OMIA:001249-9615 : Coat colour, brown, TYRP1-related in Canis lupus familiaris
In other species: cattle , horse , domestic cat , sheep , pig , golden hamster , North American deer mouse , goat , American mink , rabbit , Mongolian gerbil , American black bear
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612271 (trait) , 203290 (trait) , 115501 (gene)
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: 2002
Species-specific name: This is the classic B (Brown) locus described by Little (1957)
Species-specific symbol: B locus
Species-specific description: Brancalion et al. (2021): "The Brown (B) locus is controlled by Tyrosinase-related protein 1 (TYRP1. I), located on CFA11 (Schmutz et al. 2002). TYRP1. I encodes an intramelasomal peptide with a key role in the pathway of eumelanin biosynthesis (Kaelin et al. 2012). Consequently, variants in TYRP1 disrupt the production of eumelanin but have no effect on pheomelanin synthesis. Three recessive TYRP1 alleles, termed ‘bs’, ‘bd’ and ‘bc’, are commonly responsible for the dilution of black pigment to brown (Schmutz et al. 2002; ...). The dominant wt allele, ‘B’, favours the production of normal black eumelanin. ... As TYRP1 variants affect the synthesis of eumelanin and not pheomelanin, they have no effect on coat colour in dogs that are homozygous recessive at MC1R (e/e). Further, the variation in coat colour from yellow to red in e/e dogs was not found to be attributed to variants at the Brown locus (Schmutz et al. 2002). A two-gene interaction between the genotype at TYRP1 and MC1R, however, has been found to determine colouration of the nose and paw pads. Normally black, the nose and paw pads of E/e or E/E dogs with two or more recessive Brown alleles were found to be lightened to brown, whereas in e/e dogs, the normally black nose and paw pads were lightened to either brown or ‘self’ coloured. This phenomenon occurs because different genetic pathways control the migration of pigment into the hair shaft and keratinised skin (Schmutz et al. 2002; Schmutz & Berryere 2007)."
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the gene corresponding to the brown locus in mice), Schmutz et al. (2002) were the first to sequence the TYRP1 gene in dogs. They identified three likely causal variants, namely "a premature stop codon in exon 5 (Q331ter) [named allele b^s], . . .a [deletion of a] proline residue in exon 5 (345delP) [named allele b^d] . . . [and] A third variant in exon 2 (S41C) [named allele b^c). . . . All 43 of the brown group carried two or more of these sequence variants likely to interfere with TYRP1 function, whereas 0 of 34 in the black group carried two or more of these variants (10 carried one variant)". The authors concluded that "all three [mutations] affect eumelanin production and alter black pigmentation to brown".
Gerding et al. (2011) showed that the typical "grey" coat colour in Weimaraners is due to homozygosity for a non-functional allele (or heterozygosity for different non-functional alleles) at the TYRP1 locus; and that the "blue" coat colour in the same breed is due to the presence of one or two functional alleles at this locus. Thus, "blue" is dominant to "grey". By studying haplotypes, they were also able to show that the funcational allele is not a "reversion" from within the breed.
Letko and Drögemüller (2017) identified alleles b^c and b^d in Leonberger dogs.
Hrckova Turnova et al. (2017) reported a new allele (c.555T>G; p.Tyr185*) in a single pedigree of Australian Shepherd dogs.
Jancuskova et al. (2018) reported the same c.555T>G allele as being more widespread in the Australian Shepherd breed and "also its close relative Miniature American Shepherd".
Wright et al. (2019) reported a likely causal variant (CFA11:33326719; c.1025T>G; p.Phe342Cys) strongly associated with liver colour in Lancashire Heelers.
Van Buren et al. (2021) reported a 6th variant: "(NM_001194966.1, c.125G>A, p.Cys42Tyr) in exon 1 of the husky and husky‐mixes whose brown phenotype could not be explained by the previously known b‐variants." They named this variant b^h.
Prevalence: Van Buren et al. (2021): "All genotyped brown husky and husky‐mixes carrying the b^h allele were compound heterozygotes with either the bs or bc alleles, consistent with two mutant alleles required for a brown coat. No unrelated huskies had the b^h allele."
Breeds: Australian Shepherd, German Shepherd Dog, Lancashire heeler, Leonberger, Miniature American Shepherd, Siberian Husky.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|TYRP1||tyrosinase-related protein 1||Canis lupus familiaris||11||NC_051815.1 (34222689..34240515)||TYRP1||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|
|31||Brown||TYRP1||b^c||missense||Naturally occurring variant||CanFam3.1||11||g.33317810T>A||c.121T>A||p.(C41S)||rs851939320||rs851939320||2002||12140685||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. Correction to genomic details provided by professor Claire Wade August 2018. Correction to g and c. details provided by Professor Tosso Leeb 11 Feb 2020.|
|1282||Siberian Husky||Brown||TYRP1||b^h||missense||Naturally occurring variant||CanFam3.1||11||g.33317814G>A||c.125G>A||p.(C42Y)||NM_001194966.1, c.125G>A, p.Cys42Tyr (Van Buren et al., 2021)||2021||33421162|
|797||Australian Shepherd||Brown||TYRP1||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||11||g.33319349T>G||c.555T>G||p.(Y185*)||ROS_Cfam_1.0 g.34224397T>G ENSCAFT00845015439.1:c.555T>G ENSCAFP00845011991.1:p.Tyr185Ter||rs1152388483||rs1152388483||2017||28497851|
|267||Brown||TYRP1||b^s||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||11||g.33326685C>T||c.991C>T||p.(Gln331*)||rs850566878||rs850566878||2002||12140685||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
|1113||Lancashire heeler||Liver||TYRP1||b^e||missense||Naturally occurring variant||CanFam3.1||11||g.33326719T>G||c.1025T>G||p.(F342C)||2019||31468558|
|796||Brown||TYRP1||b^d||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||11||g.33326727_33326729del||c.1033_1035del||p.(P345del)||rs851422848||rs851422848||2002||12140685|
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.
|2023||Arizmendi, A., Rudd Garces, G., Crespi, J.A., Olivera, L.H., Barrientos, L.S., Peral García, P., Giovambattista, G. :|
|Analysis of Doberman Pinscher and Toy Poodle samples with targeted next-generation sequencing. Gene 853:147069, 2023. Pubmed reference: 36427679 . DOI: 10.1016/j.gene.2022.147069.|
|2022||[No authors listed] :|
|Canine coat pigmentation genetics: a review. Anim Genet 53:474-475, 2022. Pubmed reference: 35510419 . DOI: 10.1111/age.13185.|
|Brancalion, L., Haase, B., Wade, C.M. :|
|Canine coat pigmentation genetics: a review. Anim Genet 53:33-34, 2022. Pubmed reference: 34751460 . DOI: 10.1111/age.13154.|
|2021||Van Buren, S.L., Mickelson, J.R., Minor, K.M. :|
|A novel TYRP1 mutation associated with brown coat color in Siberian huskies. Anim Genet 52:245-246, 2021. Pubmed reference: 33421162 . DOI: 10.1111/age.13037.|
|2019||Dreger, D.L., Hooser, B.N., Hughes, A.M., Ganesan, B., Donner, J., Anderson, H., Holtvoigt, L., Ekenstedt, K.J. :|
|True Colors: Commercially-acquired morphological genotypes reveal hidden allele variation among dog breeds, informing both trait ancestry and breed potential. PLoS One 14:e0223995, 2019. Pubmed reference: 31658272 . DOI: 10.1371/journal.pone.0223995.|
|van Rooy, D., Wade, C.M. :|
|Association between coat colour and the behaviour of Australian Labrador retrievers. Canine Genet Epidemiol 6:10, 2019. Pubmed reference: 31798910 . DOI: 10.1186/s40575-019-0078-z.|
|Wright, H.E., Schofield, E., Mellersh, C.S., Burmeister, L.M. :|
|A novel TYRP1 variant is associated with liver and tan coat colour in Lancashire Heelers. Anim Genet 50:783, 2019. Pubmed reference: 31468558 . DOI: 10.1111/age.12839.|
|2018||Jancuskova, T., Langevin, M., Pekova, S. :|
|TYRP1:c.555T>G is a recurrent mutation found in Australian Shepherd and Miniature American Shepherd dogs. Anim Genet 49:500-501, 2018. Pubmed reference: 30109695 . DOI: 10.1111/age.12709.|
|2017||Hrckova Turnova, E., Majchrakova, Z., Bielikova, M., Soltys, K., Turna, J., Dudas, A. :|
|A novel mutation in the TYRP1 gene associated with brown coat colour in the Australian Shepherd Dog Breed. Anim Genet 48:626, 2017. Pubmed reference: 28497851 . DOI: 10.1111/age.12563.|
|Letko, A., Drögemüller, C. :|
|Two brown coat colour-associated TYRP1 variants (b(c) and b(d) ) occur in Leonberger dogs. Anim Genet 48:732-733, 2017. Pubmed reference: 28983931 . DOI: 10.1111/age.12612.|
|2015||Monteagudo, L.V., Tejedor, M.T. :|
|The b(c) allele of TYRP1 is causative for the recessive brown (liver) colour in German Shepherd dogs. Anim Genet 46:588-9, 2015. Pubmed reference: 26370740 . DOI: 10.1111/age.12337.|
|2012||Kaelin, C., Barsh, G.S. :|
|Molecular genetics of coat colour, texture and length in the dog. . Genetics of the Dog: 2nd Edition :57-82, 2012.|
|Schmutz, S.M., Melekhovets, Y. :|
|Coat color DNA testing in dogs: theory meets practice. Mol Cell Probes 26:238-42, 2012. Pubmed reference: 22507852 . DOI: 10.1016/j.mcp.2012.03.009.|
|2011||Gerding, WM., Schreiber, S., Dekomien, G., Epplen, JT. :|
|Tracing the origin of 'blue Weimaraner' dogs by molecular genetics. J Anim Breed Genet 128:153-60, 2011. Pubmed reference: 21385230 . DOI: 10.1111/j.1439-0388.2010.00888.x.|
|2007||Schmutz, SM., Berryere, TG. :|
|Genes affecting coat colour and pattern in domestic dogs: a review. Anim Genet 38:539-49, 2007. Pubmed reference: 18052939 . DOI: 10.1111/j.1365-2052.2007.01664.x.|
|2005||Cargill, E.J., Famula, T.R., Schnabel, R.D., Strain, G.M., Murphy, K.E. :|
|The color of a Dalmatian's spots: linkage evidence to support the TYRP1 gene. BMC Vet Res 1:1, 2005. Pubmed reference: 16045797 . DOI: 10.1186/1746-6148-1-1.|
|2002||Schmutz, S.M., Berryere, T.G., Goldfinch, A.D. :|
|TYRP1 and MC1R genotypes and their effects on coat color in dogs Mammalian Genome 13:380-387, 2002. Pubmed reference: 12140685 . DOI: 10.1007/s00335-001-2147-2.|
|1957||Little, C.C. :|
|The Inheritance of Coat Color in Dogs Comstock Publishing Associates, Cornell University Press, Ithaca, NY :, 1957.|
- Created by Frank Nicholas on 04 Jun 2011
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