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Mammalian Genome

, Volume 7, Issue 11, pp 822–830 | Cite as

Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast/stem cell growth factor receptor

  • M. Johansson Moller
  • R. Chaudhary
  • E. Hellmén
  • B. Höyheim
  • B. Chowdhary
  • L. Andersson
Original Contributions

Abstract

Comparative mapping data suggested that the dominant white coat color in pigs may be due to a mutation in KIT which encodes the mast/stem cell growth factor receptor. We report here that dominant white pigs lack melanocytes in the skin, as would be anticipated for a KIT mutation. We found a complete association between the dominant white mutation and a duplication of the KIT gene, or part of it, in samples of unrelated pigs representing six different breeds. The duplication was revealed by single strand conformation polymorphism (SSCP) analysis and subsequent sequence analysis howing that white pigs transmitted two nonallelic KIT sequences. Quantitative Southern blot and quantitative PCR analysis, as well as fluorescence in situ hybridization (FISH) analysis, confirmed the presence of a gene duplication in white pigs. FISH analyses showed that KIT and the very closely linked gene encoding the platelet-derived growth factor receptor (PDG-FRA) are both located on the short arm of Chromosome (Chr) 8 at band 8pl2. The result revealed an extremely low rate of recombination in the centromeric region of this chromosome, since the closely linked (0.5 cM) serum albumin (ALB) locus has previously been in situ mapped to the long arm (8ql2). Pig Chr 8 shares extensive conserved synteny with human Chr 4, but the gene order is rearranged.

Keywords

Hair Follicle Hair Bulb Founder Animal Colored Animal Cell Growth Factor Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams, M.D. et al. (1995). Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature Suppl. 3-174.Google Scholar
  2. Andersson, L., Haley, C.S., Ellegren, H., Knott, S.A., Johansson, M., Andersson, K., Andersson-Eklund, L., Edfors-Lilja, I., Fredholm, M., Hansson, I., Håkansson, J., Lundström, K. (1994). Genetic mapping of quantitative trait loci for growth and fatness in pigs. Science 263, 1771–1774.PubMedCrossRefGoogle Scholar
  3. Andersson, L., Johansson, M., Wales, R., Siggens, K., Plastow, G. (1995). Genetic markers for pig coat colour. UK Patent Application No. 9515385.4.Google Scholar
  4. André, C, Martin, E., Cornu, F., Hu., W.-X., Wang, X.-P., Galibert, F. (1992). Genomic organisation of the human c-KITgene: evolution of the receptor tyrosine kinase subclass III. Oncogene 7, 685–691.PubMedGoogle Scholar
  5. Archibald, A.L., Haley, C.S., Brown, J.F., Couperwhite, S., Mcqueen, H.A., Nicholson, D., Coppieters, W., Van De Weghe, A., Stratil, A., Winterø, A.K., Fredholm, M., Larsen, N.J., Nielsen, V.H., Milan, D., Woloszyn, N., Robic, A., Dalens, M., Riquet, J., Gellin, J., Caritez, J.-C, Burgaud, G., Ollivier, L., Bidanel, J.-P., Vaiman, M., Renard, C, Gel-dermann, H., Davoli, R., Ruyter, D., Verstege, E.J., Groenen, M.A.M., Davies, W., Høyheim, B., Keiserud, A., Andersson, L., Ellegren, H., Johansson, M., Marklund, L., Miller, J.R., Andersson Dear, D.V., Signer, E., Jeffreys, A.J., Moran, C, Le Tissier, P., Muladno, Rothschild, M., Tuggle, C.K., Vaske, D., Helm, H., Liu, H.-C, Rahman, A., Yu, T.-P., Larson, R.G., Schmitz, C.B. (1995). The PiGMaP consortium linkage map of the pig (Sus Scrofa). Mamm. Genome 6, 157–175.PubMedCrossRefGoogle Scholar
  6. Chabot, B., Stephensson, D.A., Chapman, V.M., Besmer, P., Bernstein, A. (1988). The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 335, 88–89.PubMedCrossRefGoogle Scholar
  7. Chowdhary, B.P., Johansson, M., Chaudhary, R., Ellegren, H., Gu, F., Andersson, L., Gustavsson, I. (1993). In situ hybridization mapping and restriction fragment length polymorphism analysis of the porcine albumin (ALB) and transferrin (TF) genes. Anim. Genet. 24, 85–90.PubMedCrossRefGoogle Scholar
  8. Chowdhary, B.P., De La Sena, C, Harbitz, I., Eriksson, L., Gustavsson, I. (1995). FISH on metaphase and interphase chromosomes demonstrates the physical order of the genes for GPI, CRC and LIPE in pigs. Cytogenet. Cell Genet. 71, 175–178.PubMedCrossRefGoogle Scholar
  9. Claesson-Welsh, L., Eriksson, A., Westermark, B., Heldin, C.H. (1989). cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor established structural similarity to the B-type PDGF receptor. Proc. Natl. Acad. Sci. USA 86, 4917–4921.PubMedCrossRefGoogle Scholar
  10. Duttlinger, R., Manova, K., Chu, T.Y., Gyssler, C, Zelentz, A.D., Bachvarova, R.F., Besmer, P. (1993). W-sash affects positive and negative elements controlling c-kit expression: ectopic c-kit expression at sites of kit-ligand expression affects melanogenesis. Development 118, 705–717.PubMedGoogle Scholar
  11. Ellegren, H., Fredholm, M., Edfors-Lilja, I., Winterö, A.K., Andersson, L. (1993). Conserved synteny between pig chromosome 8 and human chromosome 4 but rearranged and distorted linkage maps. Genomics 17, 599–603.PubMedCrossRefGoogle Scholar
  12. Fleischman, R.A., Saltman, D.L., Stastny, V., Zneimer, S. (1991). Deletion of the c-kit protooncogene in the human developmental defect piebald trait. Proc. Natl. Acad. Sci. USA 88, 10885–10889.PubMedCrossRefGoogle Scholar
  13. Geissler, E.N., Mcfarland, E.C., Russell, E.S. (1980). Analysis of pleiotropism at the dominant white-spotting (W) locus of the house mouse: a description of ten new W alleles. Genetics 97, 337–361.Google Scholar
  14. Geissler, E.N., Ryan, M.A., Housman, D.E. (1988). The dominant white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell 55, 185–192.PubMedCrossRefGoogle Scholar
  15. Giebel, L.B., Spritz, R. (1991). Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism. Proc. Natl. Acad. Sci. USA 88, 8696–8699.PubMedCrossRefGoogle Scholar
  16. Giebel, L.B., Strunk, K.M., Holmes, S.A., Spritz, R. (1992). Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. Oncogene 7, 2207–2217.PubMedGoogle Scholar
  17. Green, P., Falls, K., Crooks, S. (1990). Documentation for CRI-MAP, version 2.4. Washington University School of Medicine, St Louis.Google Scholar
  18. Hetzer, H.O. (1948). Inheritance of coat color in swine. VII. Results of Landmce by Hampshire crosses. J. Hered. 39, 123–128.Google Scholar
  19. Higgins, D.G., Bleasby, A.J., Fuchs, R. (1992). CLUSTAL V: improved software for multiple sequence alignment. Comput. Appl. Biosci. 8, 189–191.PubMedGoogle Scholar
  20. Hultén, M.A., Palmer, R.W., Laurie, D.A. (1982). Chiasma derived genetic maps and recombination fractions: Chromosome 1. Ann. Hum. Genet. 46, 167–175.PubMedCrossRefGoogle Scholar
  21. Jackson, I.J. (1994). Molecular and developmental genetics of mouse coat color. Annu. Rev. Genet. 28, 189–217.PubMedCrossRefGoogle Scholar
  22. Johansson, M., Ellegren, H., Marklund, L., Gustavsson, U., Ringmar-Cederberg, E., Andersson, K., Edfors-Lilja, I., Andersson, L. (1992). The gene for dominant white color in the pig is closely linked to ALB AND PDGFRA on chromosome 8. Genomics 14, 965–969.PubMedCrossRefGoogle Scholar
  23. Johansson, M., Ellegren, H., Andersson, L. (1995). Comparative mapping reveals extensive linkage conservation—but with gene order rearrangements—between the pig and human genomes. Genomics 25, 682–690.PubMedCrossRefGoogle Scholar
  24. Lindsley, D.L., Sandler, L. (1977). The genetic analysis of meiosis in female Drosophila melanogaster. Philos. Trans. R. Soc. London B 277, 295–312.CrossRefGoogle Scholar
  25. Lord, E.A., Lumsden, J.M., Dodds, K.G., Henry, H.M., Crawford, A.M., Ansari, H.A., Pearce, P.D., Maher, D.W., Stone, R.T., Kappes, S.M., Beattie, C.W., Montgomery, G.W. (1996). The linkage map of sheep Chromosome 6 compared with orthologous regions in other species. Mamm. Genome, 7, 373–376.PubMedCrossRefGoogle Scholar
  26. Manova, K., Bachvarova, R.F. (1991). Expression of c-kit encoded at the W locus of mice in developing embryonic germ cells and presumptive melanoblasts. Dev. Biol. 146, 312–324.PubMedCrossRefGoogle Scholar
  27. Mariani, P., Johansson, M., Ellegren, H., Harbitz, I., Juneja, R.K., Andersson, L. (1992). Multiple restriction fragment length polymorphism in the porcine calcium release channel gene (CRC): assignment to the halothane (HAL) linkage group. Anim. Genet. 23, 185–190.Google Scholar
  28. Marklund, L., Johansson Moller, M., Höyheim, B., Davies, W., Fredholm, M., Juneja, R.K., Mariani, P., Coppieters, W., Ellegren, H., Andersson, L. (1996). A comprehensive linkage map of the pig based on a wild pig-Large White intercross. Anim. Genet., in press.Google Scholar
  29. Mayer, T.C., Green, M.C. (1968). An experimental analysis of the pigment defect caused by mutations at the W and Sl loci in mice. Dev. Biol. 18, 62–75.PubMedCrossRefGoogle Scholar
  30. Nocka, K., Tan, J.C., Chiu, E., Chu, T.Y., Ray, P., Traktman, P., Besmer, P. (1990). Molecular bases of dominant negative and loss of function mutations at the murine c-fe/white spotting locus: W 37, W, W41 and W. EMBO J. 9, 1805–1813.PubMedGoogle Scholar
  31. O’Brien, S.J. (ed.) (1993). Genetic Maps, 6th ed. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press).Google Scholar
  32. Ollivier, L., Sellier, P. (1982). Pig genetics: a review. Ann. Génét. Sél. Anim. 14, 481–544.Google Scholar
  33. Pawson, T., Bernstein, A. (1990). Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends Genet. 6, 350–356.PubMedCrossRefGoogle Scholar
  34. Rettenberger, G., Klett, C, Zechner, U., Kunz, J., Vogel, W., Hameister, H. (1995). Visualization of the conservation of synteny between humans and pigs by heterologous chromosome painting. Genomics 26, 372–378.PubMedCrossRefGoogle Scholar
  35. Searle, A.G. (1968). Comparative Genetics of Coat Colour in Mammals. (London: Logos Press Limited).Google Scholar
  36. Searle, A.G., Truslove, G.M. (1970). A gene triplet in the mouse. Genet. Res. 15, 227–235.PubMedCrossRefGoogle Scholar
  37. Schleuning, W.D., Medcalf, R.L., Hession, C, Rothenbuhler, R., Shaw, A., Kruithof, E.K. (1987). Plasminogen activator inhibitor 2: regulation of gene transcription during phorbol ester-mediated differentiation of U-937 human histiocytic lymphoma cells. Mol. Cell. Biol. 7, 4564–4567.PubMedGoogle Scholar
  38. Spillman, W.J. (1906). Inheritance of coat colour in swine. Science 24, 441–443.PubMedCrossRefGoogle Scholar
  39. Spritz, R. (1994). Molecular basis of human piebaldism. J. Invest. Dermatol. 103, 137–140.CrossRefGoogle Scholar
  40. Walhs, J.B. (1987). Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion? Genetics 117, 543–557.Google Scholar
  41. Wiseman, J. (1986). A History of the British Pig. (Worcester, UK: Ebenezer Baylis & Son Limited).Google Scholar
  42. Zeuner, F.E. (1963). A History of Domesticated Animals. (Essex, UK: Hutchinson & Co. Ltd, The Anchor Press).Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • M. Johansson Moller
    • 1
  • R. Chaudhary
    • 1
  • E. Hellmén
    • 2
  • B. Höyheim
    • 3
  • B. Chowdhary
    • 1
  • L. Andersson
    • 1
  1. 1.Department of Animal Breeding and GeneticsSwedish University of Agricultural Sciences, BMCUppsalaSweden
  2. 2.Department of PathologySwedish University of Agricultural SciencesUppsalaSweden
  3. 3.Department of Biochemistry, Physiology and NutritionNorwegian College of Veterinary MedicineOsloNorway

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