OMIA 000209-9913 : Coat colour, dominant white in Bos taurus

In other species: rabbit , pig , dog , horse , domestic cat , llama , alpaca , Arctic fox , ass , raccoon dog

Possibly relevant human trait(s) and/or gene(s) (MIM number): 172800

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2010

Cross-species summary: The dominant white gene is one of a number of genes that regulate normal growth and proliferation of cells. In fact, it encodes a protein that protrudes through the cell membrane, relaying 'messages' across the membrane, from outside to inside the cell. The transmembrane domain of the protein is a receptor for a growth factor (a protein produced by one type of cell, that acts on another type of cell). The domain inside the cell has tyrosine kinase activity. When a growth factor binds to the receptor on the outside of the cell, this stimulates tyrosine kinase activity inside the cell, which sets off a cascade of phosphorylations, resulting in activation of transcription factors, which in turn activate genes, resulting in multiplication of stem cells, including melanocyte precursor cells, in the developing embryo. This whole process is known as a signal transduction pathway. During embryonic development, the melanosome precursor cells migrate from the neural crest down either side of the body. Under normal circumstances, they eventually meet at the centre of the belly. The cells then proliferate in all directions until they meeting neighbouring cells, thereby filling up all available areas, resulting in a solid mass of melanocytes over the entire body. The dominant white allele produces a defective transmembrane protein which is unable to relay 'messages', resulting in a lack of melanocytes, and hence white coat colour. An interesting aspect of the dominant white gene is that if it is activated at the wrong time, the result can be excess and uncontrolled proliferation of stem cells; in other words, cancer. In fact, at some time in the past, a feline retrovirus (the Hardy-Zuckerman 4 feline sarcoma virus) 'picked up' (by transduction) a copy of the dominant white gene from a cat, and incorporated this gene into its own genome. When this retrovirus infects cats, it activates its own copy of the gene at inappropriate times, causing sarcoma - a malignant tumour of cells derived from connective tissue. Retroviral genes that cause cancer are called oncogenes. The original host version of an oncogene is called a proto-oncogene. Thus, the dominant white gene is actually a proto-oncogene. In this particular case, the oncogene was discovered and named v-kit (where 'v' indicates a viral version of the gene) long before its association with white coat colour was established. The corresponding proto-oncogene is called c-kit, where 'c' stands for cellular. After the discovery and cloning of v-kit in the feline retrovirus by Besmer et al. (1986; Nature 320:415-421), c-kit was identified and mapped first in humans, by Mattei et al. (1987; Cytogenetics and Cell Genetics 46:657 only), and then in mice (Chabot et al., 1988; Nature 335:88-89, 1988), where it was shown to be identical with the long-recognised white-spotting (W) locus. Three years later, Giebel and Spritz (1991; Proceedings of the National Academy of Sciences 88:8696-8699) showed that mutations at the c-kit gene in humans cause piebaldism, which is the human homologue of white spotting (see the MIM entry at the top of this page)

Breed: Hereford.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT KIT proto-oncogene receptor tyrosine kinase Bos taurus 6 NC_037333.1 (70166681..70254049) KIT Homologene, Ensembl, NCBI gene

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2016 Randhawa, I.A., Khatkar, M.S., Thomson, P.C., Raadsma, H.W. :
A Meta-Assembly of Selection Signatures in Cattle. PLoS One 11:e0153013, 2016. Pubmed reference: 27045296. DOI: 10.1371/journal.pone.0153013.
2013 Druet, T., PĂ©rez-Pardal, L., Charlier, C., Gautier, M. :
Identification of large selective sweeps associated with major genes in cattle. Anim Genet 44:758-62, 2013. Pubmed reference: 23859468. DOI: 10.1111/age.12073.
2010 Hayes, B.J., Pryce, J., Chamberlain, A.J., Bowman, P.J., Goddard, M.E. :
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 6:e1001139, 2010. Pubmed reference: 20927186. DOI: 10.1371/journal.pgen.1001139.
2009 Liu, L., Harris, B., Keehan, M., Zhang, Y. :
Genome scan for the degree of white spotting in dairy cattle. Anim Genet 40:975-7, 2009. Pubmed reference: 19531114. DOI: 10.1111/j.1365-2052.2009.01936.x.
2000 Olsen, H.G., Vage, D.I., Lien, S., Klungland, H. :
A DNA polymorphism in the bovine c-kit gene Animal Genetics 31:71, 2000. Pubmed reference: 10690368.
1999 Grosz, M.D., Fahrenkrug, S., Macneil, M.D. :
Comparative positional candidate cloning: KIT as a candidate gene for the Hereford coat colour phenotype Archiv fur Tierzucht-Archives of Animal Breeding 42:160-162, 1999.
Grosz, M.D., Stone, R.T. :
A single nucleotide polymorphism in the bovine kit oncogene (Hardy-Zuckerman 4 feline sarcoma viral (v-kit) oncogene homolog) Animal Genetics 30:394, 1999. Pubmed reference: 10582296.
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., Averdunk, G. :
A QTL for the degree of spotting in cattle shows synteny with the KIT locus on chromosome 6 Journal of Heredity 90:629-634, 1999. Pubmed reference: 10589513.

Edit History


  • Created by Frank Nicholas on 13 Oct 2010
  • Changed by Frank Nicholas on 29 Aug 2011
  • Changed by Frank Nicholas on 09 Dec 2011