Phenotypic effects of FGF4 retrogenes on intervertebral disc disease in dogs

Kevin Batcher, Peter J Dickinson, Michelle Giuffrida, Beverly Sturges, Karen Vernau, Marguerite Knipe, Sheida Hadji Rasouliha, Cord Drögemüller, Tosso Leeb, Kimberly Maciejczyk, Christopher A. Jenkins, Cathryn Mellersh, Danika L Bannasch

Research output: Contribution to journalArticle

Abstract

Two FGF4 retrogenes on chromosomes 12 (12-FGF4RG) and 18 (18-FGF4RG) contribute to short-limbed phenotypes in dogs. 12-FGF4RG has also been associated with intervertebral disc disease (IVDD). Both of these retrogenes were found to be widespread among dog breeds with allele frequencies ranging from 0.02 to 1; however, their additive contribution to disease is unknown. Surgical cases of IVDD (n = 569) were evaluated for age of onset, disc calcification, and genotypes for the FGF4 retrogenes. Multivariable linear regression analysis identified the presence of one or two copies of 12-FGF4RG associated with significantly younger age at first surgery in a dominant manner. 18-FGF4RG had only a minor effect in dogs with one copy. Multivariable logistic regression showed that 12-FGF4RG had an additive effect on radiographic disc calcification, while 18-FGF4RG had no effect. Multivariable logistic regression using mixed breed cases and controls identified only 12-FGF4RG as highly associated with disc herniation in a dominant manner (Odds Ratio, OR, 18.42, 95% Confidence Interval (CI) 7.44 to 50.26; P < 0.001). The relative risk for disc surgery associated with 12-FGF4RG varied from 5.5 to 15.1 within segregating breeds and mixed breeds. The FGF4 retrogene on CFA12 acts in a dominant manner to decrease the age of onset and increase the overall risk of disc disease in dogs. Other modifiers of risk may be present within certain breeds, including the FGF4 retrogene on CFA18.

Original languageEnglish (US)
Article number435
JournalGenes
Volume10
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Dogs
Age of Onset
Logistic Models
Dog Diseases
Chromosomes, Human, Pair 12
Gene Frequency
Linear Models
Odds Ratio
Genotype
Regression Analysis
Confidence Intervals
Phenotype
Intervertebral disc disease

Keywords

  • Breed
  • Canis lupus familiaris
  • Inherited
  • Intervertebral disc disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Phenotypic effects of FGF4 retrogenes on intervertebral disc disease in dogs. / Batcher, Kevin; Dickinson, Peter J; Giuffrida, Michelle; Sturges, Beverly; Vernau, Karen; Knipe, Marguerite; Rasouliha, Sheida Hadji; Drögemüller, Cord; Leeb, Tosso; Maciejczyk, Kimberly; Jenkins, Christopher A.; Mellersh, Cathryn; Bannasch, Danika L.

In: Genes, Vol. 10, No. 6, 435, 01.06.2019.

Research output: Contribution to journalArticle

Batcher, K, Dickinson, PJ, Giuffrida, M, Sturges, B, Vernau, K, Knipe, M, Rasouliha, SH, Drögemüller, C, Leeb, T, Maciejczyk, K, Jenkins, CA, Mellersh, C & Bannasch, DL 2019, 'Phenotypic effects of FGF4 retrogenes on intervertebral disc disease in dogs', Genes, vol. 10, no. 6, 435. https://doi.org/10.3390/genes10060435
Batcher, Kevin ; Dickinson, Peter J ; Giuffrida, Michelle ; Sturges, Beverly ; Vernau, Karen ; Knipe, Marguerite ; Rasouliha, Sheida Hadji ; Drögemüller, Cord ; Leeb, Tosso ; Maciejczyk, Kimberly ; Jenkins, Christopher A. ; Mellersh, Cathryn ; Bannasch, Danika L. / Phenotypic effects of FGF4 retrogenes on intervertebral disc disease in dogs. In: Genes. 2019 ; Vol. 10, No. 6.
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abstract = "Two FGF4 retrogenes on chromosomes 12 (12-FGF4RG) and 18 (18-FGF4RG) contribute to short-limbed phenotypes in dogs. 12-FGF4RG has also been associated with intervertebral disc disease (IVDD). Both of these retrogenes were found to be widespread among dog breeds with allele frequencies ranging from 0.02 to 1; however, their additive contribution to disease is unknown. Surgical cases of IVDD (n = 569) were evaluated for age of onset, disc calcification, and genotypes for the FGF4 retrogenes. Multivariable linear regression analysis identified the presence of one or two copies of 12-FGF4RG associated with significantly younger age at first surgery in a dominant manner. 18-FGF4RG had only a minor effect in dogs with one copy. Multivariable logistic regression showed that 12-FGF4RG had an additive effect on radiographic disc calcification, while 18-FGF4RG had no effect. Multivariable logistic regression using mixed breed cases and controls identified only 12-FGF4RG as highly associated with disc herniation in a dominant manner (Odds Ratio, OR, 18.42, 95{\%} Confidence Interval (CI) 7.44 to 50.26; P < 0.001). The relative risk for disc surgery associated with 12-FGF4RG varied from 5.5 to 15.1 within segregating breeds and mixed breeds. The FGF4 retrogene on CFA12 acts in a dominant manner to decrease the age of onset and increase the overall risk of disc disease in dogs. Other modifiers of risk may be present within certain breeds, including the FGF4 retrogene on CFA18.",
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