Retrogenes in dogs – CDPA for short legs and CDDY for premature disc degeneration

Katariina Mäki, PhD

Two retrogenes are currently known to affect leg length in dogs: CDPA and CDDY. It is imperative to take both retrogenes into account when breeding dogs, as they may have a significant impact on dogs’ well-being.

Short legs are caused by chondrodysplasia (CDPA)

Short legs are caused by a hereditary disorder of bone growth and ossification. The disorder is characterized by dwarfism and abnormal body proportions, giving the short-legged dog breeds their characteristic appearance.

Parker et al. (2009) concluded that short-limbed expression defines at least 19 dog breeds, including Basset Hounds, Dachshunds and Corgis. They defined short-legged dogs as those meeting the following criteria:

• Withers height of less than 15 inches (38.1 cm) and a withers height to body length ratio of less than one.
• The skeletal structure of the limbs is heavy and large in relation to the size of the dog.
• Forelimbs bent, curved and/or paws turned outwards.

The growth plates of the bones close too early

Short-legged dogs have an extra copy of a growth factor gene called functional fibroblast growth factor 4 (FGF4) on chromosome 18, known as the CDPA.

The FGF4 growth factor gene acts as a promoter of tissue growth during individual development. The excess copy of the gene causes over-expression of the gene, which causes the growth process of long bones in the limbs to be timed at the wrong point in the foetal period. The growth plates of the limb bones close too early, preventing the bones from developing to their normal size, and the limbs become short and curved (Parker et al. 2009).

In addition to CDPA on chromosome 18, a study published in summer 2017 by Brown et al. showed that the same retrogene is also present on chromosome 12 in some dogs. This retrogene, CDDY, also causes shortening of the limbs.

When present together, CDPA and CDDY cause significantly shorter limbs than either retrogene alone.

CDDY is a risk gene for intervertebral disc disease (IVDD)

Of note in the summer 2017 study was the discovery of the role of the CDDY in intervertebral disc disease: it acts as a risk gene. The researchers deduced this from the fact that, for example, Cairn Terriers and West Highland White Terriers do not have the disease, despite the presence of CDPA. On the other hand, the disease is relatively high in breeds with only CDDY but no CDPA.

Short-legged dogs have been referred to as chondrodystrophic for decades, so the discovery of CDDY in 2017 has created a new classification that may cause confusion. Currently, the term chondrodystrophy refers to the early degeneration of the intervertebral discs due to CDDY.

To summarize:
Two retrogenes causing shortening of the limbs have been identified

1. Chondrodysplasia (CDPA) - A retrogene insertion on chromosome 18 shortens limbs dramatically. Dogs with two copies of CDPA have shorter limbs than dogs with only one copy. CDPA is therefore additive / incompletely dominant.

2. Chondrodystrophy (CDDY) - A retrogene insertion on chromosome 12 shortens limbs less than CDPA but causes premature degeneration of the intervertebral discs and is therefore a risk allele for intervertebral disc disease. The effect of CDDY on the risk of disc disease is dominant and on limb length additive / incompletely dominant. Thus, two copies of CDDY shorten limbs more than one copy.

CDPA and CDDY in dog breeds

Parker et al. (2009) reported that CDPA is fixed (frequency 100%) in the following 15 short-legged breeds: Basset Hound, Cairn Terrier, Dandie Dinmont Terrier, Pekingese, Lancashire Heeler, Swedish Vallhund, Dachshunds, Norwich Terrier, Petit Basset Griffon Vendéen, Shih Tzu, Skye Terrier, Tibetan Spaniel, and West Highland White Terrier, as well as Welsh Corgi Cardigan and Pembroke.

Batcher et al. (2019) found CDPA in 32 breeds and CDDY in 40 breeds. Both retrogenes were present in 23 breeds (Table 1). CDPA was fixed in 15 breeds, meaning that no or very few normal alleles exist in these breeds. CDDY was fixed in the Beagle, the Cavalier King Charles Spaniel and Clumber Spaniel, and near fixed in the Dachshund, Cocker Spaniel, American Cocker Spaniel and French Bulldog.

In a large study by Donner et al. (2023), the frequency of CDDY was 11.4% in mixed-breed dogs and 13.9% in pedigree dogs. CDDY was detected in 89 breeds or breed varieties with a frequency of more than 1%.

Table 1. CDDY and CDPA in the breeds studied by Batcher et al. 2019 (due to the large size of the table, only part of it is presented here; the full table is presented in Batcher et al. 2019 online publication).

*Frequency indicates how common the retrogene is in the population of studied dogs.

Risk of herniated discs, paralysis, osteoarthritis

In the majority of chondrodystrophic dogs, the intervertebral discs in the spine degenerate prematurely (Hansen 1952). Degenerated discs are prone to herniation into the spinal canal and even rupture (Table 2).

CDDY sets therefore a high susceptibility to disc herniation. It also lowers the age at morbidity: chondrodystrophic dogs were significantly smaller (median weight 8.1 vs. 25.0 kg) and younger than other dogs at the time of surgical treatment (5,5 vs. 9,0 years; Batcher ym. 2019).

Dogs with short legs are prone to varying degrees of angular front limb deformity (ALD), which refers to an excessively curved limb conformation, seen in some short-legged dog breeds. Common characteristics of ALD include carpal valgus, front limb rotation, elbow incongruity, and lateral radial head subluxation (Lappalainen et al. 2023). These may cause osteoarthritis, lameness, pain and discomfort in affected dogs.

Table 2. Welfare risks associated to CDPA and CDDY.

Lists of CDDY frequencies in different breeds

US Davis Veterinary Medicine

Wisdom Panel

References and more information

Interviews with expert veterinarians: Juha Kallio, Anu Lappalainen, Kirsti Schildt

Bannasch et al. 2022. The Effects of FGF4 Retrogenes on Canine Morphology. Genes (Basel). 13(2):325. doi: 10.3390/genes13020325.

Batcher et al. 2019. Phenotypic effects of FGF4 retrogenes on intervertebral disc disease in dogs. Genes 10:435. doi: 10.3390/genes10060435.

Brown et al. 2017. FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proc. Natl. Acad. Sci. USA. 114: 11476–11481. doi: 10.1073/pnas.1709082114.

Donner et al. 2023. Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLoS Genet 19(2): e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Hansen 1952. A pathologic-anatomical study on disc degeneration in dog, with special reference to the so-called enchondrosis intervertebralis. Acta Orthop. Scand. Suppl. 11: 1–117. doi: 10.3109/ort.1952.23.suppl-11.01.

Koskinen 2016. Kyynärnivelen inkongruenssin arvioiminen röntgenkuvista sekä esiintyvyys kondrodystrofisilla koiraroduilla (Assessment of elbow joint incongruity on radiographs and prevalence in chondrodystrophic dog breeds). Licentiate’s thesis in Veterinary Medicine, University of Helsinki.

Lappalainen: Kyynärnivelen inkongruenssi (Elbow incongruency), www.kennelliitto.fi.

Lappalainen: Selkänikamien välilevyjen rappeutuminen ja välilevykalkkeutumat (Degeneration and calcification of the intervertebral discs). www.kennelliitto.fi.

Lappalainen et al. 2023. Breed-typical front limb angular deformity is associated with clinical findings in three chondrodysplastic dog breeds. Front. Vet. Sci. 9. DOI:10.3389/fvets.2022.1099903.

Parker et al. 2009. An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325: 995–998. doi: 10.1126/science.1173275.