Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs.

Batcher, Kevin; Dickinson, Peter; Giuffrida, Michelle; Sturges, Beverly; Vernau, Karen; Knipe, Marguerite; Hadji Rasouliha, Sheida; Drögemüller, Cord; Leeb, Tosso; Maciejczyk, Kimberly; Jenkins, Christopher A; Mellersh, Cathryn; Bannasch, Danika (2019). Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs. Genes, 10(6) MDPI, Molecular Diversity Preservation International 10.3390/genes10060435

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Two retrogenes on chromosomes 12 (12-RG) and 18 (18-RG) contribute to short-limbed phenotypes in dogs. 12-RG 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 ( = 569) were evaluated for age of onset, disc calcification, and genotypes for the retrogenes. Multivariable linear regression analysis identified the presence of one or two copies of 12-RG associated with significantly younger age at first surgery in a dominant manner. 18-RG had only a minor effect in dogs with one copy. Multivariable logistic regression showed that 12-RG had an additive effect on radiographic disc calcification, while 18-RG had no effect. Multivariable logistic regression using mixed breed cases and controls identified only 12-RG as highly associated with disc herniation in a dominant manner (Odds Ratio, OR, 18.42, 95% Confidence Interval (CI) 7.44 to 50.26; < 0.001). The relative risk for disc surgery associated with 12-RG 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Hadji Rasouliha, Sheida; Drögemüller, Cord; Leeb, Tosso and Bannasch, Danika

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

22 Jul 2019 14:34

Last Modified:

22 Oct 2019 23:30

Publisher DOI:

10.3390/genes10060435

PubMed ID:

31181696

Uncontrolled Keywords:

Canis lupus familiaris breed inherited intervertebral disc disease

BORIS DOI:

10.7892/boris.131371

URI:

https://boris.unibe.ch/id/eprint/131371

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