Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs
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...
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ftmdpi:oai:mdpi.com:/2073-4425/10/6/435/ 2023-08-20T04:05:48+02:00 Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs Kevin Batcher Peter Dickinson Michelle Giuffrida Beverly Sturges Karen Vernau Marguerite Knipe Sheida Hadji Rasouliha Cord Drögemüller Tosso Leeb Kimberly Maciejczyk Christopher A. Jenkins Cathryn Mellersh Danika Bannasch agris 2019-06-07 application/pdf https://doi.org/10.3390/genes10060435 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes10060435 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 10; Issue 6; Pages: 435 inherited intervertebral disc disease breed Canis lupus familiaris Text 2019 ftmdpi https://doi.org/10.3390/genes10060435 2023-07-31T22:20:32Z 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. Text Canis lupus MDPI Open Access Publishing Genes 10 6 435 |
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Open Polar |
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MDPI Open Access Publishing |
op_collection_id |
ftmdpi |
language |
English |
topic |
inherited intervertebral disc disease breed Canis lupus familiaris |
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inherited intervertebral disc disease breed Canis lupus familiaris Kevin Batcher Peter Dickinson Michelle Giuffrida Beverly Sturges Karen Vernau Marguerite Knipe Sheida Hadji Rasouliha Cord Drögemüller Tosso Leeb Kimberly Maciejczyk Christopher A. Jenkins Cathryn Mellersh Danika Bannasch Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs |
topic_facet |
inherited intervertebral disc disease breed Canis lupus familiaris |
description |
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. |
format |
Text |
author |
Kevin Batcher Peter Dickinson Michelle Giuffrida Beverly Sturges Karen Vernau Marguerite Knipe Sheida Hadji Rasouliha Cord Drögemüller Tosso Leeb Kimberly Maciejczyk Christopher A. Jenkins Cathryn Mellersh Danika Bannasch |
author_facet |
Kevin Batcher Peter Dickinson Michelle Giuffrida Beverly Sturges Karen Vernau Marguerite Knipe Sheida Hadji Rasouliha Cord Drögemüller Tosso Leeb Kimberly Maciejczyk Christopher A. Jenkins Cathryn Mellersh Danika Bannasch |
author_sort |
Kevin Batcher |
title |
Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs |
title_short |
Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs |
title_full |
Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs |
title_fullStr |
Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs |
title_full_unstemmed |
Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs |
title_sort |
phenotypic effects of fgf4 retrogenes on intervertebral disc disease in dogs |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2019 |
url |
https://doi.org/10.3390/genes10060435 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 10; Issue 6; Pages: 435 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes10060435 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes10060435 |
container_title |
Genes |
container_volume |
10 |
container_issue |
6 |
container_start_page |
435 |
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1774716548539219968 |