{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:09:51Z","timestamp":1790838591465,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Hereford Association","award":["130363"],"award-info":[{"award-number":["130363"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>In spring 2020, six Hereford calves presented with congenital facial deformities attributed to a condition we termed mandibulofacial dysostosis (MD). Affected calves shared hallmark features of a variably shortened and\/or asymmetric lower mandible and bilateral skin tags present 2\u201310 cm caudal to the commissure of the lips. Pedigree analysis revealed a single common ancestor shared by the sire and dam of each affected calf. Whole-genome sequencing (WGS) of 20 animals led to the discovery of a variant (Chr26 g. 14404993T&gt;C) in Exon 3 of CYP26C1 associated with MD. This missense mutation (p.L188P), is located in an \u03b1 helix of the protein, which the identified amino acid substitution is predicted to break. The implication of this mutation was further validated through genotyping 2 additional affected calves, 760 other Herefords, and by evaluation of available WGS data from over 2500 other individuals. Only the affected individuals were homozygous for the variant and all heterozygotes had at least one pedigree tie to the suspect founder. CYP26C1 plays a vital role in tissue-specific regulation of retinoic acid (RA) during embryonic development. Dysregulation of RA can result in teratogenesis by altering the endothelin-1 signaling pathway affecting the expression of Dlx genes, critical to mandibulofacial development. We postulate that this recessive missense mutation in CYP26C1 impacts the catalytic activity of the encoded enzyme, leading to excess RA resulting in the observed MD phenotype.<\/jats:p>","DOI":"10.3390\/genes11111246","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T20:51:00Z","timestamp":1603399860000},"page":"1246","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mandibulofacial Dysostosis Attributed to a Recessive Mutation of CYP26C1 in Hereford Cattle"],"prefix":"10.3390","volume":"11","author":[{"given":"Renae L.","family":"Sieck","sequence":"first","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Bedwell","sequence":"additional","affiliation":[{"name":"American Hereford Association, Breed Improvement, Kansas City, MO 64048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A.","family":"Ward","sequence":"additional","affiliation":[{"name":"American Hereford Association, Breed Improvement, Kansas City, MO 64048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy K.","family":"Sanders","sequence":"additional","affiliation":[{"name":"American Hereford Association, Breed Improvement, Kansas City, MO 64048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Hua","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sichong","family":"Peng","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\/0000-0001-5438-8555","authenticated-orcid":false,"given":"Jessica L.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5166-2296","authenticated-orcid":false,"given":"David J.","family":"Steffen","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s13258-017-0525-8","article-title":"Genetic disorders in beef cattle: A review","volume":"39","author":"Rutkowska","year":"2017","journal-title":"Genes Genom."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6693","DOI":"10.3168\/jds.2015-10517","article-title":"Identification of a nonsense mutation in APAF1 that is likely causal for a decrease in reproductive efficiency in Holstein dairy cattle","volume":"99","author":"Adams","year":"2016","journal-title":"J. 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