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Phenotype: Chondrodystrophy (CDDY) includes a short-legged phenotype as well as abnormal premature degeneration of intervertebral discs (also referred to as intervertebral disc disease, IVDD). These degenerated discs are susceptible to herniation. Multiple factors are thought to influence whether a particular disc herniates in an individual dog.
Mode of Inheritance: Autosomal dominant for intervertebral disc disease; semi-dominant for height
Alleles: N = Normal, CDDY = Chondrodystrophy
Breeds appropriate for testing: Nova Scotia Duck Tolling Retriever
Explanation of Results:
- Dogs with N/N genotype do not have the mutation for chondrodystrophy and therefore are not predicted to be at increased risk for intervertebral disc disease. They cannot transmit this chondrodystrophy variant to their offspring.
- Dogs with N/CDDY genotype will have leg shortening compared to N/N dogs and intervertebral disc disease, and are at risk for intervertebral disc herniation. They will transmit this CDDY variant to 50% of their offspring. Matings with N/N genotype dogs are predicted to produce 50% shorter-legged puppies at risk for intervertebral disc herniation.
- Dogs with CDDY/CDDY genotype will have leg shortening compared to N/N dogs and intervertebral disc disease, and are at risk for intervertebral disc herniation. If a CDDY/CDDY dog is bred, all of the puppies in the litter will have shorter legs and are also be at risk for intervertebral disc herniation, regardless of the mate's genotype.
Results of this test can be submitted to the OFA (Orthopedic Foundation for Animals)
Shorter legs in dogs are explained by two retrogene insertions of functional fibroblast growth factor 4 (FGF4). FGF4 gene is involved in many biological processes including bone development.
The first insertion discovered (Parker et al. 2009) is an FGF4-retrogene insertion in dog chromosome 18 (FGF4-18). This FGF4-18 insertion explains a short-legged phenotype known as chondrodysplasia (CDPA) in breeds such as Basset Hound, Pembroke Welsh Corgi, Dachshunds, West Highland White Terriers and Scottish Terriers. CDPA inheritance is considered to follow an autosomal dominant mode.
The Chondrodystrophy (CDDY) mutation was discovered by researchers in the Bannasch Laboratory at the University of California, Davis (Brown et al. 2017) as a second FGF4-retrogene insertion in dog chromosome 12. CDDY includes a short-legged phenotype and abnormal premature degeneration of intervertebral discs leading to susceptibility to Hansen’s type I intervertebral disc disease (IVDD). The intervertebral disc, which sits between vertebrae, is composed of an outer fibrous basket (annulus fibrosus) made of 70% collagen and an inner gel-like layer called the nucleus pulposus. These structures allow for flexibility of the vertebral column. In Chondrodystrophic breeds, premature calcification of the nucleus pulposus at early age (from birth to 1 year of age) results in degeneration of all discs in young dogs. These abnormal discs are predisposed to herniation into the spinal canal where the inflammation, and hemorrhage can cause severe pain and neurological dysfunction (myelopathy) termed Intervertebral Disc Disease or IVDD. IVDD has high mortality rate and high cost of surgical and medical veterinary care.
CDDY is inherited as a semi-dominant trait for height, meaning that dogs with 2 copies of the mutation are smaller than dogs with only 1 copy. With respect to IVDD, the inheritance follows a dominant mode, meaning that 1 copy of the FGF4-12 mutation is sufficient to cause disc degeneration and predispose dogs to disc herniation. Dogs that have both FGF4-12 and FGF4-18 show a more drastic reduction of leg length.
Testing for the CDDY variant in Nova Scotia Duck Tolling Retrievers can help breeders determine if CDDY is present among breeding stock and to identify dogs at risk for IVDD. Our tests assay for the causal variants, not for linked markers, therefore the genotypes are accurate and not inferred. Breeders can benefit from the test result to implement breeding strategies to reduce incidence of CDDY.
Type of Test
No copies of CDDY mutation.
1 copy of CDDY mutation. Dog has IVDD and is at risk for disc herniation. Mutation causes leg shortening compared to N/N dogs. When bred to an N/N dog, will produce 50% of normal sized puppies and 50% of puppies with shorter legs that also have IVDD and are at risk for disc herniation.
2 copies of CDDY. Dog has IVDD and is at risk for disc herniation. Mutation causes leg shortening compared to N/N dogs. Will produce 100% of puppies with shorter legs and IVDD who are at risk for disc herniation.
Brown, E.A., Dickinson, P.J., Mansour, T., Sturges, B.K., Aguilar, M., Young, A.E., Korff, C., Lind, J., Ettinger, C.L., Varon, S., Pollard, R., Brown, C.T., Raudsepp, T., & Bannasch, D.L. (2017). FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proceedings of the National Academy of Sciences of the United States of America, 114(43), 11476-11481. doi: 10.1073/pnas.1709082114
Batcher, K., Dickinson, P., Giuffrida, M., Sturges, B., Vernau, K., Knipe, M., Rasouliha, S.H., Drögemüller, C., Leeb, T., Maciejczyk, K., Jenkins, C.A., Mellersh, C., & Bannasch, D. (2019). Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs. Genes, 10 435. doi: 10.3390/genes.10060435
Murphy, B.G., Dickinson, P., Marcellin-Little, D.J., Batcher, K., Raverty, S., & Bannasch, D. (2019). Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype. Veterinary Pathology, 030098581986873. doi: 10.1177/0300985819868731