Abstract
Premature degeneration of the intervertebral disc and its association with specific chondrodystrophic dog breeds has been recognized for over a century. Several lines of evidence including disease breed predisposition, studies suggesting heritability of premature intervertebral disc degeneration (IVDD) and association of a dog chromosome 12 (CFA 12) locus with intervertebral disc calcification have strongly supported a genetic component in IVDD in dogs. Recent studies documenting association of IVDD with an overexpressing FGF4 retrogene on CFA 12 have opened up new areas of investigation to further define the pathophysiology of premature IVDD. While preliminary data from studies investigating FGF4 retrogenes in IVDD implicate FGF4 overexpression as a major disease factor, they have also highlighted knowledge gaps in our understanding of intervertebral disc herniation which is a complex and multifactorial disease process.
Highlights
The list of inherited neurological disorders in companion and production animals is ever expanding
The CFA12 FGF4 retrogene has an extremely high allele frequency (>90%) in the general population of breeds such as Beagles, Dachshunds, French Bulldogs, and most spaniel breeds, and not surprisingly, this frequency increases when looking at the population of dogs that present with clinical intervertebral disc disease (IVDD) [42]
The presence of the CFA12 FGF4 retrogene was associated with a variable risk of presenting for surgery for IVDD from 5.5to 15.1-fold in different segregating and mixed breeds [42] and even within a relatively non-segregating breed such as the Dachshund, differences in disease prevalence have been noted between different breed types [47, 50]
Summary
Current Understanding of the Genetics of Intervertebral Disc Degeneration. Premature degeneration of the intervertebral disc and its association with specific chondrodystrophic dog breeds has been recognized for over a century. Several lines of evidence including disease breed predisposition, studies suggesting heritability of premature intervertebral disc degeneration (IVDD) and association of a dog chromosome 12 (CFA 12) locus with intervertebral disc calcification have strongly supported a genetic component in IVDD in dogs. Recent studies documenting association of IVDD with an overexpressing FGF4 retrogene on CFA 12 have opened up new areas of investigation to further define the pathophysiology of premature IVDD. While preliminary data from studies investigating FGF4 retrogenes in IVDD implicate FGF4 overexpression as a major disease factor, they have highlighted knowledge gaps in our understanding of intervertebral disc herniation which is a complex and multifactorial disease process
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