Genome-Wide Association Analysis for Chronic Superficial Keratitis in the Australian Racing Greyhound

Abstract

Chronic superficial keratitis (CSK) is a progressive inflammatory condition of the eye (cornea) that can cause discomfort and blindness. Differential disease risk across dog breeds strongly suggests that CSK has a genetic basis. In addition to genetic risk, the occurrence of CSK is exacerbated by exposure to ultraviolet light. Genome-wide association analysis considered 109 greyhounds, 70 with CSK and the remainder with normal phenotype at an age over four years. Three co-located variants on CFA18 near the 5′ region of the Epidermal Growth Factor Receptor (EGFR) gene were associated with genome-wide significance after multiple-test correction (BICF2P579527, CFA18: 6,068,508, praw = 1.77 × 10−7, pgenome = 0.017; BICF2P1310662, CFA18: 6,077,388, praw = 4.09 × 10−7, pgenome = 0.040; BICF2P160719, CFA18: 6,087,347, praw = 4.09 × 10−7, pgenome = 0.040) (canFam4)). Of the top 10 associated markers, eight were co-located with the significantly associated markers on CFA18. The associated haplotype on CFA18 is protective for the CSK condition. EGFR is known to play a role in corneal healing, where it initiates differentiation and proliferation of epithelial cells that in turn signal the involvement of stromal keratocytes to commence apoptosis. Further validation of the putative functional variants is required prior to their use in genetic testing for breeding programs.

143550

“…Although the tendency that the lesions occur more likely in older dogs and the dogs with lesions have worse sport results can be suspected, in our study these differences were not significant. This lack of differences seems to be related to the fact that the sport carrier of the dogs is limited, so none of the dogs examined in this study was older than 7.5 years and that is why the group was more homogenous regarding the age than groups examined in other ophthalmological studies (Guandalini et al 2017, Balicki et al 2021, Palmer et al 2021, Crasta et al 2022, Karamatic et al 2022. Although median ranking points were lower in the dogs with ocular lesions, the difference was not significant since many other factors (fitness and physical performance) are important for the result.…”

143549

“…Although the tendency that the lesions occur more likely in older dogs and the dogs with lesions have worse sport results can be suspected, in our study these differences were not significant. This lack of differences seems to be related to the fact that the sport carrier of the dogs is limited, so none of the dogs examined in this study was older than 7.5 years and that is why the group was more homogenous regarding the age than groups examined in other ophthalmological studies (Guandalini et al 2017, Balicki et al 2021, Palmer et al 2021, Crasta et al 2022, Karamatic et al 2022. Although median ranking points were lower in the dogs with ocular lesions, the difference was not significant since many other factors (fitness and physical performance) are important for the result.…”