A processed pseudogene contributes to apparent mule deer prion gene heterogeneity.

Area of Science:

• Genetics
• Neuroscience
• Veterinary Medicine

Background:

• Prion disorders, or transmissible spongiform encephalopathies (TSEs), are caused by abnormal prion protein (PrP) isoforms.
• Susceptibility to TSEs is influenced by variations in the prion protein gene (PRNP) in various species.
• Mule deer are susceptible to chronic wasting disease (CWD), a significant TSE, but their PRNP genetics remain uncharacterized.

Purpose of the Study:

• To investigate the prion protein gene (PRNP) polymorphisms and alleles in mule deer.
• To identify potential genetic factors influencing susceptibility to chronic wasting disease (CWD) in mule deer.
• To differentiate between functional PRNP genes and pseudogenes for accurate genetic analysis.

Main Methods:

• Analysis of the open reading frame (ORF) in exon 3 of the mule deer PRNP gene.
• Identification and characterization of PRNP genes and pseudogenes using BAC clones.
• Genotyping of PRNP functional gene alleles in both CWD-positive and general mule deer populations.

Main Results:

• Multiple PRNP polymorphisms were identified in mule deer, including a common heterozygous coding change at codon 138.
• A functional PRNP gene and a processed pseudogene were discovered, with three alleles identified for the functional gene.
• The 20D225S allele was predominant in CWD-positive mule deer (frequency 0.85).
• Three pseudogene alleles were also identified, but are not expected to influence disease resistance.

Conclusions:

• Mule deer possess a functional PRNP gene and a pseudogene, with specific functional gene alleles associated with CWD.
• Accurate genotyping methods focusing on the functional PRNP gene are crucial for future studies on CWD susceptibility in mule deer.
• Understanding PRNP genetics is vital for managing and mitigating CWD in susceptible wildlife populations.