1887

Abstract

Great Britain and elsewhere have detected atypical scrapie infection in sheep with PrP genotypes thought to be genetically resistant to the classical form of scrapie. DNA sequencing of the PrP gene of British atypical scrapie cases (=69), classical scrapie cases (=59) and scrapie-free controls (=138) was undertaken to identify whether PrP variants, other than the three well-characterized polymorphic codons, influenced susceptibility to atypical scrapie infection. Four non-synonymous changes, M112T, M137T, L141F and P241S, were detected that are most probably associated with the ARQ haplotype. Only the PrP variant containing a phenylalanine residue at amino acid position 141 was found to be associated more commonly with the atypical scrapie cases. In addition to the single nucleotide polymorphisms associated with the ARQ allele, two out of nine atypical scrapie cases with the ARR/ARR genotype were found to contain a 24 bp insertion, leading to an additional octapeptide repeat. In terms of PrP genetics, one classification of the GB scrapie cases examined in this study would place animals carrying any homozygous or heterozygous combination of ARR, AHQ or AFRQ alleles, or any one of these alleles when paired with ARQ, as being susceptible to atypical scrapie infection, and animals heterozygous or homozygous for VRQ or homozygous for ARQ as being susceptible to classical scrapie disease. The AHQ PrP allele was associated with the highest incidence of atypical scrapie (263 per 100 000 alleles), whilst VRQ was associated with the lowest incidence (10 per 100 000 alleles).

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2006-11-01
2024-04-18
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References

  1. Anonymous. 2005; Opinion of the Scientific Panel on Biological Hazards on the request from the European Commission on classification of atypical transmissible spongiform encephalopathy (TSE) cases in small ruminants. EFSA J 276:1–30
    [Google Scholar]
  2. Baylis M., Goldmann W. 2004; The genetics of scrapie in sheep and goats. Curr Mol Med 4:385–396 [CrossRef]
    [Google Scholar]
  3. Baylis M., McIntyre K. M. 2004; Transmissible spongiform encephalopathies: scrapie control under new strain. Nature 432:810–811 [CrossRef]
    [Google Scholar]
  4. Baylis M., Chihota C., Stevenson E., Goldmann W., Smith A., Sivam K., Tongue S., Gravenor M. B. 2004; Risk of scrapie in British sheep of different prion protein genotype. J Gen Virol 85:2735–2740 [CrossRef]
    [Google Scholar]
  5. Benestad S. L., Sarradin P., Thu B., Schonheit J., Tranulis M. A., Bratberg B. 2003; Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153:202–208 [CrossRef]
    [Google Scholar]
  6. Buschmann A., Lühken G., Schultz J., Erhardt G., Groschup M. H. 2004a; Neuronal accumulation of abnormal prion protein in sheep carrying a scrapie-resistant genotype (PrPARR/ARR). J Gen Virol 85:2727–2733 [CrossRef]
    [Google Scholar]
  7. Buschmann A., Biacabe A.-G., Ziegler U., Bencsik A., Madec J.-Y., Erhardt G., Lühken G., Baron T., Groschup M. H. 2004b; Atypical scrapie cases in Germany and France are identified by discrepant reaction patterns in BSE rapid tests. J Virol Methods 117:27–36 [CrossRef]
    [Google Scholar]
  8. Dawson M., Hoinville L. J., Hosie B. D., Hunter N. 1998; Guidance on the use of PrP genotyping as an aid to the control of clinical scrapie. Scrapie Information Group. Vet Rec 142:623–625
    [Google Scholar]
  9. De Bosschere H., Roels S., Benestad S. L., Vanopdenbosch E. 2004; Scrapie case similar to Nor98 diagnosed in Belgium via active surveillance. Vet Rec 155:707–708 [CrossRef]
    [Google Scholar]
  10. Everest S. J., Thorne L., Barnicle D. A., Edwards J. C., Elliott H., Jackman R., Hope J. 2006; Atypical prion protein in sheep brain collected during the British scrapie-surveillance programme. J Gen Virol 87:471–477 [CrossRef]
    [Google Scholar]
  11. Gavier-Widen D., Nöremark M., Benestad S., Simmons M., Renström L., Bratberg B., Elvander M., af Segerstad C. H. 2004; Recognition of the Nor98 variant of scrapie in the Swedish sheep population. J Vet Diagn Invest 16:562–567 [CrossRef]
    [Google Scholar]
  12. Goldmann W., Hunter N., Smith G., Foster J., Hope J. 1994; 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 75:989–995 [CrossRef]
    [Google Scholar]
  13. Goldmann W., Baylis M., Chihota C., Stevenson E., Hunter N. 2005; Frequencies of PrP gene haplotypes in British sheep flocks and the implications for breeding programmes. J Appl Microbiol 98:1294–1302 [CrossRef]
    [Google Scholar]
  14. Heaton M. P., Leymaster K. A., Freking B. A. & 7 other authors 2003; Prion gene sequence variation within diverse groups of U.S. sheep, beef cattle, and deer. Mamm Genome 14:765–777 [CrossRef]
    [Google Scholar]
  15. Houston F., Goldmann W., Chong A., Jeffrey M., González L., Foster J., Parnham D., Hunter N. 2003; Prion diseases: BSE in sheep bred for resistance to infection. Nature 423:498 [CrossRef]
    [Google Scholar]
  16. Ikeda T., Horiuchi M., Ishiguro N., Muramatsu Y., Kai-Uwe G. D., Shinagawa M. 1995; Amino acid polymorphisms of PrP with reference to onset of scrapie in Suffolk and Corriedale sheep in Japan. J Gen Virol 76:2577–2581 [CrossRef]
    [Google Scholar]
  17. Lee I. Y., Westaway D., Smit A. F. A. & 10 other authors 1998; Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res 8:1022–1037
    [Google Scholar]
  18. Lühken G., Buschmann A., Groschup M. H., Erhardt G. 2004; Prion protein allele A 136 H 154 Q 171 is associated with high susceptibility to scrapie in purebred and crossbred German Merinoland sheep. Arch Virol 149:1571–1580
    [Google Scholar]
  19. Madec J.-Y., Simon S., Lezmi S., Bencsik A., Grassi J., Baron T. 2004; Abnormal prion protein in genetically resistant sheep from a scrapie-infected flock. J Gen Virol 85:3483–3486 [CrossRef]
    [Google Scholar]
  20. Moum T., Olsaker I., Hopp P., Moldal T., Valheim M., Moum T., Benestad S. L. 2005; Polymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases. J Gen Virol 86:231–235 [CrossRef]
    [Google Scholar]
  21. Onnasch H., Gunn H. M., Bradshaw B. J., Benestad S. L., Bassett H. F. 2004; Two Irish cases of scrapie resembling Nor98. Vet Rec 155:636–637 [CrossRef]
    [Google Scholar]
  22. Orge L., Galo A., Machado C., Lima C., Ochoa C., Silva J., Ramos M., Simas J. P. 2004; Identification of putative atypical scrapie in sheep in Portugal. J Gen Virol 85:3487–3491 [CrossRef]
    [Google Scholar]
  23. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [CrossRef]
    [Google Scholar]
  24. Slate J. 2005; Molecular evolution of the sheep prion protein gene. Proc Biol Sci 272:2371–2377 [CrossRef]
    [Google Scholar]
  25. Wilesmith J., Matthews D., Ryan J. 2003; Summary of the results of scrapie surveillance in sheep in Great Britain; January 2002–March 2003 http://www.defra.gov.uk/animalh/bse/publications/reports/SheepSurveyRpt.pdf
  26. Wilesmith J., Ryan J., Del Rio Vilas V., Gubbins S. 2004 Summary of the results of scrapie surveillance in sheep in Great Britain: April–December; 2003 http://www.defra.gov.uk/animalh/bse/publications/reports/SheepSurvey2.pdf
    [Google Scholar]
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