title: A processed pseudogene contributes to apparent mule deer prion gene heterogeneity.
abstract: Pathogenesis and transmission of the prion disorders (transmissible spongiform encephalopathies, TSEs) are mediated by a modified isoform of the prion protein (PrP). Prion protein gene (PRNP) alleles associated with relative susceptibility to TSE have been identified in sheep, humans and possibly elk. Comparable data have not been derived for mule deer, a species susceptible to the TSE chronic wasting disease (CWD). Initial analysis of the open reading frame (ORF) in exon 3 of the mule deer PRNP gene revealed polymorphisms in all 145 samples analyzed, with 10 potential polymorphic sites. Because 144/145 (99.3%) of the samples were heterozygous for a coding change (N/S) at codon 138 (bp 412) and a non-coding polymorphism at bp 418, and individual deer with three or four different alleles were identified a possible gene duplication was indicated. Analysis of BAC clones containing mule deer PRNP genes revealed a full length functional gene and a processed pseudogene. The pseudogene was characteristic of previously described retroelements, in that it lacks introns and is flanked by repeat sequences. Three alleles of the functional gene were identified, with coding changes only at codons 20 (D/G) and 225 (S/F). Determination of PRNP functional gene alleles from 47 CWD-positive mule deer showed the predominant allele encoded 20D225S (frequency 0.85). When alleles were grouped by coding changes in the functional gene, four of the six possible peptide combinations were identified in infected deer. Three pseudogene alleles with coding changes in exon 3 were identified in the mule deer samples examined. Because the TSEs appear to be "protein only" disorders, the presence of an untranslated pseudogene is not expected to affect disease resistance. Therefore, selection of a genotyping method 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.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. kbrayton@vetmed.wsu.edu
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Brayton
authors.forename: Katherine I
authors.initials: KI
authors.lastname: O'Rourke
authors.forename: Amy K
authors.initials: AK
authors.lastname: Lyda
authors.forename: Michael W
authors.initials: MW
authors.lastname: Miller
authors.forename: Donald P
authors.initials: DP
authors.lastname: Knowles
mesh_terms: D000483:Alleles; D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D003670:Deer / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D005796:Genes / Q000235:genetics; D018740:Genetic Heterogeneity; D007438:Introns; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics*; D017422:Sequence Analysis, DNA; D034081:Wasting Disease, Chronic / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D011328:Prions; D004247:DNA