|Knowles, Donald - Don|
Submitted to: Gene
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/27/2003
Publication Date: 12/5/2003
Citation: Brayton, K.A., O'Rourke, K.I., Lyda, A.K., Miller, M.W., Knowles, D.P. A processed pseudogene contributes to apparent mule deer prion gene heterogeneity. Gene. 2003. v. 326. p. 167-173. Interpretive Summary: Chronic wasting disease is a prion disorder of deer and elk. Efforts to control disease in free ranging and farmed populations are often limited to destruction of infected and exposed animals. Resistance to the related disorder in sheep is associated with changes in the PRNP gene. Investigation of the PRNP gene of mule deer with CWD revealed the presence of a normal gene and a duplicated, nonfunctional copy. This pseudogene is not expected to affect disease susceptibility but complicates genetic studies of mule deer because of its similarity to the normal gene. Selection of genotyping methods specific for the normal gene and the pseudogene are necessary for the large scale studies needed to determine whether CWD-resistance occurs in the mule deer population.
Technical Abstract: The ruminant transmissible spongiform encephalopathies (TSEs) are a heterogeneous group of fatal neurodegenerative disorders affecting cattle, sheep, goats, deer and elk. The TSE of mule deer, chronic wasting disease (CWD), was reported in the 1980s in a small region of Colorado. The disease is now reported in white tailed deer and elk in several areas of the US and Canada. CWD is the subject of aggressive control programs, including depopulation of affected captive and free ranging groups. Ovine scrapie, the related TSE of sheep, is controlled by host genetics. Polymorphisms in the PRNP gene are associated with relative disease resistance in many breeds of sheep and scrapie losses can be prevented through selective breeding programs. Under field conditions, alleles associated with relative susceptibility are identified by DNA sequence analysis of the open reading frame of the PRNP gene in affected animals. In this study, sequence analysis of the PRNP gene from mule deer showed polymorphisms at specific sites in the gene from more than 99% of the animals tested. Individual deer were shown to have more than 2 alleles, demonstrating that the gene had been duplicated. A bacterial artificial chromosome library of mule deer DNA was constructed and screened for exon 1 of the PRNP gene. Analysis of the clones revealed a full length functional gene and a processed pseudogene with characteristics of previously described retrotransposons. cDNA analysis indicated that the pseudogene was not expressed. Several alleles of the pseudogene were identified in the target population. Because susceptibility to the TSEs depends on the presence of the native prion protein, an untranslated pseudogene is not expected to affect disease resistance. However, selection of genotyping methods specific for the functional gene is critical for large scale studies to identify the role of the PRNP gene in susceptibility to CWD in mule deer.