{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:53:48Z","timestamp":1791644028755,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maxine Adler Endowed Chair Funds","award":["na"],"award-info":[{"award-number":["na"]}]},{"name":"Poodle Club of America Foundation","award":["na"],"award-info":[{"award-number":["na"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/genes10060435","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T11:35:05Z","timestamp":1559907305000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-1130","authenticated-orcid":false,"given":"Kevin","family":"Batcher","sequence":"first","affiliation":[{"name":"Department of Population Health and Reproduction, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-2653","authenticated-orcid":false,"given":"Michelle","family":"Giuffrida","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly","family":"Sturges","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vernau","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marguerite","family":"Knipe","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheida Hadji","family":"Rasouliha","sequence":"additional","affiliation":[{"name":"Institute of Genetics, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-522X","authenticated-orcid":false,"given":"Cord","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Genetics, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Maciejczyk","sequence":"additional","affiliation":[{"name":"Department of Population Health and Reproduction, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9082-4270","authenticated-orcid":false,"given":"Christopher A.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Kennel Club Genetics Centre, Animal Health Trust, Kentford, Newmarket, Suffolk CB8 7UU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn","family":"Mellersh","sequence":"additional","affiliation":[{"name":"Kennel Club Genetics Centre, Animal Health Trust, Kentford, Newmarket, Suffolk CB8 7UU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-7207","authenticated-orcid":false,"given":"Danika","family":"Bannasch","sequence":"additional","affiliation":[{"name":"Department of Population Health and Reproduction, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11476","DOI":"10.1073\/pnas.1709082114","article-title":"FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs","volume":"114","author":"Brown","year":"2017","journal-title":"Proc. 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