OMIA 000209-9793 : Coat colour, dominant white in Equus asinus

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

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

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2015

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)

Molecular basis: Haase et al. (2015): a missense variant in exon 4 (c.662A>C; p.Tyr221Ser)

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Equus asinus - no genomic information (-..-) KIT Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Coat colour, dominant white KIT missense c.662A>C p.Y221S 2015 25818843

Reference


2015 Haase, B., Rieder, S., Leeb, T. :
Two variants in the KIT gene as candidate causative mutations for a dominant white and a white spotting phenotype in the donkey. Anim Genet :, 2015. Pubmed reference: 25818843. DOI: 10.1111/age.12282.

Edit History


  • Created by Frank Nicholas on 16 Apr 2015
  • Changed by Frank Nicholas on 16 Apr 2015