In the late 1960s, wildlife facilities in Colorado first saw signs of chronic wasting disease (CWD) in North American elk. This disease, which is characterized by weight loss, behavioral changes, and movement problems, wasn’t identified as a prion disease until the late 1970s. In the coming decades, the disease has spread to dozens of states in the U.S., half the provinces in Canada, and has also made its way into Europe and Asia. Traditional methods of curbing this disease, including containment and depopulation of CWD-positive herds, seem to have limited success; therefore, researchers are turning to other methods to manage the disease.

Recent research led by Christopher Seabury’s team at Texas A&M University took a genome-based approach to predict CWD susceptibility in North American elk. 

The team, which recently published this work in G3: Genes|Genomes|Genetics,created a custom genetic variant array containing 173,674 variants to analyze a geographically diverse cohort of farmed North American elk. Some elk had CWD while others did not. Based on these data, the researchers could identify variants associated with CWD and estimate an individual’s CWD susceptibility by capturing both risk and protective alleles.

Overall, the researchers found that CWD is heritable, polygenic, and involves loci beyond   PRNP, which is a major risk locus for CWD. The widely accepted explanation of CWD as a prion disease is that a misfolded PrP protein (encoded by the PRNP gene) can infect other elk and cause further misfolding of that animal’s PrP protein. The susceptibility to misfolding depends on the infected animal’s PRNP gene, with certain PRNP variants more susceptible to misfolding than others. The researchers also found that 17 other variants beyond PRNP were involved in CWD. This includes genes involved in neuronal development, synaptic plasticity, olfactory receptors, and proteoglycan synthesis and reflect pathways involved in prior entry or spread and neuronal dysfunction. However, it should also be noted that the genome-wide polygenic effects are a key component driving differential susceptibility to CWD in North American elk.

To predict CWD susceptibility, the researchers use genomic best linear unbiased prediction models with k-fold cross validation and random sampling. Their initial model resulted in a mean genomic prediction accuracy of ≥ 0.791, mean specificities of ≥ 0.8595, mean sensitivities of ≤ 0.6807, and mean area under the curve of ≥ 0.8352. Since the publication of this work, the authors noted that they have improved the prediction accuracy and sensitivity of their model. The researchers have also built a similar model for farmed North American white-tailed deer.

Understanding how genetics impacts CWD susceptibility can help support breeding programs to reduce passing CWD to future generations of farmed North American elk. 

References

  • Seabury CM, Bhattarai EK, Brun M, et al. Accurate Genomic Predictions for Chronic Wasting Disease in North American Elk. G3 Genes|Genomes|Genetics. 2026;jkag082., https://doi.org/10.1093/g3journal/jkag082 

  • Seabury CM, Oldeschulte DL, Bhattarai EK, et al. Accurate Genomic Predictions for Chronic Wasting Disease in U.S. White-Tailed Deer. G3 Genes|Genomes|Genetics. 2020;10(4), https://doi.org/10.1534/g3.119.401002

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