1887

Abstract

The primary sequence of the prion protein affects susceptibility to transmissible spongiform encephalopathies, or prion diseases, in mice, sheep and humans. The gene sequence of free-ranging, Wisconsin white-tailed deer was determined and the genotypes of chronic wasting disease (CWD)-positive and CWD-negative deer were compared. Six amino acid changes were identified, two of which were located in pseudogenes. Two alleles, a Q→K polymorphism at codon 226 and a single octapeptide repeat insertion into the pseudogene, have not been reported previously. The predominant alleles – wild-type (Q95, G96 and Q226) and a G96S polymorphism – comprised almost 98 % of the alleles in the Wisconsin white-tailed deer population. Comparison of the allelic frequencies in the CWD-positive and CWD-negative deer suggested that G96S and a Q95H polymorphism were linked to a reduced susceptibility to CWD. The G96S allele did not, however, provide complete resistance, as a CWD-positive G96S/G96S deer was identified. The G96S allele was also linked to slower progression of the disease in CWD-positive deer based on the deposition of PrP in the obex region of the medulla oblongata. Although the reduced susceptibility of deer with at least one copy of the Q95H or G96S allele is insufficient to serve as a genetic barrier, the presence of these alleles may modulate the impact of CWD on white-tailed deer populations.

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2006-07-01
2024-03-28
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References

  1. Bartz J. C., Aiken J. M., Bessen R. A. 2004; Delay in onset of prion disease for the HY strain of transmissible mink encephalopathy as a result of prior peripheral inoculation with the replication-deficient DY strain. J Gen Virol 85:265–273 [CrossRef]
    [Google Scholar]
  2. Bessen R. A., Kocisko D. A., Raymond G. J., Nandan S., Lansbury P. T., Caughey B. 1995; Non-genetic propagation of strain-specific phenotypes of scrapie prion protein. Nature 375:698–700 [CrossRef]
    [Google Scholar]
  3. Brayton K. A., O'Rourke K. I., Lyda A. K., Miller M. W., Knowles D. P. 2004; A processed pseudogene contributes to apparent mule deer prion gene heterogeneity. Gene 326:167–173 [CrossRef]
    [Google Scholar]
  4. Dickinson A. G., Meikle V. M., Fraser H. 1968; Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. J Comp Pathol 78:293–299 [CrossRef]
    [Google Scholar]
  5. Hamir A. N., Gidlewski T., Spraker T. R., Miller J. M., Creekmore L., Crocheck M. Cline T., O'Rourke K. I. 2006; Preliminary observations of genetic susceptibility of elk ( Cervus elaphus nelsoni ) to chronic wasting disease by experimental oral inoculation. J Vet Diagn Invest 18:110–114 [CrossRef]
    [Google Scholar]
  6. 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]
  7. Iniguez V., McKenzie D., Mirwald J., Aiken J. M. 2000; Strain-specific propagation of PrPSc properties into baculovirus-expressed PrPC . J Gen Virol 81:2565–2571
    [Google Scholar]
  8. Jewell J. E., Conner M. M., Wolfe L. L., Miller M. W., Williams E. S. 2005; Low frequency of PrP genotype 225SF among free-ranging mule deer ( Odocoileus hemionus ) with chronic wasting disease. J Gen Virol 86:2127–2134 [CrossRef]
    [Google Scholar]
  9. Johnson C., Johnson J., Clayton M., McKenzie D., Aiken J. 2003; Prion protein gene heterogeneity in free-ranging white-tailed deer within the chronic wasting disease affected region of Wisconsin. J Wildl Dis 39:576–581 [CrossRef]
    [Google Scholar]
  10. O'Rourke K. I., Besser T. E., Miller M. W., Cline T. F., Spraker T. R., Jenny A. L., Wild M. A., Zebarth G. L., Williams E. S. 1999; PrP genotypes of captive and free-ranging Rocky Mountain elk ( Cervus elaphus nelsoni ) with chronic wasting disease. J Gen Virol 80:2765–2769
    [Google Scholar]
  11. O'Rourke K. I., Spraker T. R., Hamburg L. K., Besser T. E., Brayton K. A., Knowles D. P. 2004; Polymorphisms in the prion precursor functional gene but not the pseudogene are associated with susceptibility to chronic wasting disease in white-tailed deer. J Gen Virol 85:1339–1346 [CrossRef]
    [Google Scholar]
  12. Prusiner S. B., Scott M. R. 1997; Genetics of prions. Annu Rev Genet 31:139–175 [CrossRef]
    [Google Scholar]
  13. Raymond G. J., Bossers A., Raymond L. D. & 7 other authors 2000; Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J 19:4425–4430 [CrossRef]
    [Google Scholar]
  14. Spraker T. R., Zink R. R., Cummings B. A., Sigurdson C. J., Miller M. W., O'Rourke K. I. 2002; Distribution of protease-resistant prion protein and spongiform encephalopathy in free-ranging mule deer ( Odocoileus hemionus ) with chronic wasting disease. Vet Pathol 39:546–556 [CrossRef]
    [Google Scholar]
  15. Tranulis M. A. 2002; Influence of the prion protein gene, Prnp , on scrapie susceptibility in sheep. APMIS 110:33–43 [CrossRef]
    [Google Scholar]
  16. Westaway D., Goodman P. A., Mirenda C. A., McKinley M. P., Carlson G. A., Prusiner S. B. 1987; Distinct prion proteins in short and long scrapie incubation period mice. Cell 51:651–662 [CrossRef]
    [Google Scholar]
  17. Zhang Z., Gurr S. J. 2000; Walking into the unknown: a ‘step down’ PCR-based technique leading to the direct sequence analysis of flanking genomic DNA. Gene 253:145–150 [CrossRef]
    [Google Scholar]
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