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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Batcher et al. Genes-10-00435.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview |
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) |
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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, 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: |
05 Dec 2022 15:29 |
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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