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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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.
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.
Andersson, L., Johansson, M., Wales, R., Siggens, K., Plastow, G. (1995). Genetic markers for pig coat colour. UK Patent Application No. 9515385.4.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Green, P., Falls, K., Crooks, S. (1990). Documentation for CRI-MAP, version 2.4. Washington University School of Medicine, St Louis.
Hetzer, H.O. (1948). Inheritance of coat color in swine. VII. Results of Landmce by Hampshire crosses. J. Hered. 39, 123–128.
Higgins, D.G., Bleasby, A.J., Fuchs, R. (1992). CLUSTAL V: improved software for multiple sequence alignment. Comput. Appl. Biosci. 8, 189–191.
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.
Jackson, I.J. (1994). Molecular and developmental genetics of mouse coat color. Annu. Rev. Genet. 28, 189–217.
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.
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.
Lindsley, D.L., Sandler, L. (1977). The genetic analysis of meiosis in female Drosophila melanogaster. Philos. Trans. R. Soc. London B 277, 295–312.
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.
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.
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.
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.
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.
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.
O’Brien, S.J. (ed.) (1993). Genetic Maps, 6th ed. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press).
Ollivier, L., Sellier, P. (1982). Pig genetics: a review. Ann. Génét. Sél. Anim. 14, 481–544.
Pawson, T., Bernstein, A. (1990). Receptor tyrosine kinases: genetic evidence for their role in Drosophila and mouse development. Trends Genet. 6, 350–356.
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.
Searle, A.G. (1968). Comparative Genetics of Coat Colour in Mammals. (London: Logos Press Limited).
Searle, A.G., Truslove, G.M. (1970). A gene triplet in the mouse. Genet. Res. 15, 227–235.
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.
Spillman, W.J. (1906). Inheritance of coat colour in swine. Science 24, 441–443.
Spritz, R. (1994). Molecular basis of human piebaldism. J. Invest. Dermatol. 103, 137–140.
Walhs, J.B. (1987). Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion? Genetics 117, 543–557.
Wiseman, J. (1986). A History of the British Pig. (Worcester, UK: Ebenezer Baylis & Son Limited).
Zeuner, F.E. (1963). A History of Domesticated Animals. (Essex, UK: Hutchinson & Co. Ltd, The Anchor Press).
Author information
Authors and Affiliations
Additional information
Accession numbers at EMBL of the two porcine KIT sequences: KIT1: X93082; KIT2: X93083.
Rights and permissions
About this article
Cite this article
Moller, M.J., Chaudhary, R., Hellmén, E. et al. Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast/stem cell growth factor receptor. Mammalian Genome 7, 822–830 (1996). https://doi.org/10.1007/s003359900244
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900244