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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.

              References

              This article includes 39 references
              1. Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits.. Nat Rev Genet 2009 Apr;10(4):241-51.
                pubmed: 19293820doi: 10.1038/nrg2554google scholar: lookup
              2. Mackay TF, Stone EA, Ayroles JF. The genetics of quantitative traits: challenges and prospects.. Nat Rev Genet 2009 Aug;10(8):565-77.
                pubmed: 19584810doi: 10.1038/nrg2612google scholar: lookup
              3. Goddard ME, Hayes BJ. Mapping genes for complex traits in domestic animals and their use in breeding programmes.. Nat Rev Genet 2009 Jun;10(6):381-91.
                pubmed: 19448663doi: 10.1038/nrg2575google scholar: lookup
              4. Flint J, Mackay TF. Genetic architecture of quantitative traits in mice, flies, and humans.. Genome Res 2009 May;19(5):723-33.
                pmc: PMC3647534pubmed: 19411597doi: 10.1101/gr.086660.108google scholar: lookup
              5. Yang J, Benyamin B, McEvoy BP, Gordon S, Henders AK, Nyholt DR, Madden PA, Heath AC, Martin NG, Montgomery GW, Goddard ME, Visscher PM. Common SNPs explain a large proportion of the heritability for human height.. Nat Genet 2010 Jul;42(7):565-9.
                pmc: PMC3232052pubmed: 20562875doi: 10.1038/ng.608google scholar: lookup
              6. Kemper KE, Visscher PM, Goddard ME. Genetic architecture of body size in mammals.. Genome Biol 2012;13(4):244.
                pmc: PMC3446298pubmed: 22546202doi: 10.1186/gb4016google scholar: lookup
              7. Kemper KE, Goddard ME. Understanding and predicting complex traits: knowledge from cattle.. Hum Mol Genet 2012 Oct 15;21(R1):R45-51.
                pubmed: 22899652doi: 10.1093/hmg/dds332google scholar: lookup
              8. Rosengren Pielberg G, Golovko A, Sundström E, Curik I, Lennartsson J, Seltenhammer MH, Druml T, Binns M, Fitzsimmons C, Lindgren G, Sandberg K, Baumung R, Vetterlein M, Strömberg S, Grabherr M, Wade C, Lindblad-Toh K, Pontén F, Heldin CH, Sölkner J, Andersson L. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.. Nat Genet 2008 Aug;40(8):1004-9.
                pubmed: 18641652doi: 10.1038/ng.185google scholar: lookup
              9. Sundström E, Komisarczuk AZ, Jiang L, Golovko A, Navratilova P, Rinkwitz S, Becker TS, Andersson L. Identification of a melanocyte-specific, microphthalmia-associated transcription factor-dependent regulatory element in the intronic duplication causing hair greying and melanoma in horses.. Pigment Cell Melanoma Res 2012 Jan;25(1):28-36.
                pubmed: 21883983doi: 10.1111/j.1755-148x.2011.00902.xgoogle scholar: lookup
              10. Sundström E, Imsland F, Mikko S, Wade C, Sigurdsson S, Pielberg GR, Golovko A, Curik I, Seltenhammer MH, Sölkner J, Lindblad-Toh K, Andersson L. Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses.. BMC Genomics 2012 Aug 2;13:365.
                pmc: PMC3443021pubmed: 22857264doi: 10.1186/1471-2164-13-365google scholar: lookup
              11. Sponenberg DP. Equine Color Genetics. 2003.
              12. Curik I, Seltenhammer M, Sölkner J. Quantitative genetic analysis of melanoma and grey level in Lipizzan horses. Proceedings of the 7th World Congress on Genetics Applied to Livestock Production 2002;CD-ROM: Communication No. 05-09, August 19–23, Monpellier, France.
              13. Toth Z, Kaps M, Sölkner J, Bodo I, Curik I. Quantitative genetic aspects of coat color in horses.. J Anim Sci 2006 Oct;84(10):2623-8.
                pubmed: 16971562doi: 10.2527/jas.2005-704google scholar: lookup
              14. Foley GL, Valentine BA, Kincaid AL. Congenital and acquired melanocytomas (benign melanomas) in eighteen young horses.. Vet Pathol 1991 Sep;28(5):363-9.
                pubmed: 1750161doi: 10.1177/030098589102800503google scholar: lookup
              15. Pulley LT, Stannard AA. Tumors of the skin and soft tissues. Tumors in domestic animals 1990;pp. 75–82.
              16. Gorham S, Robl M. Melanoma in the grey horse: The darker side of equine aging. Vet Med 1986;81:446–448.
              17. Desser H, Niebauer GW, Gebhart W. [Polyamine and histamine contents in the blood of pigmented, depigmented and melanoma bearing Lipizzaner horses].. Zentralbl Veterinarmed A 1980 Feb;27(1):45-53.
                pubmed: 6774520
              18. Fleury C, Bérard F, Leblond A, Faure C, Ganem N, Thomas L. The study of cutaneous melanomas in Camargue-type gray-skinned horses (2): epidemiological survey.. Pigment Cell Res 2000 Feb;13(1):47-51.
                pubmed: 10761996doi: 10.1034/j.1600-0749.2000.130109.xgoogle scholar: lookup
              19. Valentine BA. Equine melanocytic tumors: a retrospective study of 53 horses (1988 to 1991).. J Vet Intern Med 1995 Sep-Oct;9(5):291-7.
                pubmed: 8531173doi: 10.1111/j.1939-1676.1995.tb01087.xgoogle scholar: lookup
              20. Rieder S, Stricker CH, Joerg H, Dummer R, Stranzinger G. A comparative genetic approach for the investigation of aging grey horse melanoma. J Anim Breed Genet 2000;117:73–82.
              21. Seltenhammer MH, Simhofer H, Scherzer S, Zechner R, Curik I, Sölkner J, Brandt SM, Jansen B, Pehamberger H, Eisenmenger E. Equine melanoma in a population of 296 grey Lipizzaner horses.. Equine Vet J 2003 Mar;35(2):153-7.
                pubmed: 12638791doi: 10.2746/042516403776114234google scholar: lookup
              22. Hann SK, Nordlund JJ. Vitiligo. 2000.
              23. Passeron T, Ortonne JP. Physiopathology and genetics of vitiligo.. J Autoimmun 2005;25 Suppl:63-8.
                pubmed: 16298511doi: 10.1016/j.jaut.2005.10.001google scholar: lookup
              24. Zhang XJ, Chen JJ, Liu JB. The genetic concept of vitiligo.. J Dermatol Sci 2005 Sep;39(3):137-46.
                pubmed: 16140217doi: 10.1016/j.jdermsci.2005.06.004google scholar: lookup
              25. Jin Y, Riccardi SL, Gowan K, Fain PR, Spritz RA. Fine-mapping of vitiligo susceptibility loci on chromosomes 7 and 9 and interactions with NLRP1 (NALP1).. J Invest Dermatol 2010 Mar;130(3):774-83.
                pmc: PMC3513759pubmed: 19727120doi: 10.1038/jid.2009.273google scholar: lookup
              26. Pirisi A. Vitiligo and melanoma-two sides of the same coin?. Lancet Oncol 2010;11:517.
              27. Jeon JT, Carlborg O, Törnsten A, Giuffra E, Amarger V, Chardon P, Andersson-Eklund L, Andersson K, Hansson I, Lundström K, Andersson L. A paternally expressed QTL affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus.. Nat Genet 1999 Feb;21(2):157-8.
                pubmed: 9988263doi: 10.1038/5938google scholar: lookup
              28. Van Laere AS, Nguyen M, Braunschweig M, Nezer C, Collette C, Moreau L, Archibald AL, Haley CS, Buys N, Tally M, Andersson G, Georges M, Andersson L. A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig.. Nature 2003 Oct 23;425(6960):832-6.
                pubmed: 14574411doi: 10.1038/nature02064google scholar: lookup
              29. Grisart B, Coppieters W, Farnir F, Karim L, Ford C, Berzi P, Cambisano N, Mni M, Reid S, Simon P, Spelman R, Georges M, Snell R. Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition.. Genome Res 2002 Feb;12(2):222-31.
                pubmed: 11827942doi: 10.1101/gr.224202google scholar: lookup
              30. Littlejohn M, Grala T, Sanders K, Walker C, Waghorn G, Macdonald K, Coppieters W, Georges M, Spelman R, Hillerton E, Davis S, Snell R. Genetic variation in PLAG1 associates with early life body weight and peripubertal weight and growth in Bos taurus.. Anim Genet 2012 Oct;43(5):591-4.
                pubmed: 22497486doi: 10.1111/j.1365-2052.2011.02293.xgoogle scholar: lookup
              31. Wiener P, Woolliams JA, Frank-Lawale A, Ryan M, Richardson RI, Nute GR, Wood JD, Homer D, Williams JL. The effects of a mutation in the myostatin gene on meat and carcass quality.. Meat Sci 2009 Sep;83(1):127-34.
                pubmed: 20416780doi: 10.1016/j.meatsci.2009.04.010google scholar: lookup
              32. Hayes BJ, Pryce J, Chamberlain AJ, Bowman PJ, Goddard ME. Genetic architecture of complex traits and accuracy of genomic prediction: coat colour, milk-fat percentage, and type in Holstein cattle as contrasting model traits.. PLoS Genet 2010 Sep 23;6(9):e1001139.
                doi: 10.1371/journal.pgen.1001139pmc: PMC2944788pubmed: 20927186google scholar: lookup
              33. Liu F, Wollstein A, Hysi PG, Ankra-Badu GA, Spector TD, Park D, Zhu G, Larsson M, Duffy DL, Montgomery GW, Mackey DA, Walsh S, Lao O, Hofman A, Rivadeneira F, Vingerling JR, Uitterlinden AG, Martin NG, Hammond CJ, Kayser M. Digital quantification of human eye color highlights genetic association of three new loci.. PLoS Genet 2010 May 6;6(5):e1000934.
                doi: 10.1371/journal.pgen.1000934pmc: PMC2865509pubmed: 20463881google scholar: lookup
              34. Protas ME, Patel NH. Evolution of coloration patterns.. Annu Rev Cell Dev Biol 2008;24:425-46.
                pubmed: 18593352doi: 10.1146/annurev.cellbio.24.110707.175302google scholar: lookup
              35. Fang M, Larson G, Ribeiro HS, Li N, Andersson L. Contrasting mode of evolution at a coat color locus in wild and domestic pigs.. PLoS Genet 2009 Jan;5(1):e1000341.
                doi: 10.1371/journal.pgen.1000341pmc: PMC2613536pubmed: 19148282google scholar: lookup
              36. Rieder S, Taourit S, Mariat D, Langlois B, Guérin G. Mutations in the agouti (ASIP), the extension (MC1R), and the brown (TYRP1) loci and their association to coat color phenotypes in horses (Equus caballus).. Mamm Genome 2001 Jun;12(6):450-5.
                pubmed: 11353392doi: 10.1007/s003350020017google scholar: lookup
              37. Gilmour AR, Gogel BJ, Cullis BR, Thompson R. ASReml User Guide Release 3.0. 2009.
              38. Mrode RA. Linear Models for the Prediction of Animal Breeding Values. 2005.
              39. Falconer DS, Mackay TFC. Introduction to quantitative genetics. 1996.

              Citations

              This article has been cited 25 times.
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