Chondrodystrophy (CDDY and IVDD)
Breed: Rabbit Dachshund/ Wirehaired
Generic Phene Data
Breeds
Relevance Rating: There is some evidence or research available for these breeds
Relevance Rating: The test is unknown, there is no evidence (i.e. research) available, or it has not been evaluated yet. These tests may or may not be meaningful for these breeds
General
Disease Name
Chondrodystrophy (CDDY and IVDD)
OMIA
189
Gene Name
FGF4 retrogene insertion on Ch 12:33,710,200 Mb (canFam3)
Mutation
On Ch 12; FGF4 retrogene insertion at 33,710,200 Mb
Test Type
Genetic Disease/Disorder
Details
Chondrodystrophy Type 1 IVDD (CDDY) indicates a short-legged phenotype, as well as abnormal and premature degeneration of interverebral discs leading to increased risk of intervertebral disc herniation. This means that the dog will have short legs and a stiffened spine - the spine of which may go on to degenerate, even in young dogs, causing inflammation, hemorrage, severe pain, and neurological problems. Inheritance is autosomal dominant for intervertebral disc disease, but semi-dominant for height. There are a number of breeds currently undergoing research related to this condition, and a comprehensive study in 2019 investigated breed distribution of the mutation. Understanding the allele frequencies is key to recommendations in testing and how to use test results. "For those breeds in which CDDY has been documented to segregate, in other words, both the CDDY allele and the normal allele are present in the breed, genetic testing is recommended. The results of this test can assist in breeding decisions and should be shared with the animal?s veterinarian to assist in clinical decisions. The CDDY allele has been found to be present in mixed breed dogs and therefore testing is recommended for these animals as well. For breeds where the CDDY allele is fixed in the population, in other words only the CDDY is present or allele frequency is 1.0, genetic testing for CDDY is not necessary, in these cases it is reasonable to assume that all dogs in that breed will be homozygous for CDDY (CDDY/CDDY)." [UC Davis/VGL, 2020] A current list of mutation frequency can be found from VHL:
https://vgl.ucdavis.edu/test/cddy-cdpa
. Other GTPs may also be able to provide frequency of muation information.
Details 2
"Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs... Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species... Extensive examination of growth plates has been performed on many of these short-legged dog breeds (dachshund, Pekingese, French bulldog, spaniels, beagle), as these breeds are also prone to intervertebral disc disease (IVDD). Histopathological analysis of the bones of puppies from these breeds demonstrated that their short stature is due to defects in endochondral ossification, the process whereby cartilage is replaced with bone, in the developing limb. The long bone growth plates show disorganization of the proliferative zone and reduction in the depth of the maturation zone. In addition to the long bones, similar but more subtle changes exist in endochondral ossification of the vertebral bodies...In chondrodystrophic dogs, the nucleus pulposus is gradually replaced by chondrocyte-like cells in chondroid metaplasia (or metamorphosis) that occurs between birth and 1 y of age. Recent studies have shown that in advanced stages of degeneration in nonchondrodystrophoid dogs there is also replacement of notochordal cells by chondrocyte-like cells, similar to the changes observed in chondrodystrophoid dogs, although this happens at an older age. Hansen described the two different types of canine IVD prolapse as type I and type II. Type I occurs exclusively in chondrodystrophic breeds and is characterized by premature degeneration of all discs in young dogs. In type I disc disease, the calcified nucleus pulposus may undergo an explosive herniation through the annulus fibrous into the vertebral canal, resulting in inflammation and hemorrhage and causing severe pain and neurological dysfunction..." [Brown et. al, 2017]
Application Information
The application of this test will vary by breed. There is research (Batcher et. al) that indicates some populations of breeds, such as dachshund varieties, are "fixed" for this mutation. This means, in practice, that there are very few dogs in the population who do not carry the mutation, and therefore it may not be possible to breed away from - e.g. all dogs who are tested are "affected." It is strongly recommended that you review the breed-specfic references provided here and/or contact your local breed club for support in breeding decisions. Many breed clubs strongly recommend you undertake a clinical examination before breeding. This is extremely valuable in identifying lower-risk dogs. If you are testing for information on your own dog, and not for breeding plans, it is important to remember that a dog who tests affected for this mutation is at risk for developing the condition, but the test is not an indication of severity, age of onset, or that the disease will manifest in the dog's lifetime. There is research indicating that there could be other factors (such as environmental factors) that impact disease development. Your breed club, breed advisor, veterinarian, or test provider should be able to provide more information.
Published
2017, 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. : FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proc Natl Acad Sci U S A 114:11476-11481, 2017. Pubmed reference: 29073074. DOI: 10.1073/pnas.1709082114.
Published 2
Batcher, K., P. Dickinson, M. Giuffrida, B. Sturges, K. Vernau, M. Knipe, S. H. Rasouliha, C. Drogemuller, T. Leeb, K. Maciejczyk, C. A. Jenkins, C. Mellersh and D. Bannasch, (2019) Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs. Genes (Basel), 10,
Body/System/Process
Skeletal
Inheritance
ADIP
Breed Specific Info
Researched Breeds
Alpine Dachsbracke, American Cocker Spaniel, Australian Shepherd, Basset Hound, Bavarian Mountain Hound, Beagle, Bichon Frise, Boykin Spaniel, Cardigan Welsh Corgi, Cavalier King Charles Spaniel, Chesapeake Bay Retriever, Chihuahua, Chinese Crested, Clumber Spaniel, Coton de Tulear, Dachshund, Dandie Dinmont Terrier, Danish Swedish Farmdog, English Springer Spaniel, Entlebucher Mountain Dog, French Bulldog, German Hound, Havanese, Jack Russell Terrier, Maltese, Nova Scotia Duck Tolling Retriever, Pekingese, Pembroke Welsh Corgi, Pinscher (Miniature), Poodle (Miniature and Toy), Poodle (Standard), Portuguese Water Dog, Pug, Rat Terrier, Russian Tsvetnaya Bolonka, Schweizer Laufhund, Schweizerischer Niederlaufhund, Scottish Terrier, Sealyham Terrier, Shih Tzu, Skye Terrier, and Yorkshire Terrier
Breed-specific 1
ALL BREEDS TESTING FOR THIS MUTATION
Breed-specific 1 Details
Breed-specific 2
Dachschund (all varieties)
Breed-specific 2 Details
There is research indicating that most (possibly all) dachshunds are "fixed" for this mutation. The Breed Council for dachshunds in the UK have recommended clinical (x-ray) screening for identifying clinical risks, and to aid in breeding decisions for this disease. You can find further information in the Get a GRIHP article:
https://dogwellnet.com/content/health-and-breeding/breeds/breed-specific-health-reports/get-a-grihp-on-dachshunds-r696/
GTP Test-Specific Data
Genomia s.r.o
GTP
GTP Name
Genomia s.r.o
GTP Disease Name
CDDY Chrondrodystrophy, IVVD risk & CDPA
Gene Name
FGF4
Mutation
Chromasome 12
Mutation Comment
insertion on CFA12 is 3,209 bp long
Nature of test
mutation test
EVG Diagnostics
GTP
GTP Name
EVG Molecular Diagnostics
Gene Name
FGF4
Mutation
Chromasome 12