Breeding schemes for intervertebral disc disease in dachshunds: Is disc calcification score preferable to genotyping of the FGF4 retrogene insertion on CFA12?

Abstract

Background Approximately every fifth Dachshund is affected by disc herniation - a painful, hereditary condition which is typically preceded by disc calcification. Therefore, the selection of dogs suitable for breeding can be based on radiographic examination of calcification status. Recently, an insertion of an FGF4 retrogene on CFA12 has been identified and associated with the risk of developing disc herniation in chondrodystrophic breeds and a DNA test is now offered. In this study we investigate the incidence of disc herniation in the smooth-haired, long-haired and wire- haired Dachshund populations. We also evaluate and compare the accuracy of the two breeding schemes predicting the risk of disc herniation: the DNA test and the radiography based scheme. Results The overall incidence of disc herniation in Danish Dachshunds was 18% and no significant difference was found between the long-haired (17%), smooth-haired (22%) and wire-haired (16%) populations (p > 0.05). We found a significant association (p < 0.0001) between calcification status and the risk of disc herniation with a relative risk of 14.78. Using calcification status (≥ 5 or < 5 calcifications) as a risk indicator has a sensitivity of 0.79 and a specificity of 0.91. A significant association between the FGF4 retrogene insertion and the disc calcification status was found in the wire-haired population (p < 0.0001) where the DNA test has a sensitivity of 1.0 and a specificity of 0.14. In the long- and smooth-haired populations no association was found (p > 0.05) and here the insertion allele was almost fixed. Conclusion Our results show that the FGF4 retrogene insertion on CFA12 is not a valid risk indicator on its own. Relying on the DNA test will have an irreversible effect on the Dachshund breed excluding almost all dogs from breeding. Thus, using calcification status remains the most reliable breeding scheme for disc herniation in Dachshunds.

FGF4L2 retrogene copy number is associated with intervertebral disc calcification and vertebral geometry in Nova Scotia Duck Tolling Retrievers

“…The additive effect of the FGF4L2 retrogene on IVD calcification has now been demonstrated in several studies where interrogation of data from segregating populations has made analysis possible. 1,18 In addition to the current study, similar effects were shown across breeds presenting for surgically confirmed disc extrusions 1 and in Wire-haired Danish Dachshunds where genotype and calcification Table 1-Median (range) and coefficient of variation of geometric parameters of the third cervical vertebra in 21 dogs with 0 (n = 7), 1 (8), or 2 FGF4L2 retrogenes (7). screening scores were reported.…”

“…It has been shown that the FGF4L2 retrogene is sufficient to cause chondrodystrophy and associated premature IVD degeneration; 5 however, only circumstantial evidence suggests that FGF4L2 retrogene dosage is associated with clinical disease severity. IVD calcification scores have been shown to be related to risk for "clinical" IVDD, [18][19][20][21][22] and the number of calcified IVD, as in the current study, is associated with genotype. 1,18 The effect of the FGF4L2 retrogene on IVD calcification appears to be definable in segregating populations; however, considerable variation in calcification is present even within the FGF4L2 homozygous populations of fixed and segregating breeds alike.…”

“…screening scores were reported. 18 The number of calcified IVD has been shown to be associated with the risk of overt clinical disease in Dachshunds and Pekingese dogs, [19][20][21][22] and radiographic screening has been used in an attempt to reduce disease incidence through selective breeding, specifically within the Dachshund breed. The impact of this approach on subsequent calcification scores and clinical disease has however been limited, 23 potentially due to a combination of factors including suboptimal enrollment and compliance within the breeding population and methodological limitations.…”

“…Retrospective analysis using either approach will always identify animals that did not develop overt clinical disease and that would have been deemed less desirable for breeding. In 1 study, 18 genotypically selecting for wildtype long-haired dogs would have precluded 92% of dogs or 58% of dogs if heterozygous dogs were included; however, calcification breeding scores (estimated breeding values) would have also precluded 48% of dogs that did not develop overt clinical disease. It has been shown that the FGF4L2 retrogene is sufficient to cause chondrodystrophy and associated premature IVD degeneration; 5 however, only circumstantial evidence suggests that FGF4L2 retrogene dosage is associated with clinical disease severity.…”

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part Two of Two

“…The increased application of genome and exome sequencing has facilitated a new era of understanding painful and progressive pathologies [3]. The genetic component to polygenic pathologies such as IVDD has been increasingly more characterized, with genome-wide association studies finding mutants, variants, and polymorphisms to genes that adversely influence the structure and function of the intervertebral disc (IVD) [4]. These genes may either gain or lose their function in supporting the IVD, leading to degenerative, apoptotic, and inflammatory signaling pathways that stimulate the pathogenesis of IVD degeneration [5].…”