OMIA 002133-9615 : Skeletal dysplasia, FGF4-retrogene-related in Canis lupus familiaris

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Cross-species summary: A form of disproportionate dwarfism, characterized by short limbs

Mapping: Brown et al. (2017) reported that a "genome-wide association analysis in a cohort of Nova Scotia duck tolling retrievers (NSDTRs) with and without severe SD identified a significant association on CFA12 due to a 12-Mb associated haplotype, of which 1.9 Mb was found to be shared in chondrodystrophoid breeds."

Molecular basis: Brown et al. (2017): an FGF4 retrogene insertion in chromosome CFA12 (12: g.33710178_33710179insMF040221.1; CanFam3) is "responsible for SD [skeletal dysplasia] in NSDTR [Nova Scotia Duck Tolling retrievers] . . . the insertion on CFA12 is 3,209 bp long (GenBank accession no. MF040221) and includes parental FGF4 cDNA (i.e., FGF4 exons spliced without introns) . . . . The insert also contains a majority of the predicted 5′-untranslated region (UTR), which includes the transcription start site (TSS) as only PCR primers FGF4_TSS.F1 and FGF4.R1 yielded a product in RT-PCR using cDNA from neonatal beagle IVD . . . . The insertion location is intergenic between the 3′-UTR of OGFRL1 ∼9.5 kb on the proximal side and ∼350 kb to the RIMS1 gene on the distal side." Because the retrogene is not included in NCBI's Gene database, the table below lists the normal FGF4 gene.

Clinical features: Brown et al. (2017): "Relative to the unaffected dog, the mildly SD-affected NSDTR has cranial bowing of the radius. Radiographic changes in the more severely SD-affected NSDTR include moderate cranial bowing of the radius, physeal widening, and incongruity of the elbow joint with the shape of the semilunar notch of the ulna being elongated."

Breed: Nova Scotia Duck Tolling retriever.


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Nova Scotia Duck Tolling retriever Skeletal dysplasia, FGF4-retrogene-related FGF4 insertion, gross (>20) CanFam 3 12 g.33710178_33710179insMF040221 " the insertion on CFA12 is 3,209 bp long (GenBank accession no. MF040221) and includes parental FGF4 cDNA (i.e., FGF4 exons spliced without introns) . . . ." 2017 29073074


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2019 Tellegen, A.R., Dessing, A.J., Houben, K., Riemers, F.M., Creemers, L.B., Mastbergen, S.C., Meij, B.P., Miranda-Bedate, A., Tryfonidou, M.A. :
The dog as a model for osteoarthritis: the FGF4 retrogene insertion may matter. J Orthop Res :, 2019. Pubmed reference: 31373395. DOI: 10.1002/jor.24432.
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.
1975 Braund, K.G., Ghosh, P., Taylor, T.K.F., Larsen, L.H. :
Morphological studies of the canine intervertebral disc: the assignment of the Beagle to the achondroplastic classification Research in Veterinary Science 19:167-172, 1975. Pubmed reference: 1166121.

Edit History

  • Created by Frank Nicholas on 25 Oct 2017
  • Changed by Frank Nicholas on 25 Oct 2017
  • Changed by Frank Nicholas on 26 Oct 2017
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  • Changed by Frank Nicholas on 12 Jun 2020