title: Protective effect of the AT137RQ and ARQK176 PrP allele against classical scrapie in Sarda breed sheep.
abstract: The susceptibility of sheep to scrapie is under the control of the host's prion protein (PrP gene and is also influenced by the strain of the agent. PrP polymorphisms at codons 136 (A/V), 15 (R/H) and 171 (Q/R/H) are the main determinants of susceptibility/resistance of sheep to classical scrapie. They are combined in four main variants of the wild-type ARQ allele: VRQ, AHQ, ARH and ARR. Breeding programmes have been undertaken on this basis in the European Union and th USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report th results of a multi-flock study showing the protective effect of polymorphisms other than those a codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 37 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the Pr gene. The distribution of variations other than those at the standard three codons, between scrapie cases and negative controls, was statistically different in all flocks. In particular, the AT(137)RQ an ARQK(176) alleles showed a clear protective effect. This is the first study demonstrating a protective influence of alleles other than ARR under field conditions. If further investigations in other sheep breeds and with other scrapie sources confirm these findings, the availability of various protective alleles in breeding programmes of sheep for scrapie resistance could be useful in breeds with a low frequency of the ARR allele and would allow maintaining a wider variability of the PrP gene.
authors.affiliation: Istituto Superiore di Sanità, 00161 Rome, Italy. gabriele.vaccari@iss.it
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vaccari
authors.forename: Gaia
authors.initials: G
authors.lastname: Scavia
authors.forename: Marcello
authors.initials: M
authors.lastname: Sala
authors.forename: Gianmario
authors.initials: G
authors.lastname: Cosseddu
authors.forename: Barbara
authors.initials: B
authors.lastname: Chiappini
authors.forename: Michela
authors.initials: M
authors.lastname: Conte
authors.forename: Elena
authors.initials: E
authors.lastname: Esposito
authors.forename: Raniero
authors.initials: R
authors.lastname: Lorenzetti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Perfetti
authors.forename: Paola
authors.initials: P
authors.lastname: Marconi
authors.forename: Francesco
authors.initials: F
authors.lastname: Scholl
authors.forename: Katia
authors.initials: K
authors.lastname: Barbaro
authors.forename: Antonino
authors.initials: A
authors.lastname: Bella
authors.forename: Romolo
authors.initials: R
authors.lastname: Nonno
authors.forename: Umberto
authors.initials: U
authors.lastname: Agrimi
mesh_terms: D000483:Alleles; D000818:Animals; D004196:Disease Outbreaks / Q000662:veterinary; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007558:Italy / Q000453:epidemiology; D012608:Scrapie / Q000235:genetics*; D012756:Sheep