OMIA 000209-30538 : Coat colour, dominant white in Vicugna pacos

In other species: rabbit , pig , cattle , dog , horse , domestic cat , llama , Arctic fox , ass , 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: 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)

Inheritance: Valbonesi et al. (2011) provided evidence of autosomal dominant inheritance.

Jones et al. (2019) concluded that their "data also support the hypothesis that the grey phenotype is autosomal dominant and that the mutation is most likely homozygous lethal."

Markers: Jackling et al. (2012) provided evidence for "a strong association but not unequivocal relationship between the BEW phenotype and KIT genotype".

Molecular basis: Jones et al. (2019) reported that their "results confirm that the classic grey phenotype in alpacas is the result of a c.376G>A (p.Gly126Arg) SNP in exon 3 of KIT."

Clinical features: There is some evidence that the blue-eyed white (BEW) phenotype in alpacas is a variant of this locus (Jackling et al., 2012).

Prevalence: Jones et al. (2019) reported that "an additional 488 alpacas were genotyped for this [c.376G>A; (p.Gly126Arg)] SNP using the tetra-primer amplification refractory mutation system PCR (Tetra-primer ARMS-PCR). All classic grey alpacas were observed to be heterozygous, and 99.3% of non-grey dark base colour alpacas were found to be homozygous for the wildtype allele [c.376G; p.126Gly] in this position."

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

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
Classic grey coat colour KIT missense c.376G>A p.(Gly126Arg) 2019 31297861

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.
2019 Jones, M., Sergeant, C., Richardson, M., Groth, D., Brooks, S., Munyard, K., Jones, M., Sergeant, C., Richardson, M., Groth, D., Brooks, S., Munyard, K. :
A non-synonymous SNP in exon 3 of the KIT gene is responsible for the classic grey phenotype in alpacas (Vicugna pacos). Anim Genet 50:493-500, 2019. Pubmed reference: 31297861. DOI: 10.1111/age.12814.
2012 Jackling, F.C., Johnson, W.E., Appleton, B.R. :
The Genetic Inheritance of the Blue-eyed White Phenotype in Alpacas (Vicugna pacos). J Hered :, 2012. Pubmed reference: 23144493. DOI: 10.1093/jhered/ess093.
2011 Valbonesi, A., Apaza, N., La Manna, V., Gonzales, M.L., Huanca, T., Renieri, C. :
Inheritance of white, black and brown coat colours in alpaca (Vicuna pacos) Small Ruminant Research 99:16–19 , 2011.
2005 Gauly, M., Vaughan, J., Hogreve, SK., Erhardt, G. :
Brainstem auditory-evoked potential assessment of auditory function and congenital deafness in llamas (Lama glama) and alpacas (L. pacos). J Vet Intern Med 19:756-60, 2005. Pubmed reference: 16231723.

Edit History


  • Created by Frank Nicholas on 12 Nov 2010
  • Changed by Frank Nicholas on 23 Nov 2012
  • Changed by Frank Nicholas on 13 Sep 2019