Polled/Horns

Phene ID

828

Name

Polled/Horns

Phene Name

Haplotype BHP; Haplotype HHP; Haplotype JHP

OMIA ID

483

Species ID

9913

Characterised

Yes

Characterised Year

2012

The absence of horns (polledness) is of substantial benefit in cattle, from an economic and welfare point of view: bruising due to horns is eliminated, and the stress associated with de-horning is avoided. (Information complied by Ulrika Tjälldén and Vanja Kinch, Uppsala, March 1998). In addition to naturally occurring variants for this trait, variants have been created artificially: Genetically-modifed organism; GMO.

As described in the History section, this trait was the first cattle trait to be shown to be inherited in a Mendelian manner. This form of inheritance has been confirmed many times, e.g. Stookey and Goonewardene (1996). (Information complied by Ulrika Tjälldén and Vanja Kinch, Uppsala, March 1998); supplemented by FN 14th June 2013

Finally, after many frustrating years, mutations completely associated with the last of Bateson and Saunder's (1902) six initial Mendelian traits have been determined.
Resequencing (by Medugorac et al., 2012) of the region mapped by Seichter et al. (2012), and subsequent investigation of putative DNA sequence variants, revealed two alleles completely associated with polledness in cattle of European origin: a 202bp indel in breeds of “Celtic” origin (called P_C or (P_202ID)) and a 260kb haplotype block marked by two indels and three SNPs in cattle of Friesian origin (called P_F). Heterozygosity or homozygosity for either of these alleles, or heterozygosity for both alleles, is completely associated with polledness. Despite this major discovery by Medugorac et al. (2012), and as if to reinforce the intransigence of this iconic Mendelian trait, no gene can yet be named, because none of these mutations disrupts "any known coding sequence or a splice site, or an intronic region, or any known regulatory regions". We are still a long way from having a complete understanding of this enigmatic locus. Until then, in OMIA the polled "gene" is called POLLED.
Independent fine-mapping, followed by extensive sequencing in the candidate region, enabled Allais-Bonnet et al. (2013) to confirm their previously-reported "Celtic" (P_C) mutation, but to specify it slightly differently as "a duplication of 212 bp replacing a segment of 10 bp (g.1706051_1706060 delins 1705834_1706045 dup" (UMD3.1 bovine genome assembly) and to confirm that it occurs in a region with no known genes or expressed sequence tags. A similar approach enabled Allais-Bonne et al. (2013) to reduce the list of candidate mutations for the "Friesian" (P_F) allele to "three SNP (g.1764239T>C, g.1768587C>A, g.1855898G>A) and a large duplication of 80,128 bp (g.1909352_1989480dup)" (UMD3.1 bovine genome assembly), again in a region with no known genes or expressed sequence tags. Based on histological and gene-expression studies, Allais-Bonne et al. (2013) proposed that "the ectopic expression of a lincRNA in P_C/p horn buds as a probable cause of horn bud agenesis" and "provide[d] evidence for an involvement of OLIG2, FOXL2 and RXFP2 in horn bud differentiation, and draw a first link between bovine, ovine and caprine Polled loci."
The Holstein situation was further investigated by Glatzer et al. (2013), who reported "Sequencing of the positional candidate genes within the 1 Mb polled region and whole genome sequencing of Holsteins revealed a single nucleotide polymorphism (SNP) AC000158: g.1390292G>A within intron 3 of the interferon gamma receptor 2 gene (IFNGR2) in perfect co-segregation with polledness in Holsteins. This complete association was validated in 443 animals of the same breed." Interestingly, as also reported by Glatzer et al. (2013), in a selective-sweep study by Stella et al. (2010) "The SNP featuring the largest difference in allelic frequency between polled and horned animals was located within the interferon gamma receptor 2 gene (IFNGR2)".
Sequencing and additional genotyping enabled Wiedemar et al. (2014) to confirm the 212bp indel "Celctic" mutation P_C as causal for polled in Simmentals and other European beef breeds. They also "identified a total of 182 sequence variants as candidate mutations for polledness in Holstein cattle, including an 80 kb genomic duplication and three SNPs reported before [see above]." Also, the authors reported that "For the first time we showed that hornless cattle with scurs are obligate heterozygous for one of the polled mutations."
By testing almost 6000 cattle, Rothammer et al. (2014) confirmed the 80kb duplication mentioned above (now called P_80kbID) to be the "single causal mutation" in Holstein-Friesian cattle", i.e. to be P_F. In addition, their results did not support the SNP association reported by Glatzer et al. (2013).
By introgressing the P_C "allele into dairy cattle by genome editing [via TALEN-stimulated homology-dependent repair to produce four cell lines either homozygous or heterozygous for the P_C allele]", followed by reproductive cloning to produce five live calves (all lacking horn buds), two of which were polled at 10 months, Carlson et al. (2016) provided "the first empirical validation of a putative causative allele in livestock, and this report provides evidence that P_C, a sequence variant duplication of unknown function in a genomic region with no known or predicted coding or noncoding genes, is causative for polled." This study involved genetically modified organisms (GMO).
A third polled allele, the Mongolian allele, was discovered by Medugorac et al. (2017) in Mongolian Turano cattle. It is "a complex 219-bp duplication–insertion (P_219ID) beginning at 1,976,128 bp and a 7-bp deletion and 6-bp insertion (P_1ID) located 621 bp upstream of this position . . . . This rearrangement results in duplication of an 11-bp motif (5′-AAAGAAGCAAA-3′) that is entirely conserved among Bovidae . . . and that is also duplicated in the 80-kb duplication responsible for Friesian polledness". Intriguingly, this allele has been introgressed into yaks with which Mongolian Turano cattle have been herded for more than 1,500 years, via backcrossing female yak-cattle hybrids to male yaks (Medugorac et al., 2017). The suggested abbreviation for the Mongolian allele is P_M (FN, in consultation with A. Capitan and I. Medugorac) or P_219ID (Chen et al., 2017).
Utsunomiya et al. (2019) reported a "novel polled variant . . . [that they named] Guarani (P_G)", comprising a novel duplication the region BTA1: 1,893,790–2,004,553 in Nellore cattle.
Koufariotis et al. (2018) "provide[d] evidence that the polled mutation in Brahmans, a desirable trait under very strong recent selection, is of Celtic origin and is introgressed from Bos taurus."
By whole-genome sequencing with an Oxford Nanopore Technology's minION sequencer "four homozygous poll (PcPc), four homozygous horned (pp) and three heterozygous (Pcp) Brahmans" and comparing the sequence in the polled region, Lamb et al. (2020) confirmed that the polled allele in the Brahman breed is the Celtic allele.
Schuster et al. (2020): "For the generation of polled offspring from a horned Holstein–Friesian bull, we isolated the Polled Celtic variant from the genome of an Angus cow and integrated it into the genome of fibroblasts taken from the horned bull using the CRISPR/Cas12a system (formerly Cpf1). Modified fibroblasts served as donor cells for somatic cell nuclear transfer and reconstructed embryos were transferred into synchronized recipients. One resulting pregnancy was terminated on day 90 of gestation for the examination of the fetus. Macroscopic and histological analyses proved a polled phenotype. The remaining pregnancy was carried to term and delivered one calf with a polled phenotype which died shortly after birth." This study involved genetically modified organisms (GMO).