FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Academic Article uri icon


  • Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology.

published proceedings

  • Proc Natl Acad Sci U S A

altmetric score

  • 73.45

author list (cited authors)

  • Brown, E. A., Dickinson, P. J., Mansour, T., Sturges, B. K., Aguilar, M., Young, A. E., ... Bannasch, D. L.

citation count

  • 59

complete list of authors

  • Brown, Emily A||Dickinson, Peter J||Mansour, Tamer||Sturges, Beverly K||Aguilar, Miriam||Young, Amy E||Korff, Courtney||Lind, Jenna||Ettinger, Cassandra L||Varon, Samuel||Pollard, Rachel||Brown, C Titus||Raudsepp, Terje||Bannasch, Danika L

publication date

  • October 2017