Inherited Mutation Discovery

Discovery of a genetic mutation that causes chondrodystrophy (CDDY).

Did you know that some of the most popular short-legged, long-backed dog breeds may suffer from a genetic mutation and also at risk for paralysis caused by intervertebral disc disease (IVDD)?

In an ancient occurrence the marriage of the short-legged phenotype and a predisposition to IVDD came from when dogs became domesticated from wolves, a variation in size and shape of purebred dog breeds transpired from the breeding selection. One of the most extreme examples of breed differences was in limb length, with extremely short limbs defining many breeds.

The chondrodystrophy associated mutation occurred a long time ago. There are descriptions of short-legged dogs dating over 4,000 years ago and before this, short-legged dogs were depicted in carvings in ancient Egypt.

IVDD is an inherited disorder caused by chrondrodystrophy (CDDY), a condition of shorter legs and abnormal intervertebral discs in which the discs degenerate prematurely. As the discs press on the nerves of the spinal cord, a dog may experience pain, nerve damage, loss of bladder/bowel control and/or paralysis.

The mutation that causes dogs' short legs and susceptibility to IVDD is a functional fibroblast growth factor (FGF4) retrogene insertion on canine chromosome 12. A retrogene results from the retrotransposition of processed mRNA (messenger RNA). In this case, the mRNA is copied back into DNA and inserted into the chromosome. It is called "retro" because it is going backward to make a DNA copy from RNA.

Dog Breeds Identified with the FHF4 Genotype:

This mutation affects breeds from all over the world.

• Dachshund
  
• Beagle
  
• American Cocker Spaniel
• Coton de Tulear
  
• Miniature Poodle
  
• French Bulldog
  
• Maltese
  
• Pekingese
  
• Pembroke Welsh Corgi
  
• Basset Hound 
  
• Bichon Frise
  
• Cardigan Welsh Corgi
  
• Cavalier King Charles Spaniel
  
• Chesapeake Bay Retriever
  
• Chihuahua
  
• ​Dandie Dinmont Terrier
  
• English Springer Spaniel
  
• Nova Scotia Duck Tolling Retriever
  
• Toy Poodle
  
• Portuguese Water Dog
  
• Shih Tzu
  

More research is needed to better understand the impact of the discovery on a breed-specific level.

The following information was taken from an article insertion from a research team at the National Institutes of Health studying breed sizes and morphology that made this finding in 2009.