Accurate Genomic Predictions for Chronic Wasting Disease in North American Elk

The geographic expansion of chronic wasting disease (CWD) in North American elk (Cervus canadensis) has not been well-mitigated by traditional best management practices, diagnostic surveillance, and depopulation of positive herds. Using a custom Affymetrix Axiom® genetic variant array, we demonstrate that differential susceptibility to CWD is highly heritable (h2 = 0.630 ± 0.061 - 0.678 ± 0.056) among farmed North American elk; with loci other than PRNP involved. Genome-wide association analyses using 173,674 quality filtered variants for a geographically diverse cohort of 904 farmed North American elk (n = 357 CWD positive; n = 547 CWD non-detect) confirmed the prion gene (PRNP codon 132 Met→Leu and promoter variants) as a large-effect risk locus (P-value < 5.135E-08), as evidenced by the estimated proportion of phenotypic variance explained (PVE ≥ 0.032). However, more phenotypic variance was collectively explained by loci other than PRNP. Genomic best linear unbiased prediction (GBLUP; n = 173,674 markers) with k-fold cross validation (k = 3; k = 5) and random sampling (n = 50 iterations) for the same cohort of 904 farmed North American elk produced mean genomic prediction accuracies ≥ 0.791; thereby providing a foundation to explore a genomically-estimated CWD genetic improvement program.