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1 National Reference Centre for Transmissible Spongiform Encephalopathies, Animal Pathology Department, Veterinary Faculty, C/Miguel Servet 177, 50013 Zaragoza, Spain
2 Biochemical Genetics and Blood Groups Laboratory, University of Zaragoza, C/Miguel Servet 177, 50013 Zaragoza, Spain
3 Institute for Animal Health, Neuropathogenesis Unit, West Mains Road, Edinburgh EH9 3JF, UK
Correspondence
Cristina Acín
crisacin{at}unizar.es
The Rasa Aragonesa sheep is the second most important Spanish breed after the Merino breed. Reported here is the prion protein (PrP) haplotype frequency distribution for scrapie-related codons (136, 154 and 171) and a sequencing study of the complete PrP gene open reading frame for this breed and six other closely related breeds. The study includes four scrapie-affected sheep flocks belonging to Rasa Aragonesa and Rasa Navarra breeds. Thirty-eight scrapie-affected sheep, 502 healthy sheep from scrapie-affected flocks and 905 sheep from a breed survey were genotyped. The most frequent PrP haplotype in both scrapie and healthy flocks was ARQ, which was found at significantly higher frequency in scrapie-affected sheep. The susceptibility-associated VRQ haplotype was found at low frequencies in six out of eight breeds, but was not present in the 38 scrapie-affected sheep. The resistance-associated ARR haplotype was found in all breeds except one (Ojinegra) at frequencies 
14 %. Fourteen amino acid polymorphisms were detected in these Spanish sheep, including the known amino acid substitutions at codons 112, 136, 141, 143, 154, 171 and 176, and new polymorphisms at codons 101 (Q
R), 151 (RG), 151 (RH), 172 (YD) and 175 (QE). Most of the novel polymorphic codons show frequencies lower than 5 %.
These authors contributed equally to this work.
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