Topologically associating domains in the POLLED region are the same for Angus- and Brahman-specific Hi-C reads from F1 hybrid fetal tissue.

Horns, a form of headgear carried by Bovidae, have ethical and economic implications for ruminant production species such as cattle and goats. Hornless (polled) individuals are preferred. In cattle, four genetic variants (Celtic, Friesian, Mongolian and Guarani) are associated with the polled phenotype, which are clustered in a 300-kb region on chromosome 1. As the variants are intergenic, the functional effect is unknown. The aim of this study was to determine if the POLLED variants affect chromatin structure or disrupt enhancers using publicly available data. Topologically associating domains (TADs) were analyzed using Angus- and Brahman-specific Hi-C reads from lung tissue of an Angus (Celtic allele) cross Brahman (horned) fetus. Predicted bovine enhancers and chromatin immunoprecipitation sequencing peaks for histone modifications associated with enhancers (H3K27ac and H3K4me1) were mapped to the POLLED region. TADs analyzed from Angus- and Brahman-specific Hi-C reads were the same, therefore, the Celtic variant does not appear to affect this level of chromatin structure. The Celtic variant is located in a different TAD from the Friesian, Mongolian, and Guarani variants. Predicted enhancers and histone modifications overlapped with the Guarani and Friesian variants but not the Celtic or Mongolian variants. This study provides insight into the mechanisms of the POLLED variants for disrupting horn development. These results should be validated using data produced from the horn bud region of horned and polled bovine fetuses.

Understanding the effects of the bovine POLLED variants.

Horns are paired appendages on the head of bovine species, comprising an inner bony core and outer keratin sheath. The horn bud forms during early fetal development but ossification of the developing horn does not occur until approximately 1 month after birth. Little is known about the genetic pathways that lead to horn growth. Hornless, or polled, animals are found in all domestic bovids. Histological studies of bovine fetuses have shown that the horn bud does not form in polled individuals. There are currently four known genetic variants for polledness in cattle on BTA1. All of the variants are intergenic, but probably affect regulation of nearby genes or long non-coding RNAs. Transcriptomic studies suggest that the expression of two nearby long non-coding RNAs are affected by the Celtic POLLED variant, but further studies are required to confirm these data. Candidate genes located elsewhere in the genome are involved in regulating bone formation and epithelial-to-mesenchymal transition. Expression of one of these candidate genes, RXFP2, appears to be reduced in the fetal horn bud of polled animals carrying the Celtic variant compared with horned individuals. Investigating horn ontogenesis and the genetic pathway by which the POLLED variants prevent horn development has implications for cattle breeding. If the genetic basis of horn bud formation and polledness is better understood, then new targets may be identified for precision genome editing to create polled individuals.