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Abstract Chronic wasting disease (CWD) is a highly transmissible spongiform encephalopathy impacting cervids. Variations in the prion protein gene ( PRNP ), encoding the prion protein (PrP), influence disease progression and susceptibility. Protein sequence is a key determinant of PrP strains and their capacity for interspecies transmission. Sequencing PRNP in white-tailed deer has revealed non-synonymous polymorphisms impacting disease—c.285A > C (Q95H) and c.286G > A (G96S). Previous PRNP amplification protocols misclassified homozygous and heterozygous deer due to allelic dropout by a widely used forward primer. We resequenced 586 deer previously classified as homozygous using a redesigned primer (designated Ov- PRNP -F2) and found 128 heterozygotes. Subsequently, we sequenced additional CWD-positive and CWD-negative deer using Ov- PRNP -F2 to correct for dropout and then estimated PrP variant susceptibility and CWD risk using 778 CWD-positive and 3,070 CWD-negative deer from 22 Illinois counties, the largest PRNP sequence dataset to date. Animals encoding PrP variant combination C (96S) and F (95H) were the least susceptible to CWD (OR = 0.03, p < 0.001) compared to deer encoding two copies of PrP variant A 95Q;96G. A novel finding is that deer encoding a single copy of PrP 95H were less susceptible to CWD compared to those with a single copy of PrP 96S (OR = 0.40, p < 0.001). The results support using genotyping methods to map susceptibility to CWD across the landscape, focusing on PrP variant frequencies to improve CWD epidemiological risk models.
London et al. (Tue,) studied this question.