OMIA 001199-494514 : Coat colour, extension in Vulpes lagopus
In other species: cattle , dog , horse , red fox , pig , sheep , jaguar , jaguarundi , American black bear , woolly mammoth , domestic cat , rabbit , domestic guinea pig , goat , 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 recessive
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2005
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.
Inheritance: As summarised by Yan et al. (2013), "According to their coat colour phenotype in winter, arctic fox (Alopex lagopus) are divided naturally into two colour morphs: the white and blue, named polar fox and blue fox respectively . . . . The two coat colours are determined by different alleles at the E locus, where the ‘blue’ allele Ed is dominant over the ‘white’ one E (Adalsteinsson et al. 1987)."
Mapping: Tietgen et al. (2021): "Using a whole-genome approach, we identified the MC1R gene as the sole causal gene underlying Arctic fox Vulpes lagopus fur colour."
Molecular basis: The blue (Ed) allele is a haplotype comprising two missense variants (p.Gly5Cys and p.Phe280Cys) (Våge et al., 2005)
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MC1R||Vulpes lagopus||-||no genomic information (-..-)||MC1R||Ensembl|
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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|
|262||Blue coat colour||MC1R||Ed||missense||Naturally occurring variant||p.[(G5C);(F280C)]||The blue (Ed) allele is a haplotype comprising two missense variants (p.Gly5Cys and p.Phe280Cys) (Våge et al., 2005)||2005||15982782|
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.|
|2021||Tietgen, L., Hagen, I.J., Kleven, O., Bernardi, C.D., Kvalnes, T., Norén, K., Hasselgren, M., Wallén, J.F., Angerbjörn, A., Landa, A., Eide, N.E., Flagstad, Ø., Jensen, H. :|
|Fur colour in the Arctic fox: genetic architecture and consequences for fitness. Proc Biol Sci 288:20211452, 2021. Pubmed reference: 34583587. DOI: 10.1098/rspb.2021.1452.|
|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.|
|2005||Vage, DI., Fuglei, E., Snipstad, K., Beheim, J., Landsem, VM., Klungland, H. :|
|Two cysteine substitutions in the MC1R generate the blue variant of the Arctic fox (Alopex lagopus) and prevent expression of the white winter coat. Peptides 26:1814-7, 2005. Pubmed reference: 15982782. DOI: 10.1016/j.peptides.2004.11.040.|
|1987||Adalsteinsson, S., Hersteinsson, P., Gunnarsson, E. :|
|Fox colors in relation to colors in mice and sheep Journal of Heredity 78:235-237, 1987. Pubmed reference: 3624844.|
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