{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:25:53Z","timestamp":1792027553606,"version":"4.4.0"},"reference-count":18,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016512","name":"Center for Companion Animal Health","doi-asserted-by":"publisher","award":["2019-7F"],"award-info":[{"award-number":["2019-7F"]}],"id":[{"id":"10.13039\/100016512","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009070","name":"Hans Sigrist Foundation","doi-asserted-by":"publisher","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}],"id":[{"id":"10.13039\/100009070","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Maxine Adler Endowed Chair funds","award":["No Grant number"],"award-info":[{"award-number":["No Grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Two FGF4 retrogenes (FGF4L1 on chromosome 18 and FGF4L2 on chromosome 12) have been identified to cause dwarfism across many dog breeds. Some breeds are nearly homozygous for both retrogenes (e.g., Dachshunds) and others are homozygous for just one (e.g., Beagles and Scottish Terriers). Since most breeds do not segregate both of these retrogenes, it is challenging to evaluate their individual effects on long bone length and body size. We identified two dog breeds selected for hunting ability, the Alpine Dachsbracke and the Schweizer Niederlaufhund, that segregate both of these retrogenes. Using individual measurements of height at the shoulder, back length, head width, thorax depth and width, and thoracic limb measurements, we evaluated the combined effects of FGF4 retrogenes within these breeds. We applied multivariable linear regression analysis to determine the effects of retrogene copy numbers on the measurements. Copy numbers of both retrogenes had significant effects reducing height at the shoulders and antebrachial length, with FGF4L1 having a much greater effect than FGF4L2. FGF4L1 alone influenced the degree of carpal valgus and FGF4L2 alone increased head width. Neither retrogene had an effect on thorax width or depth. Selectively breeding dogs with FGF4L1 and without FGF4L2 would likely lead to a reduction in the FGF4L2-related risk of intervertebral disc herniation while maintaining the reduction in leg length resulting from FGF4L1.<\/jats:p>","DOI":"10.3390\/genes13020325","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:37:46Z","timestamp":1644547066000},"page":"325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Effects of FGF4 Retrogenes on Canine Morphology"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7614-7207","authenticated-orcid":false,"given":"Danika","family":"Bannasch","sequence":"first","affiliation":[{"name":"Department of Population Health and Reproduction, University of California\u2014Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-1130","authenticated-orcid":false,"given":"Kevin","family":"Batcher","sequence":"additional","affiliation":[{"name":"Department of Population Health and Reproduction, University of California\u2014Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Leuthard","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bannasch","sequence":"additional","affiliation":[{"name":"Veterinary Center for Clinical Trials, School of Veterinary Medicine, University of California\u2014Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Hug","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-5928","authenticated-orcid":false,"given":"Denis J.","family":"Marcellin-Little","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California\u2014Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0037-2619","authenticated-orcid":false,"given":"Peter J.","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Department of Surgical and Radiological Sciences, University of California\u2014Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, 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, Vetsuisse Faculty, 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, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"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. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1126\/science.1173275","article-title":"An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs","volume":"325","author":"Parker","year":"2009","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0092-8674(94)90302-6","article-title":"Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia","volume":"78","author":"Shiang","year":"1994","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1073\/pnas.94.5.1872","article-title":"Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons","volume":"94","author":"Jurka","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/wdev.176","article-title":"The Fibroblast Growth Factor signaling pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Batcher, K., Dickinson, P., Maciejczyk, K., Brzeski, K., Rasouliha, S.H., Letko, A., Drogemuller, C., Leeb, T., and Bannasch, D. (2020). Multiple FGF4 Retrocopies Recently Derived within Canids. Genes, 11.","DOI":"10.3390\/genes11080839"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/ort.1952.23.suppl-11.01","article-title":"A pathologic-anatomical study on disc degeneration in dog: With special reference to the so-called enchondrosis intervertebralis","volume":"23","author":"Hansen","year":"1952","journal-title":"Acta Orthop. 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Biol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/325\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:30Z","timestamp":1760134650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/2\/325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,10]]},"references-count":18,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["genes13020325"],"URL":"https:\/\/doi.org\/10.3390\/genes13020325","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,10]]}}}