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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

¹ INRA, UR 631, Station d'amélioration génétique des animaux, BP 52627, 31326 Castanet-Tolosan Cedex, France
² INRA, UR 339, Laboratoire de génétique biochimique et cytogénétique, 78352 Jouy-en-Josas Cedex, France
³ GIE Labogena, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France
⁴ INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France
⁵ AFSSA-Niort, Laboratoire d'études et de recherches caprines, BP 3081, 79012 Niort Cedex, France

Correspondence
F. Barillet
francis.barillet{at}toulouse.inra.fr

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 (GIH₁₅₄RQS, GIRQ₂₁₁QS, GIRRK₂₂₂S and GIRRQP₂₄₀) derived from the wild-type allele (G₁₂₇I₁₄₂R₁₅₄R₂₁₁Q₂₂₂S₂₄₀) by a single-codon mutation, and two (S₁₂₇IRRQP₂₄₀ and GM₁₄₂RRQP₂₄₀) 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 I₁₄₂R₁₅₄R₂₁₁Q₂₂₂/IRRQ goats, the odds of scrapie cases in IRQ₂₁₁Q/IRRQ and IRRK₂₂₂/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, P<0.0001; and OR=0.048, P<0.0001, respectively]. The heterozygote M₁₄₂RRQ/IRRQ genotype was only protective (OR=0.243, P=0.0186) in goats also PP₂₄₀ 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.

A supplementary table is available with the online version of this paper.