Novel Heredity Basis of the Four-Horn Phenotype in Sheep Using Genome-Wide Sequence Data.

Horns are an important breeding trait for sheep. However, no widely recognized viewpoint on the regulatory genes and mechanisms of horns is available, and the genetic basis of the four-horn phenotype (FHP) is unclear. This work conducted a genome-wide association study with 100 sheep genomes from multiple breeds to investigate the genetic basis of the FHP. The results revealed three significant associations (corrected as < 1.64 × 10) of the InDels (CHR2: g.133,742,709delA, g.133,743,215insC, and g.133,743,940delT) for FHP in the intergenic sequence (IGS) between the and the of CHR2. Moreover, 14 significant associations (corrected as < 1.42 × 10) of SNPs with the FHP phenotype were identified in CHR2 and CHR16, including five (e.g., CHR16: g.40,351,378G > A and g.40,352,577G > A) located in the intron of the gene, eight (e.g., CHR2: g.133,727,513C > T and g.133,732,145T > G) in the IGS between and , and only one (CHR2: g.133,930,761A > G) in the IGS between and . Obvious divergence was also observed in genotype patterns between the FHP and others (two horns and hornless) in the and gene regions. An extremely significant linkage also occurred between Loci I and Loci II within 100 individuals (LD = -156.02186, < 0.00001). In summary, our study indicated that the genomic sequences from CHR2 and CHR16 contributed to the FHP in sheep, specifically the key candidate genes and . These results improved our understanding of the Mendelian genetic basis of the FHP in sheep.