Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/23/2003
Publication Date: 4/22/2004
Citation: 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 susceptibilty to chronic wasting disease in white-tailed deer. Journal of General Virology. 85:1339-1346. Interpretive Summary: Chronic wasting disease (CWD) is a fatal brain disease of deer and elk. CWD is a member of the group of diseases associated with abnormal proteins (prions). The gene for the prion protein varies among animals and susceptibility to some prion diseases is controlled by the genetics of the host. The prion genetics of a group of white-tailed deer was examined to determine whether there was an association between the genotype and the incidence of disease. Although CWD was observed in deer of all major genotypes, deer with certain forms of the gene appeared to be somewhat less susceptible. In addition to the functional prion gene, approximately 25% of the deer also carried the cervid prion pseudogene, a defective copy of the prion gene. There was no association between the presence of the pseudogene and the incidence of CWD in this herd. Additional studies with other populations will be useful in determining the extent of the association between CWD and particular prion genotypes.
Technical Abstract: Chronic wasting disease is a transmissible spongiform encephalopathy, or prion disease, of deer and elk. Susceptibility and relative incubation time in the prion disease in sheep is controlled by polymorphisms in the ovine PRNP gene. In this study, polymorphisms of the cervid PRNP gene in a group of white-tailed deer with a high incidence of CWD were determined to evaluate the association between disease and prion genotype. Although all major genotypes were found in the CWD population, chi square analysis and odds ratio analysis, showing the 95% confidence interval, demonstrated that deer with the allele QSAS and without the allele QGAS were under-represented in the CWD population, suggesting that this genotype may be less susceptible that genotypes with the QGAS allele and lacking the QSAS allele. In addition to the functional prion gene, approximately 25% of the deer carried the previously described cervid prion pseudogene, with a complete open reading frame. Sequence analysis of deer therefore requires careful selection of primer sets to differentiate the pseudogene from the functional gene. There was no association between the pseudogene and disease in these deer. Additional studies with other populations of deer will be useful in determining the extent of the association between CWD and particular prion genotypes.