0.5–18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.