Prion protein polymorphisms in the white-tailed deer population influence susceptibility to chronic wasting disease

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that affects cervids. CWD was first identified in mule deer (Odocoileus hemionus), in 1967, at a research facility in Colorado. It has subsequently been detected in white-tailed deer ( Odocoileus virginianus) and elk (Cervus elaphus).; TSEs are fatal progressive neurodegenerative diseases that cause spongiform vacuolization of the brain. TSEs are typified by, if not caused by, the accumulation of the disease-associated conformation of the prion protein (PrPCWD in cervids or PrPSc as general nomenclature). PrP Sc apparently acts as a template for refolding the normal cellular PrP (PrPC) molecule, thus, differences in the primary protein sequences between PrPC and PrPSc have the potential to affect the interaction of these two molecules and the conversion process.; Detection of CWD in the Wisconsin free-ranging white-tailed deer population created a need to identify the Prnp polymorphisms and their frequencies in both the CWD-positive and CWD-negative populations. DNA sequence analysis was performed on 193 CWD-positive and 153 CWD-negative deer from within the CWD-affected region of the state as well as 183 deer from outside the affected region. Six coding polymorphisms within the 246 amino acid protein were detected, with changes at codon 95 glutamine to histidine, 96 glycine to serine, 138 serine to asparagine, 226 glutamine to lysine and a single octapeptide repeat insertion at codon 63 in an allele with the 138 codon change. The majority of deer had at least one copy of the glutamine (codon 95), glycine (codon 96) and serine (codon138) PrP allele (QGS). Approximately 98% of the PrP genes in CWD-negative white-tailed deer population are comprised of three major alleles, QGS (62.7%), QSS (25.8%) and QGN (9.2%). Deer homozygous or heterozygous for the QSS allele were significantly under-represented in the CWD-positive population compared to CWD-negative deer from the same region. In contrast, QGS homozygous and QGN heterozygous deer were both over-represented in the CWD-positive white-tailed deer population. This is the first evidence of a CWD susceptibility factor in the white-tailed deer population.