How certain dog genes affect age and severity of disc disease

Abstract

Tworetrogenes on chromosomes 12 (12-RG) and 18 (18-RG) contribute to short-limbed phenotypes in dogs. 12-RG has also been associated with intervertebral disc disease (IVDD). Both of these retrogenes were found to be widespread among dog breeds with allele frequencies ranging from 0.02 to 1; however, their additive contribution to disease is unknown. Surgical cases of IVDD (= 569) were evaluated for age of onset, disc calcification, and genotypes for theretrogenes. Multivariable linear regression analysis identified the presence of one or two copies of 12-RG associated with significantly younger age at first surgery in a dominant manner. 18-RG had only a minor effect in dogs with one copy. Multivariable logistic regression showed that 12-RG had an additive effect on radiographic disc calcification, while 18-RG had no effect. Multivariable logistic regression using mixed breed cases and controls identified only 12-RG as highly associated with disc herniation in a dominant manner (Odds Ratio, OR, 18.42, 95% Confidence Interval (CI) 7.44 to 50.26;< 0.001). The relative risk for disc surgery associated with 12-RG varied from 5.5 to 15.1 within segregating breeds and mixed breeds. Theretrogene on CFA12 acts in a dominant manner to decrease the age of onset and increase the overall risk of disc disease in dogs. Other modifiers of risk may be present within certain breeds, including theretrogene on CFA18.