Abstract
To determine whether an association between specific combinations of polymorphisms in the PrP gene of sheep and natural scrapie exists, we applied denaturing gradient gel electrophoresis (DGGE) to analyze the PrP genes of 69 scrapie-affected and 176 healthy sheep predominantly of the Texel breed. We found six PrP allelic variants representing different combinations of polymorphisms at codons 136, 154, 171, and 211. Based on the triplet sequences present at codons 136, 154, and 171, these alleles were designated PrPVRQ, PrPARR, PrPARQ, PrPARH, PrPAHQ, and PrPARQQ211. Among the 245 sheep, 15 different PrP genotypes or allele pairs were present. The distribution of the allelic variants revealed that the PrPVRQ allele is associated with a high incidence of natural scrapie and the PrPARR allele with a low incidence. The PrPARQ and PrPARH alleles were not associated with disease incidence. Nevertheless, a number of scrapie-affected sheep were homozygous for the PrPARQ allele. Whether in these sheep factors other than the PrP genotype play a more decisive role in inducing the disease than in sheep with a PrPVRQ allele remains to be established. The frequencies of the PrPAHQ and the PrPARQQ211 alleles were too low to draw any conclusions.
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References
Parry HB. Scrapie: a transmissible and hereditary disease of sheep. Heredity 1962;17:75–105.
Dickinson AG, Young GB, Stamp JT, Renwick CC. An analysis of natural scrapie in Suffolk sheep. Heredity 1965;20:485–503.
Brotherston JG, Renwick CC, Stamp JT, Zlotnick I. Spread of scrapie by contact to goats and sheep. J Comp Pathol 1968;78:9–17
Dickinson AG, Stamp JT, Renwick CC. Maternal and lateral transmission of scrapie in sheep. J Comp Pathol 1974;84:19–25.
Dickinson AG, Outram GW. Genetic aspects of unconventional virus infections: the basis of the virino hypothesis. In: Bock G, Marsh J, eds. Novel infectious agents of the central nervous system. Ciba Foundation Symposium. London: Wiley-Interscience, 1988;135:63–83.
Prusiner SB. Molecular biology of prion diseases. Science 1991;252:1515–1522.
Prusiner SB. Genetic and infectious prion’s diseases. Arch Neurol 1993; 50:1129–1153.
Collinge J, Palmer MS, Dryden AJ. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 1991;337:1441–1442.
Palmer MS, Dryden AJ, Hughes JT, Collinge J. Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature 1991; 352:340–342.
Goldfarb LG, Petersen RB, Tabaton M, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science 1992;258:806–808.
Goldmann W, Hunter N, Foster JD, Salbaum JM, Beyreuther K, Hope J. Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci USA 1990;87:2476–2480.
Goldmann W, Hunter N, Benson G, Foster JD, Hope J. Different scrapie-associated fibril proteins (PrP) are encoded by lines of sheep selected for different alleles of the Sip gene. J Gen Virol 1991;72:2411–2417.
Laplanche JL, Chatelain J, Westaway D, et al. PrP polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis. Genomics 1993;15:30–37.
Goldmann W, Hunter N, Smith G, Foster J, Hope J. PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. J Gen Virol 1994;75:989–995.
Maciulis A, Hunter N, Wang S, Goldmann W, Hope J, Foote W. Polymorphisms of a scrapie-associated fibril protein (PrP) gene and their association with susceptibility to experimentally induced scrapie in Cheviot sheep in the United States. Am J Vet Res 1992;53:1957–1960.
Hunter N, Goldmann W, Benson G, Foster JD, Hope J. Swaledale sheep affected by natural scrapie differ significantly in PrP genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie. J Gen Virol 1993;74:1025–1031.
Westaway D, Zuliani V, Cooper CM, et al. Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev 1994;8:959–969.
Van Keulen LJM, Schreuder BEC, Meloen RH, et al. Immunohistochemical detection and localization of prion protein in brain tissue of sheep with natural scrapie. Vet Pathol 1995;32:299–308.
Schreuder BEC, De Jong MCM, Pekelder JJ, Vellema P, Bröker AJM, Betcke H. Prevalence and incidence of scrapie in the Netherlands: a questionnaire survey. Vet Rec 1993;133:211–214.
Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. 2nd ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1989.
Belt PBGM, Muileman IH, Schreuder BEC, Bos-de Ruijter J, Gielkens ALJ, Smits MA. Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. J Gen Virol 1995;76:509–517.
Myers RM, Maniatis T, Lerman LS. Detection and localization of single bases changes by denaturing gradient gel electrophoresis. In: Wu R, ed. Methods Enzymol 1987;155:501–527.
Sanger F, Niklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;74:5463–5467.
Hsiao K, Scott M, Foster D, Groth D, Dearmond S, Prusiner S. Spontaneous neurodegeneration in transgenic mice with mutant prion protein of Gerstmann-Sträussler syndrome. Science 1990;250:1587–1590.
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Belt, P.B.G.M., Bossers, A., Schreuder, B.E.C., Smits, M.A. (1996). PrP Allelic Variants Associated with Natural Scrapie. In: Gibbs, C.J. (eds) Bovine Spongiform Encephalopathy. Serono Symposia USA Norwell, Massachusetts. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2406-8_21
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DOI: https://doi.org/10.1007/978-1-4612-2406-8_21
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