Investigation of KIT Gene Polymorphisms in Korean Cattle

  • Hoque, Md. Rashedul (Department of Animal Science and Biotechnology, Chungnam National University) ;
  • Lee, Seung-Hwan (Hanwoo Experiment Station, National Institute of Animal Science, R.D.A.) ;
  • Lim, Da-Jeong (Animal Genome and Bioinformatics Division, National Institute of Animal Science) ;
  • Cho, In-Cheol (National Institute of Animal Science, Rural Development Administration) ;
  • Choi, Nu-Ri (Department of Animal Science and Biotechnology, Chungnam National University) ;
  • Seo, Dong-Won (Department of Animal Science and Biotechnology, Chungnam National University) ;
  • Lee, Jun-Heon (Department of Animal Science and Biotechnology, Chungnam National University)
  • Received : 2012.09.25
  • Accepted : 2012.12.03
  • Published : 2012.12.31


KIT gene is the major causative gene for coat color variation in diverse animal species. This gene regulates melanocyte migration from the neural crest to target tissues and the mutation of this gene can affect dominant white phenotypes in animals. Because this gene has a major influence for the coat color variation, single nucleotide polymorphisms (SNPs) in 14 Korean cattle (Hanwoo) and 5 Holstein individuals were investigated. The Hanwoo DNA samples included three different colored (5 Black, 5 Yellow and 4 Stripe) animals. Total 126 polymorphisms have been identified and 23 of them are located in the exon region. Also, 5 bp (TTCTC) and 3 bp (TCT) intronic indels in intron 3 and intron 5, respectively, were identified. Out of 23 exonic polymorphisms, 15 SNPs are the missense mutations and the rest of the SNPs are silence mutations. The neighbor-joining phylogenetic tree was constructed for the different colored animals using the obtained KIT gene sequences. Holstein breed showed a clear breed-specific cluster in the phylogenetic tree which is differed from Hanwoo. Also, three colored Hanwoo animals were not discriminated among the breeds. The KIT gene polymorphisms identified in this study will possibly give some solutions for the color variations in cattle with further verifications.


Coat color;KIT gene;Korean cattle;Phylogenetic analysis


Supported by : Rural Development Administration


  1. Olsen, H. G., Vage, D. I., Lien, S. and Klungland, H. 2000. A DNA polymorphism in the bovine c-kit gene. Anim. Genet. 31:68-79.
  2. Olson, T. A. 1999. Genetics of colour variation. In: The Genetics of Cattle (Eds. by R. Fries and A. Ruvinsky). CAB International. Wallingford, UK. pp. 33-53.
  3. Pielberg, G., Olsson, C., Syvanen, A.C. and Andersson, L. 2002. Unexpectedly high allelic diversity at the KIT locus causing dominant white color in the domestic pig. Genetics. 160:305-311.
  4. Reinsch, N., Thomsen, H., Xu, N., Brink, M., Looft, C., Kalm, E., Brockmann, G. A., Grupe, S., Kuhn, C., Schwerin, M., Leyhe, B., Hiendleder, S., Erhardt, G., Medjugorac, I., Russ, I., Forster, M., Reents, R. and Averdunk, G. 1999. A QTL for the degree of spotting in cattle shows synteny with the KIT locus on chromosome 6. J. Hered. 90:629-634.
  5. Spritz, R. A., Giebel, L. B. and Holmes, S. A. 1992. Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. Am. J. Hum. Genet. 50:261-269.
  6. Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M. and Kumar, S. 2011. MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Mol. Biol. Evol. 28:2731-2739.
  7. The Bovine HapMap Consortium. 2009. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds. Science. 324:528-532.
  8. Thompson, J. D., Higgins, D. G., Gibson, T. J. and Clustal, W. 1994. Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positionspecific gap penalties and weight matrix choice. Nucleic Acids Res. 22:4673-4680.
  9. Tian, Q., Frierson, H. F., Krystal, G. W. and Moskaluk, C. A. 1999. Activating c-kit mutations in human germ cell tumors. Am. J. Pathol. 154:1643-1647.
  10. Gari, M., Goodeve, A., Wilson, G., Winship, P., Langabeer, S., Linch, D., Vandenberghe, E., Peak, I., Reilly, J. 1999. C-kit proto-oncogene exon 8 inframe deletion plus insertion mutations in acute myeloid leukaemia. Br. J. Haematol. 105:894-900.
  11. Geissler, E. N., Ryan, M. A. and Housman, D. E. 1988. The dominant white spotting (W) locus of the mouse encodes the c-kit protooncogene. Cell. 55:185-192.
  12. Giuffra, E., Evans, G., Tornsten, A., Wales, R., Day, A., Looft, H., Plastow, G. and Andersson, L. 1999. The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus. Mamm. Genome. 10:1132-1136.
  13. Grosz, M. D. and MacNeil, M. D. 1999. The "'spotted"' locus maps to bovine chromosome 6 in a Hereford-Cross population. J. Hered. 90:233-236.
  14. Haase, B., Brooks, S. A., Schlumbaum, A., Azor, P. J., Bailey, E., Alaeddine, F., Mevissen, M., Burger, D., Poncet, P. A., Rieder, S. and Leeb, T. 2007. Allelic heterogeneity at the equine KIT locus in dominant white (W) horses. PLoS Genetics. 3:e195.
  15. Hayes, B. J., Chamberlain, A. J., Maceachern, S., Savin, K., McPartlan, H., MacLeod, I., Sethuraman, L. and Goddard, M. E. 2009. A genome map of divergent artificial selection between Bostaurus dairy cattle and Bostaurus beef cattle. Anim. Genet. 40:176-184.
  16. Klungland, H., Olsen, H. G., Hassanane, M. S., Mahrous, K. and Vage, D. I. 2000. Coat colour genes in diversity studies. J. Anim. Breed Genet. 117:217-224.
  17. Liu, L., Harris, B., Keehan, M. and Zhang, Y. 2009. Genome scan for the degree of white spotting in dairy cattle. Anim. Genet. 40:975-977.
  18. MacEachern, S., Hayes, B., McEwan, J. and Goddard, M. 2009. An examination of positive selection and changing effective population size in Angus and Holstein cattle populations (Bos taurus) using a high density SNP genotyping platform and the contribution of ancient polymorphism to genomic diversity in domestic cattle. BMC Genomics. 10:181.
  19. Marklund, S., Kijas, J., Rodriguez-Martinez, H., Ronnstrand, L., Funa, K., Moller, M., Lange, D., Edfors-Lilja, I. and Andersson, L. 1998. Molecular basis for the dominant white phenotype in the domestic pig. Genome Res. 8:826-833.
  20. Marklund, S., Moller, M., Sandberg, K. and Andersson, L. 1999. Close association between sequence polymorphism in the KIT gene and the roan coat color in horses. Mamm. Genome. 10:283-288.
  21. Nagata, H., Worobec, A. S., Oh, C. K., Chowdhury, B. A., Tannenbaum, S., Suzuki, Y. and Metcalfe, D. D. 1995. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc. Natl. Acad. Sci. U. S. A. 92: 10560-10564.
  22. Nakata, Y., Kimura, A., Katoh, O., Kawaishi, K., Hyodo, H., Abe, K., Kuramoto, A. and Satow, Y. 1995. C-kit point mutation of extracellular domain in patients with myeloproliferative disorders. Br. J. Haematol. 91:661-663.
  23. Besmer, P., Manova, K., Duttlinger, R., Huang E. J., Packer, A., Gyssler, C. and Bachvarova, R. F. 1993. The kit-ligand (steel factor) and its receptor c-kit/W: pleiotropic roles in gametogenesis and melanogenesis. Dev. Suppl. pp. 125-37.
  24. Brooks, S. A. and Bailey, E. 2005. Exon skipping in the KIT gene causes a Sabino spotting pattern in horses. Mamm. Genome. 16:893-902.
  25. Chabot, B., Stephenson, D. A., Chapman, V. M., Besmer, P. and Bernstein, A. 1988. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 335:88-89.
  26. Fleischman, R. A., Saltman, D. L., Stastny, V. and Zneimer, S. 1991. Deletion of the c-kit protooncogene in the human developmental defect piebald trait. Proc. Natl. Acad. Sci. U. S. A. 88:10885-10889.
  27. Fontanesi, L., Scotti, E. and Russo, V. 2010. Analysis of SNPs in the KIT gene of cattle with different coat colour patterns and perspectives to use these markers for breed traceability and authentication of beef and dairy products. Ital. J. Anim. Sci. 9:e42.
  28. Fontanesi, L., Tazzoli, M., Russo, V. and Beever, J. 2009. Genetic heterogeneity at the bovine KIT gene in cattle breeds carrying different putative alleles at the spotting locus. Anim. Genet. 41:295-303.