OMIA 001199-9627 : Coat colour, extension in Vulpes vulpes
In other species: cattle , dog , horse , pig , sheep , jaguar , jaguarundi , American black bear , woolly mammoth , domestic cat , rabbit , domestic guinea pig , goat , Arctic fox , rock pocket mouse , oldfield mouse , gray squirrel , lesser earless lizard , little striped whiptail , water buffalo , domestic yak , alpaca , , coyote , reindeer , Geoffroy's cat , Colocolo , ass , Arabian camel , Mongolian gerbil , raccoon dog , fallow deer , zebu , lorises , antarctic fur seal
Category: Pigmentation phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: no
Key variant known: yes
Year key variant first reported: 1997
Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; now known as MC1R). This receptor controls the level of tyrosinase within melanocytes. Tyrosinase is the limiting enzyme involved in synthesis of melanins: high levels of tyrosinase result in the production of eumelanin (dark colour, e.g. brown or black), while low levels result in the production of phaeomelanin (light colour, e.g. red or yellow). When melanocyte-stimulating hormone (MSH) binds to its receptor, the level of tyrosinase is increased, leading to production of eumelanin. The wild-type allele at the extension locus corresponds to a functional MSHR, and hence to dark pigmentation in the presence of MSH. As explained by Schneider et al. (PLoS Genet 10(2): e1004892; 2015), "The most common causes of melanism (black coat) mutations are gain-of-function alterations in MC1R, or loss-of function alterations in ASIP, which encodes Agouti signaling protein, a paracrine signaling molecule that inhibits MC1R signaling". Mutations in MC1R have been associated with white colouring in several species.
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on extensive evidence in other mammal species that the Extension (E) locus corresponds to the MC1R gene), Vage et al. (1997) cloned and characterized the fox extension locus, providing strong evidence that the Alaska Silver allele, E(A), which confers dark pigmentation, is due to a C125R amino-acid substitution in the melanocyte-stimulating hormone receptor.
Liu et al. (2016) confirmed the findings by Vage et al. (1997) when they reported that the "c.373T>C in the coding region of the MC1R gene is probably associated with the brown phenotype of chocolate foxes". As Vage et al. (1997) reported protein coordinates for the variant and Liu et al. (2016) reported cDNA coordinates, the variant was initially added twice to OMIA variant tables (OMIA variant IDs 115 and 116). After review of the paper by Vage et al. (1997) and revision of the location on the reference genome the variant information was updated for OMIA variant 115, and OMIA variant 116 was deleted [20/01/2023].
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MC1R||Vulpes vulpes||-||no genomic information (-..-)||MC1R||Ensembl|
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.
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|
|115||Coat colour, extension||MC1R||E^A||missense||Naturally occurring variant||VulVul2.2||NW_020356486.1||g.6101019T>C||c.373T>C||p.(C125R)||XM_026005028.1; XP_025860813.1||1997||9054949|
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.
|2022||Ji, R.L., Tao, Y.X. :|
|Melanocortin-1 receptor mutations and pigmentation: Insights from large animals. Prog Mol Biol Transl Sci 189:179-213, 2022. Pubmed reference: 35595349. DOI: 10.1016/bs.pmbts.2022.03.001.|
|2016||Liu, Z., Gong, Y., Feng, M., Duan, L., Li, Y., Li, X. :|
|Genetic variations of the coding region of the melanocortin receptor 1 (MC1R) gene in the fox. Vet Dermatol 27:135-e36, 2016. Pubmed reference: 27072328. DOI: 10.1111/vde.12303.|
|2013||Nowacka-Woszuk, J., Salamon, S., Gorna, A., Switonski, M. :|
|Missense polymorphisms in the MC1R gene of the dog, red fox, arctic fox and Chinese raccoon dog. J Anim Breed Genet 130:136-41, 2013. Pubmed reference: 23496014. DOI: 10.1111/jbg.12005.|
|Switonski, M., Mankowska, M., Salamon, S. :|
|Family of melanocortin receptor (MCR) genes in mammals-mutations, polymorphisms and phenotypic effects. J Appl Genet 54:461-72, 2013. Pubmed reference: 23996627. DOI: 10.1007/s13353-013-0163-z.|
|1997||Vage, D.I., Lu, D.S., Klungland, H., Lien, S., Adalsteinsson, S., Cone, R.D. :|
|A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes Nature Genetics 15:311-315, 1997. Pubmed reference: 9054949. DOI: 10.1038/ng0397-311.|
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