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Curly coat represents an extraordinary type of coat in horses, particularly seen in American Bashkir Curly Horses and Missouri Foxtrotters. In some horses with curly coat, a hypotrichosis of variable extent was observed, making the phenotype appear more complex. In our study, we aimed at investigating the genetic background of curly coat with and without hypotrichosis using high density bead chip genotype and next generation sequencing data. Genome-wide association analysis detected significant signals (p = 1.412 × 10 −05 –1.102 × 10 −08 ) on horse chromosome 11 at 22–35 Mb. In this significantly associated region, six missense variants were filtered out from whole-genome sequencing data of three curly coated horses of which two variants within  KRT25  and  SP6  could explain all hair phenotypes. Horses heterozygous or homozygous only for  KRT25  variant showed curly coat and hypotrichosis, whereas horses with  SP6  variant only, exhibited curly coat without hypotrichosis. Horses with mutant alleles in both variants developed curly hair and hypotrichosis. Thus, mutant  KRT25  allele is masking  SP6  allele effect, indicative for epistasis of  KRT25  variant over SP6 variant. In summary, genetic variants in two different genes,  KRT25  and  SP6 , are responsible for curly hair. All horses with  KRT25  variant are additionally hypotrichotic due to the  KRT25  epistatic effect on  SP6 .

An epistatic effect of KRT25 on SP6 is involved in curly coat in horses