OMIA:000209-9925 : Coat colour, dominant white in Capra hircus
In other species: dog , domestic cat , ass , horse , pig , llama , cattle , rabbit , domestic yak , alpaca , raccoon dog , Arctic fox
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 172800 (trait) , 164920 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2019
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: Henkel et al. (2019) reported two "CNVs were located in the 3’-flanking region of KIT and associated with a completely white coat color phenotype in Pak Angora goats [this OMIA entry] and a white-spotted coat color phenotype [see OMIA 001737-9925] in Barbari goats, respectively".
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|KIT||v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog||Capra hircus||6||NC_030813.1 (70711232..70793908)||KIT||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1188||Pak Angora, Pakistan (Goat)||White||KIT||KIT^ANG||repeat variation||Naturally occurring variant||ARS1||6||g.70859258_70959918 (3 copies)||This CNV "started ~63 kb downstream of KIT and covered ~100 kb of the genome reference sequence without known coding DNA. The short read-aligments of read-pairs spanning the amplification breakpoints confirmed that the individual copies of the CNV were arranged in tandem in a head to tail orientation" (Henkel et al.,2019)||2019||31841508|
|2019||Henkel, J., Saif, R., Jagannathan, V., Schmocker, C., Zeindler, F., Bangerter, E., Herren, U., Posantzis, D., Bulut, Z., Ammann, P., Drögemüller, C., Flury, C., Leeb, T. :|
|Selection signatures in goats reveal copy number variants underlying breed-defining coat color phenotypes. PLoS Genet 15:e1008536, 2019. Pubmed reference: 31841508 . DOI: 10.1371/journal.pgen.1008536.|
- Created by Frank Nicholas on 09 Apr 2020
- Changed by Frank Nicholas on 17 May 2020