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Journal of General Virology (1999), 80, 2527-2534.
© 1999 Society for General Microbiology

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PrP gene polymorphism and natural scrapie in Icelandic sheep

Stefania Thorgeirsdottir1, Sigurdur Sigurdarson1, Hjalti Mar Thorisson1, Gudmundur Georgsson1 and Astridur Palsdottir1

Institute for Experimental Pathology, University of Iceland, Keldur, IS-112 Reykjavík, Iceland1

Author for correspondence: Astridur Palsdottir.Fax +354 5673979. e-mail astripal{at}rhi.hi.is

The association between scrapie and polymorphism of the prion protein (PrP) gene was studied in the Icelandic sheep breed. Polymorphism of the three codons, 136, 154 and 171, that are important for scrapie susceptibility was determined. A BspHI restriction analysis was used to study the alleles of codons 136 and 154, while density gradient gel electrophoresis (DGGE) was used to analyse codon 171 and detect new polymorphisms. The PrP allelic variant, VRQ (amino acids at codons 136, 154 and 171), was found to be highly statistically associated with scrapie, whereas the allelic variant, AHQ, was never found in scrapie-affected animals, a finding that is statistically significant. Iceland has a few scrapie-free regions, which are a part of a quarantine network. Homozygotes for the VRQ variant were found there at a low frequency, indicating that genetic susceptibility is not enough for scrapie to develop and further evidence for the infectious nature of the disease. A comparison of PrP genotypes between sheep outside and within the scrapie-free zones revealed an increase in the AHQ allelic variant in the latter. No polymorphism was found at codon 171 in a total of 932 sheep studied, all individuals having the glutamine allele. Two novel, rare PrP alleles were found using DGGE at codons 138 and 151, i.e. S138N and R151C. Their relevance to scrapie is still unclear, but the former was found in scrapie-affected sheep as well as healthy sheep, whereas the latter was only found in healthy sheep.




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