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Background  The “rat-tail” syndrome (RTS) is an inherited hypotrichosis in cattle, which is exclusively expressed in diluted coloured hair. The affected animals also suffer from disturbed thermoregulation, which impairs their health and growth performance. Phenotypic features that are similar to RTS are observed in dogs with black hair follicle dysplasia.    Results  We used a resource cross population between German Holstein and Charolais cattle breeds to prove that epistatic interactions between at least three independent genetic loci are required for the expression of the RTS phenotype. In this population, the RTS is exclusively expressed in animals with a eumelanic background that is due to the dominant  E  D  allele at the  melanocortin 1 receptor  gene located on  Bos taurus  autosome (BTA) 18. In addition, only the individuals that are heterozygous at the  dilution  locus on BTA5 that corresponds to the  premelanosome protein  or  silver  gene variant  c.64G > A  were classified as displaying a RTS phenotype. Linkage and whole-genome association analyses using different models and different pedigrees allowed us to map a third locus (hereafter referred to as the  RTS  locus) that is essential for the expression of the RTS phenotype to the chromosomal region between 14 and 22 Mb on BTA5. Our findings clearly demonstrate that the  RTS  and  dilution  loci are distinct loci on BTA5.    Conclusions  Our study provides evidence that the  RTS  locus has effects on hair conformation and coat colour dilution and that the effect on coat colour dilution is clearly independent from that of the  dilution  locus. Finally, our results excluded several other loci that were previously reported to be associated with or to underlie hair conformation or pigmentation traits as the causal mutations of RTS and also several major functional candidate genes that are associated with hypotrichosis in humans. Our finding on the identification of a three-locus interaction that underlies RTS provides a prime example of epistatic interaction between several independent loci that is required for the expression of a distinct phenotype.    Electronic supplementary material  The online version of this article (doi:10.1186/s12711-016-0199-8) contains supplementary material, which is available to authorized users.

Epistatic interactions between at least three loci determine the “rat-tail” phenotype in cattle