Complex inheritance of melanoma and pigmentation of coat and skin in Grey horses

PLoS Genet. 2013;9(2):e1003248. doi: 10.1371/journal.pgen.1003248. Epub 2013 Feb 7.


The dominant phenotype of greying with age in horses, caused by a 4.6-kb duplication in intron 6 of STX17, is associated with a high incidence of melanoma and vitiligo-like skin depigmentation. However, the progressive greying and the incidence of melanoma, vitiligo-like depigmentation, and amount of speckling in these horses do not follow a simple inheritance pattern. To understand their inheritance, we analysed the melanoma grade, grey level, vitiligo grade, and speckling grade of 1,119 Grey horses (7,146 measurements) measured in six countries over a 9-year period. We estimated narrow sense heritability (h(2)), and we decomposed this parameter into polygenic heritability (h(2) (POLY)), heritability due to the Grey (STX17) mutation (h(2) (STX17)), and heritability due to agouti (ASIP) locus (h(2) (ASIP)). A high heritability was found for greying (h(2) = 0.79), vitiligo (h(2) = 0.63), and speckling (h(2) = 0.66), while a moderate heritability was estimated for melanoma (h(2) = 0.37). The additive component of ASIP was significantly different from zero only for melanoma (h(2) (ASIP) = 0.02). STX17 controlled large proportions of phenotypic variance (h(2) (STX17) = 0.18-0.55) and overall heritability (h(2) (STX17)/h(2) = 0.28-0.83) for all traits. Genetic correlations among traits were estimated as moderate to high, primarily due to the effects of the STX17 locus. Nevertheless, the correlation between progressive greying and vitiligo-like depigmentation remained large even after taking into account the effects of STX17. We presented a model where four traits with complex inheritance patterns are strongly influenced by a single mutation. This is in line with evidence of recent studies in domestic animals indicating that some complex traits are, in addition to the large number of genes with small additive effects, influenced by genes of moderate-to-large effect. Furthermore, we demonstrated that the STX17 mutation explains to a large extent the moderate to high genetic correlations among traits, providing an example of strong pleiotropic effects caused by a single gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Duplication
  • Genetic Pleiotropy
  • Horses / genetics*
  • Introns / genetics
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Melanoma* / veterinary
  • Mutation
  • Neoplasm Staging
  • Pigmentation / genetics*
  • Qa-SNARE Proteins* / genetics
  • Qa-SNARE Proteins* / metabolism
  • Skin / metabolism
  • Skin / pathology


  • Qa-SNARE Proteins

Grants and funding

This work was financially supported by the EU-INCO-Copernicus (Project IC15CT96-0904, “Biotechnical methods in the maintenance of the genetic diversity in the Lipizzan horse breed” led by Prof. Goffried Brem, University of Veterinary Medicine Vienna) from 1997 to 2000, the Croatian Ministry of Science, Education and Sports (Project 178-1780460-0546, “Strategies for elimination of genetic defects in selected populations”) from 2007 to 2012, the MOEL program of the “Österreichischen Forschungsgemeinschaft” in 2010, and the Swedish Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.