title: 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.
abstract: 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.
authors.affiliation: INRA, UR 631, Station d'amélioration génétique des animaux, BP 52627, 31326 Castanet-Tolosan Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Barillet
authors.affiliation: INRA, UR 339, Laboratoire de génétique biochimique et cytogénétique, 78352 Jouy-en-Josas Cedex, France.
authors.forename: D
authors.initials: D
authors.lastname: Mariat
authors.affiliation: GIE Labogena, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Amigues
authors.affiliation: GIE Labogena, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
authors.forename: R
authors.initials: R
authors.lastname: Faugeras
authors.affiliation: INRA, UR 631, Station d'amélioration génétique des animaux, BP 52627, 31326 Castanet-Tolosan Cedex, France.
authors.forename: H
authors.initials: H
authors.lastname: Caillat
authors.affiliation: INRA, UR 339, Laboratoire de génétique biochimique et cytogénétique, 78352 Jouy-en-Josas Cedex, France.
authors.forename: K
authors.initials: K
authors.lastname: Moazami-Goudarzi
authors.affiliation: INRA, UR 631, Station d'amélioration génétique des animaux, BP 52627, 31326 Castanet-Tolosan Cedex, France.
authors.forename: R
authors.initials: R
authors.lastname: Rupp
authors.affiliation: GIE Labogena, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Babilliot
authors.affiliation: INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Lacroux
authors.affiliation: INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Lugan
authors.affiliation: INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Schelcher
authors.affiliation: AFSSA-Niort, Laboratoire d'études et de recherches caprines, BP 3081, 79012 Niort Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Chartier
authors.affiliation: INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
authors.forename: F
authors.initials: F
authors.lastname: Corbière
authors.affiliation: INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France.
authors.forename: O
authors.initials: O
authors.lastname: Andréoletti
authors.affiliation: AFSSA-Niort, Laboratoire d'études et de recherches caprines, BP 3081, 79012 Niort Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Perrin-Chauvineau
mesh_terms: D000483:Alleles; D000818:Animals; D003062:Codon / Q000235:genetics*; D005602:France; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015511:Goat Diseases / Q000235:genetics / Q000378:metabolism; D006041:Goats / Q000145:classification / Q000378:metabolism*; D006239:Haplotypes; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics*; D012608:Scrapie / Q000235:genetics / Q000378:metabolism
chemical_list: D003062:Codon; D011328:Prions