BMC genomics2012; 13; 365; doi: 10.1186/1471-2164-13-365

Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses.

Abstract: Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in STX17 to be associated with the phenotype. The aims of this study were to investigate if the duplication in Grey horses shows copy number variation and to exclude that any other polymorphism is uniquely associated with the Grey mutation. Results: We found little evidence for copy number expansion of the duplicated sequence in blood DNA from Grey horses. In contrast, clear evidence for copy number expansions was indicated in five out of eight tested melanoma tissues or melanoma cell lines. A tendency of a higher copy number in aggressive tumours was also found. Massively parallel resequencing of the ~350 kb Grey haplotype did not reveal any additional mutations perfectly associated with the phenotype, confirming the duplication as the true causative mutation. We identified three SNP alleles that were present in a subset of Grey haplotypes within the 350 kb region that shows complete linkage disequilibrium with the causative mutation. Thus, these three nucleotide substitutions must have occurred subsequent to the duplication, consistent with our interpretation that the Grey mutation arose more than 2,000 years before present. Conclusions: These results suggest that the mutation acts as a melanoma-driving regulatory element. The elucidation of the mechanistic features of the duplication will be of considerable interest for the characterization of these horse melanomas as well as for the field of human melanoma research.
Publication Date: 2012-08-02 PubMed ID: 22857264PubMed Central: PMC3443021DOI: 10.1186/1471-2164-13-365Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't


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 study investigates the presence of an expanded copy of a duplication specific to the STX17 gene in melanoma tissues from Grey horses. Grey horses specifically, exhibit aging-related greying, melanoma and vitiligo-like symptoms due to a 4.6 kb duplication in their STX17 gene. Blood DNA and melanoma tissues were used to show that this particular gene mutation drives the development of melanoma, and this finding can contribute to the field of human melanoma research.

Copy Number Variation in Grey Horses

  • The study aimed to find out if the duplication in STX17 in Grey horses shows copy number variation. Copy number variation refers to variations in the number of copies of a particular gene in the genome of an individual.
  • Another objective was to ensure that no other polymorphism was solely related to the Grey mutation. Polymorphism is the presence of genetic variation within a population, upon which natural selection can operate.
  • In blood DNA from Grey horses, there was little evidence for copy number expansion of the duplicated sequence.

Duplication Expansion in Melanoma Tissues

  • In contrast to the blood DNA, five out of the eight tested melanoma tissues or cell lines showed clear evidence of copy number expansions.
  • There was also an observed tendency of higher copy number in more aggressive tumours.

Resequencing of Grey Haplotype

  • The ~350 kb Grey haplotype was massively parallel re-sequenced, the process of sequencing DNA to detect mutations among other things.
  • It was confirmed that the Grey mutation is the true cause as no other mutations perfectly associated with the phenotype were found.
  • Three SNP alleles (variants of a gene) were present within the 350 kb region that shows complete linkage disequilibrium (non-random association) with the causative mutation.
  • These three nucleotide substitutions must have happened after the Grey mutation, further supporting the theory that the Grey mutation arose over 2000 years ago.

Conclusions and Further Research

  • The expansion of the duplication in the STX17 gene is suggested to act as a melanoma-driving regulatory element.
  • Understanding the mechanistic features of this duplication will be of considerable interest not only for characterizing these horse melanomas but also for human melanoma research.

Cite This Article

Sundstru00f6m E, Imsland F, Mikko S, Wade C, Sigurdsson S, Pielberg GR, Golovko A, Curik I, Seltenhammer MH, Su00f6lkner J, Lindblad-Toh K, Andersson L. (2012). Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses. BMC Genomics, 13, 365.


ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 13
Pages: 365

Researcher Affiliations

Sundstru00f6m, Elisabeth
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Imsland, Freyja
    Mikko, Sofia
      Wade, Claire
        Sigurdsson, Snaevar
          Pielberg, Gerli Rosengren
            Golovko, Anna
              Curik, Ino
                Seltenhammer, Monika H
                  Su00f6lkner, Johann
                    Lindblad-Toh, Kerstin
                      Andersson, Leif

                        MeSH Terms

                        • Alleles
                        • Animals
                        • Cell Line, Tumor
                        • DNA / blood
                        • DNA / metabolism
                        • DNA Copy Number Variations / genetics
                        • Gene Duplication
                        • Genome
                        • Genotype
                        • Haplotypes
                        • Horses / genetics
                        • Horses / metabolism
                        • Melanoma / genetics
                        • Melanoma / metabolism
                        • Melanoma / veterinary
                        • Phenotype
                        • Polymorphism, Single Nucleotide
                        • Qa-SNARE Proteins / genetics
                        • Qa-SNARE Proteins / metabolism
                        • Skin Neoplasms / genetics
                        • Skin Neoplasms / metabolism
                        • Skin Neoplasms / veterinary


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