Protective effect of the AT137RQ and ARQK176 PrP alleles against classical scrapie in Sarda breed sheep

Gabriele Vaccari , Gaia Scavia , Marcello Sala , Gianmario Cosseddu , Barbara Chiappini , Michela Conte , Elena Esposito , Raniero Lorenzetti , Gabriella Perfetti , Paola Marconi , Francesco Scholl , Katia Barbaro , Antonino Bella , Romolo Nonno , Umberto Agrimi

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), 154 (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 the USA to increase the frequency of the resistant ARR allele in sheep populations. Herein, we report the results of a multi-flock study showing the protective effect of polymorphisms other than those at codons 136, 154 and 171 in Sarda breed sheep. All ARQ/ARQ affected sheep (n = 154) and 378 negative ARQ/ARQ controls from four scrapie outbreaks were submitted to sequencing of the PrP 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 AT137RQ and ARQK176 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.

Mots clés: transmissible spongiform encephalopathy; PrP; genetics; scrapie; sheep

Domaines: Biologie moléculaire; Génétique animale; Biologie cellulaire; Interactions cellulaires [q-bio.CB]; Microbiologie et Parasitologie; Immunologie; Neurosciences [q-bio.NC]; Santé publique et épidémiologie; Biologie animale

Gabriele Vaccari, Gaia Scavia, Marcello Sala, Gianmario Cosseddu, Barbara Chiappini, et al.. Protective effect of the AT137RQ and ARQK176 PrP alleles against classical scrapie in Sarda breed sheep. Veterinary Research, 2009, 40 (3), ⟨10.1051/vetres:2009002⟩. ⟨hal-00903082⟩