Bovine Polledness – An Autosomal Dominant Trait with Allelic Heterogeneity Ivica Medugorac1*, Doris Seichter2, Alexander Graf3, Ingolf Russ2, Helmut Blum3, Karl Heinrich Go¨ pel4, Sophie Rothammer1, Martin Fo¨ rster1, Stefan Krebs3 1 Ludwig-Maximilians-University Munich, Munich, Germany, 2 Tierzuchtforschung e.V. Mu¨ nchen, Grub, Germany, 3 Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-University Munich, Munich, Germany, 4 Go¨ pel Genetik GmbH, Herleshausen, Germany Abstract The persistent horns are an important trait of speciation for the family Bovidae with complex morphogenesis taking place briefly after birth. The polledness is highly favourable in modern cattle breeding systems but serious animal welfare issues urge for a solution in the production of hornless cattle other than dehorning. Although the dominant inhibition of horn morphogenesis was discovered more than 70 years ago, and the causative mutation was mapped almost 20 years ago, its molecular nature remained unknown. Here, we report allelic heterogeneity of the POLLED locus. First, we mapped the POLLED locus to a ,381-kb interval in a multi-breed case-control design. Targeted re-sequencing of an enlarged candidate interval (547 kb) in 16 sires with known POLLED genotype did not detect a common allele associated with polled status. In eight sires of Alpine and Scottish origin (four polled versus four horned), we identified a single candidate mutation, a complex 202 bp insertion-deletion event that showed perfect association to the polled phenotype in various European cattle breeds, except Holstein-Friesian. The analysis of the same candidate interval in eight Holsteins identified five candidate variants which segregate as a 260 kb haplotype also perfectly associated with the POLLED gene without recombination or interference with the 202 bp insertion-deletion. We further identified bulls which are progeny tested as homozygous polled but bearing both, 202 bp insertion-deletion and Friesian haplotype. The distribution of genotypes of the two putative POLLED alleles in large semi-random sample (1,261 animals) supports the hypothesis of two independent mutations. Citation: Medugorac I, Seichter D, Graf A, Russ I, Blum H, et al. (2012) Bovine Polledness – An Autosomal Dominant Trait with Allelic Heterogeneity. PLoS ONE 7(6): e39477. doi:10.1371/journal.pone.0039477 Editor: Shuhong Zhao, Huazhong Agricultural University, China Received February 21, 2012; Accepted May 25, 2012; Published June 21, 2012 Copyright: 2012 Medugorac et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the German Research Foundation (DFG; Germany, ME 3404/2-1) and a grant from the German agriculture network PH A¨NOMICS (funded by Federal Ministry of Education and Research funding reference number 0315536F) as well as by substantial budget funds from the Chair of Animal Genetics and Husbandry of the Ludwig-Maximilians-University Munich (TierALL, LMU Munich, Germany), the Laboratory for Functional Genome Analysis (LAFUGA, Gene Center, LMU Munich, Germany) and the Tierzuchtforschung e.V. M u¨nchen (TZF Grub, Germany). The authors IM, SR, MF, SK, AG, HB, DS and IR are employed by TierALL, LAFUGA and TZF which supported this study by substantial budget funds but only the authors and not the funders had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have read the journal’s policy and declare the following conflicts: Karl Heinrich Go¨ pel, one of the co-authors, is employed by Go¨ pel Genetik GmbH, a commercial company that kindly provided a significant amount of samples and phenotypic information. However no funding was provided by Go¨ pel Genetik GmbH or other cattle breeding companies, or cattle breeders. In addition, neither cattle breeding companies nor cattle breeders were involved in the study design, analysis and interpretation of data, writing of the paper, or decision to submit for publication. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials. * E-mail: ivica.medjugorac@gen.vetmed.uni-muenchen.de Introduction Since the beginning of animal husbandry, humans have tended to accumulate particular variations in domesticated animals. Thereby, the variants of practical interest for agriculture were selected as well as phenotypes that visibly distinguished particular animals. This practice was more frequent in pets (e.g. cats and dogs) but led to the fixation of some obvious breed characteristics in cattle, too [1]. The absence of horns (polled phenotype) as well as horn shape diversity represents such evident traits in cattle. The persistent horn of the Bovidae consists of a pneumatised osseous core, which is fused with the frontal bone and covered by a cornified epithelium that grows outward from the skin at the base of the horn, thereby forming the cavernous visible horn. The development of horns is dependent on a number of different tissues and their interaction [2,3]. Before the domestication of cattle, horns were important for the survival of the wild species. Even after domestication, horns were a desired trait (e.g. fixation and use as draught animals) in most cattle breeding areas until recently. Exceptions to that rule are found in some regions (e.g. Scotland and the Nordic countries) where polledness was a desired trait much earlier probably due to dense housing of animals during the long winter. Nowadays, commercial dairy or beef herds are mainly confined to barns or fenced-in enclosures such as pastures or corrals. Under these conditions horns are not only of little value but can lead to considerable economic loss due to a higher risk of injuries and the possible consequences (infection, carcass deteri- oration etc.). Therefore in modern cattle husbandry removing horns at an early age has become an accepted management practice. However, all used methods are debatable not least because of animal welfare implications [4]. Hence, breeding polled cattle may constitute a non-invasive option to replace the common practice by means of genetic selection. PLoS ONE | www.plosone.org 1 June 2012 | Volume 7 | Issue 6 | e39477