FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11476-11481
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number43
DOIs
StatePublished - Oct 24 2017

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Extremities
Dogs
Dog Diseases
Intervertebral Disc Degeneration
Bone and Bones
Genome-Wide Association Study
Odds Ratio
Genome
Genes
Intervertebral disc disease

Keywords

  • Chondrodysplasia
  • Dysplasia
  • Genetic
  • GWAS
  • Inherited

ASJC Scopus subject areas

  • General

Cite this

FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. / Brown, Emily A.; Dickinson, Peter J; Mansour, Tamer; Sturges, Beverly; Aguilar, Miriam; Young, Amy E.; Korff, Courtney; Lind, Jenna; Ettinger, Cassandra L.; Varon, Samuel; Pollard, Rachel E; Brown, Charles; Raudsepp, Terje; Bannasch, Danika L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 43, 24.10.2017, p. 11476-11481.

Research output: Contribution to journalArticle

Brown, Emily A. ; Dickinson, Peter J ; Mansour, Tamer ; Sturges, Beverly ; Aguilar, Miriam ; Young, Amy E. ; Korff, Courtney ; Lind, Jenna ; Ettinger, Cassandra L. ; Varon, Samuel ; Pollard, Rachel E ; Brown, Charles ; Raudsepp, Terje ; Bannasch, Danika L. / FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 43. pp. 11476-11481.
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