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PLoS genetics2013; 9(2); e1003248; doi: 10.1371/journal.pgen.1003248

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

Abstract: 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.
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Publication Date: 2013-02-07 PubMed ID: 23408897PubMed Central: PMC3567150DOI: 10.1371/journal.pgen.1003248Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research studies the complex inheritance patterns related to melanoma and pigmentation changes in Grey horses. It suggests that a single mutation plays a significant role in various traits that, traditionally, are considered complex and influenced by numerous genes.

Sample and Research Details

  • The researchers focused on a study involving 1,119 Grey horses across six countries over a nine-year period. These traits under scrutiny were the level of greying, the grade of melanoma, the degree of vitiligo, and the grade of speckling.
  • The study concentrated primarily on 3 genes: STX17, responsible for the greying phenotype; ASIP, associated with color variation; and POLY, a non-specific gene-related parameter.

Observation and Results

  • The gene termed STX17 was found to be of great influence on all observed traits, implying that a single mutation might have a considerable impact on characteristics considered genetically complex.
  • The researchers observed a high degree of ‘heritability’—the measure of the genetic contribution to the observed difference or variance—for traits like greying, vitiligo, and speckling. For melanoma, heritability was relatively moderate.
  • The additive impact of the ASIP gene was found to be significant only for melanoma.
  • The research found moderate to high genetic correlations among the traits, mostly influenced by the STX17 gene.

Conclusions

  • The findings of the study challenge the traditional conception that complex traits are influenced by a large pool of genes. It suggests that these can instead be influenced by a single mutation with significant effects.
  • The mutation in the STX17 gene can largely explain the moderate to high genetic correlations among the traits, showing strong ‘pleiotropic’ effects—a single gene influencing multiple unrelated traits.

Cite This Article

APA
Curik I, Druml T, Seltenhammer M, Sundström E, Pielberg GR, Andersson L, Sölkner J. (2013). Complex inheritance of melanoma and pigmentation of coat and skin in Grey horses. PLoS Genet, 9(2), e1003248. https://doi.org/10.1371/journal.pgen.1003248

Publication

PLoS genetics
ISSN: 1553-7404
NlmUniqueID: 101239074
Country: United States
Language: English
Volume: 9
Issue: 2
Pages: e1003248
PII: e1003248

Researcher Affiliations

Curik, Ino
  • Department of Animal Science, Faculty of Agriculture, University of Zagreb, Zagreb, Croatia. icurik@agr.hr
Druml, Thomas
    Seltenhammer, Monika
      Sundström, Elisabeth
        Pielberg, Gerli Rosengren
          Andersson, Leif
            Sölkner, Johann

              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

              Conflict of Interest Statement

              The authors have declared that no competing interests exist.

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              Citations

              This article has been cited 25 times.
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