The 80-kb DNA duplication on BTA1 is the only remaining candidate mutation for the polled phenotype of Friesian origin

Abstract

BackgroundThe absence of horns, called polled phenotype, is the favored trait in modern cattle husbandry. To date, polled cattle are obtained primarily by dehorning calves. Dehorning is a practice that raises animal welfare issues, which can be addressed by selecting for genetically hornless cattle. In the past 20 years, there have been many studies worldwide to identify unique genetic markers in complete association with the polled trait in cattle and recently, two different alleles at the POLLED locus, both resulting in the absence of horns, were reported: (1) the Celtic allele, which is responsible for the polled phenotype in most breeds and for which a single candidate mutation was detected and (2) the Friesian allele, which is responsible for the polled phenotype predominantly in the Holstein-Friesian breed and in a few other breeds, but for which five candidate mutations were identified in a 260-kb haplotype. Further studies based on genome-wide sequencing and high-density SNP (single nucleotide polymorphism) genotyping confirmed the existence of the Celtic and Friesian variants and narrowed down the causal Friesian haplotype to an interval of 145 kb.ResultsAlmost 6000 animals were genetically tested for the polled trait and we detected a recombinant animal which enabled us to reduce the Friesian POLLED haplotype to a single causal mutation, namely a 80-kb duplication. Moreover, our results clearly disagree with the recently reported perfect co-segregation of the POLLED mutation and a SNP at position 1 390 292 bp on bovine chromosome 1 in the Holstein-Friesian population.ConclusionWe conclude that the 80-kb duplication, as the only remaining variant within the shortened Friesian haplotype, represents the most likely causal mutation for the polled phenotype of Friesian origin.

Understanding the effects of the bovine POLLED variants

“…First identified in Holstein‐Friesian cattle, the Friesian POLLED variant is approximately 200 kb downstream of the Celtic variant and is an 80 128 bp duplication of the sequence between 1 909 352 and 1 989 480 bp (Fig. ) (Medugorac et al ; Allais‐Bonnet et al ; Rothammer et al ). The duplicated segment is located immediately after the original sequence and is in the same orientation.…”

“…Further research confirmed that this variant segregated in polled Holsteins that did not carry the Celtic POLLED allele (Wiedemar et al ). As with the Celtic POLLED variant, the Friesian POLLED variant does not disrupt any known coding sequence, splice site or intronic region, or any known regulatory regions (Rothammer et al ).…”

“…The POLLED genetic locus for cattle was first localised to bovine chromosome 1 (BTA1) by linkage mapping (Georges et al 1993), and the position was later refined to the centromeric region in several studies (Schmutz et al 1995;Brenneman et al 1996;Harlizius et al 1997). Four DNA sequence variants have subsequently been identified on BTA1 that are associated with the polled phenotype: Celtic POLLED (P C ), Friesian POLLED (P F ), Mongolian POLLED (P M ), and Guarani POLLED (P G ) (Medugorac et al 2012;Allais-Bonnet et al 2013;Rothammer et al 2014;Medugorac et al 2017;Utsunomiya et al 2019). All known variants are dominant, and cattle carrying a single POLLED variant will be either polled or scurred, depending on their genotype at the SCURS loci.…”

Management of Mendelian Traits in Breeding Programs by Gene Editing: A Simulation Study

“…In this simulation, a single locus was assumed to control polledness, but in reality the polled locus is more complex than HH3 and has at least two mutations on BTA1 that result in hornless cattle [36,37]. All gene-editing methods resulted in significant rates of allele frequency change (Table 4), with rates of change increasing with the efficiency of the technology (Fig.…”

Genotypes and allele frequencies of buried SNPs in a bovine single‐nucleotide polymorphism array in Japanese Black cattle

“…Polledness in cattle is an autosomal dominant trait; however, all heterozygotes had horns in this study. Although the polledness allele was repeatedly mapped to BTA1 in several cattle breeds (Georges et al, 1993;Harlizius, Tammen, Eichler, Eggen, & Hetzel, 1997;Medugorac et al, 2012;Nicholas, 2015;Rothammer et al, 2014;Schmutz, Marquess, Berryere, & Moker, 1995), the causative allele of the functional gene in the region remains unknown (Nicholas, 2015); thus future studies on the risk allele are required to determine whether the SNP was associated with polledness in Japanese Black cattle. The genomic position contained in both position-unassigned and assigned SNP respectively.…”