OMIA:001249-9940 : Coat colour, brown, TYRP1-related in Ovis aries (sheep)
In other species: Rhesus monkey , dog , American black bear , domestic cat , horse , pig , taurine cattle , goat , rabbit , golden hamster , North American deer mouse , Mongolian gerbil , American mink
Categories: 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: 2007
Inheritance: The dark vs light coat colour segregation in Soay sheep is consistent with single-locus inheritance in which dark is dominant to light (Doney et al., 1974; Ryder et al., 1974; Coltman and Pemberton, 2004)
Mapping: In Soay sheep, Beraldi et al. (2006) mapped this locus to a small region of OAR2 very near microsatellite BMS678. Comparative mapping implicated the well-known TRYP1 (brown) coat-colour locus, in which a causative mutation was subsequently found (see below).
In a QTL resource flock derived from an Awassi x Merino x Merino backcross, Raadsma et al. (2013) conducted a genome scan for 13 skin and fibre pigmentation traits, using 189 microsatellites on 177 backcross wethers, the F1 sire and both grandparents. Of the 19 highly-significant QTL detected, 13 mapped to a region of chromosome OAR2 that includes the TYRP1 gene, and 5 mapped to a single region of chromosome OAR19 that includes another coat-colour gene, namely MITF.
By conducting a GWAS on 51 brown and 38 black sheep of the Valais Red breed that is characterised by its brown coat, Paris et al. (2019) mapped the brown/black polymorphism in this breed to the TYRP1 gene on chromosome OVA2.
Markers: Having identified the TYRP1 gene as a strong positional candidiate, subsequent sequencing and association analysis enabled Raadsma et al. (2013) to show that 10%-46% of variation in 13 pigmentation traits is due to a non-synonymous SNP (c.2240C>G) in exon 2 of TYRP1. Up to 83% of variation was accounted for when the model also included the MITF-containing QTL on chromosome OAR19.
Molecular basis: Details of the Soay mutation were reported by Gratten et al. (2007): "a G→T transversion at nucleotide position 869 in exon IV (hereafter TYRP1 869G→T) was perfectly associated with coat colour; light sheep (n=6) were homozygous for T at this position, whereas dark sheep (n=6) were either homozygous for G or heterozygous (Fisher's exact test, p=0.002). . . . The TYRP1 869G→T mutation is predicted to cause the replacement of a cysteine (Cys) residue with phenylalanine at codon 290 (C290F). An amino acid alignment revealed that the Cys residue is conserved across all available vertebrates, suggesting that nucleotide position 869 may be under strong functional constraint and that dark coat colour is ancestral to light".
Interestingly, the above mutation was not present in the Awassi x Merino x Merino resource flock reported by Raadsma et al. (2013), and in which a new likely causal variant (c.2240C>G; p.A???V) was reported.
By analysing sequence data in and around the TYRP1 locus, obtained from whole-genome-sequencing of two brown and one black Valais Red sheep, Paris et al. (2019) identified two new brown alleles, namely a "frame‐shift variant TYRP1:c.86_87delGA [designated] as b^VS1 and the nonsense variant TYRP1:c.1066C>T [desiganted] as b^VS2".
Have human generated variants been created, e.g. through genetic engineering and gene editing
Prevalence: Paris et al. (2019) reported that "the b^VS 1 allele occurs only in local breeds of Switzerland whereas the b^VS 2 allele seems to be more widespread across Europe."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|TYRP1||tyrosinase-related protein 1||Ovis aries||2||NC_056055.1 (81182552..81200943)||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|
|227||Brown||TYRP1||missense||Naturally occurring variant||Oar_rambouillet_v1.0||2||c.2240C>G||p.(A???V)||2013||23451726|
|1127||Valais Red (Sheep)||Brown||TYRP1||b^VS1||deletion, small (<=20)||Naturally occurring variant||Oar_rambouillet_v1.0||2||g.87540706_87540707del||c.86_87del||p.(E29Vfs*5)||NM_001130023.1: c.86_87delGA; NP_001123495.1: p.(Glu29ValfsTer5)||2019||31571241||210906 to conform to HGVS notation, FN removed GA from g.87540706_87540707delGA and c.86_87delGA|
|226||Soay (Sheep)||Tawny (light brown)||TYRP1||b^Soay||missense||Naturally occurring variant||Oar_rambouillet_v1.0||2||g.87545636G>T||c.869G>T||p.(C290F)||rs402624085||2007||17254985||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.|
|1128||Valais Red (Sheep)||Brown||TYRP1||b^VS2||nonsense (stop-gain)||Naturally occurring variant||Oar_rambouillet_v1.0||2||g.87549195C>T||c.1066C>T||p.(R356*)||NM_001130023.1: c.1066C>T; NP_001123495.1: p.(Arg356*)||rs1085637427||2019||31571241|
Cite this entry
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||Paris, J.M., Letko, A., Häfliger, I.M., Ammann, P., Flury, C., Drögemüller, C. :|
|Identification of two TYRP1 loss-of-function alleles in Valais Red sheep. Anim Genet , 2019. Pubmed reference: 31571241. DOI: 10.1111/age.12863.|
|2013||Feulner, P.G., Gratten, J., Kijas, J.W., Visscher, P.M., Pemberton, J.M., Slate, J. :|
|Introgression and the fate of domesticated genes in a wild mammal population. Mol Ecol , 2013. Pubmed reference: 23786437. DOI: 10.1111/mec.12378.|
|Raadsma, H.W., Jonas, E., Fleet, M.R., Fullard, K., Gongora, J., Cavanagh, C.R., Tammen, I., Thomson, P.C. :|
|QTL and association analysis for skin and fibre pigmentation in sheep provides evidence of a major causative mutation and epistatic effects. Anim Genet 44:547-59, 2013. Pubmed reference: 23451726. DOI: 10.1111/age.12033.|
|2012||Gratten, J., Pilkington, J.G., Brown, E.A., Clutton-Brock, T.H., Pemberton, J.M., Slate, J. :|
|Selection and microevolution of coat pattern are cryptic in a wild population of sheep. Mol Ecol 21:2977-90, 2012. Pubmed reference: 22432567. DOI: 10.1111/j.1365-294X.2012.05536.x.|
|2010||Gratten, J., Wilson, AJ., McRae, AF., Beraldi, D., Visscher, PM., Pemberton, JM., Slate, J. :|
|No evidence for warming climate theory of coat colour change in Soay sheep: a comment on Maloney et al. Biol Lett 6:678-9; discussion 680-1, 2010. Pubmed reference: 20375045. DOI: 10.1098/rsbl.2010.0160.|
|Maloney, S.K., Fuller, A., Mitchell, D. :|
|A warming climate remains a plausible hypothesis for the decrease in dark Soay sheep Biology Letters 6:680-681, 2010. DOI: 10.1098/rsbl.2009.0424.|
|2009||Maloney, SK., Fuller, A., Mitchell, D. :|
|Climate change: is the dark Soay sheep endangered? Biol Lett 5:826-9, 2009. Pubmed reference: 19625302. DOI: 10.1098/rsbl.2009.0424.|
|2008||Gratten, J., Wilson, AJ., McRae, AF., Beraldi, D., Visscher, PM., Pemberton, JM., Slate, J. :|
|A localized negative genetic correlation constrains microevolution of coat color in wild sheep. Science 319:318-20, 2008. Pubmed reference: 18202287. DOI: 10.1126/science.1151182.|
|2007||Gratten, J., Beraldi, D., Lowder, BV., McRae, AF., Visscher, PM., Pemberton, JM., Slate, J. :|
|Compelling evidence that a single nucleotide substitution in TYRP1 is responsible for coat-colour polymorphism in a free-living population of Soay sheep. Proc Biol Sci 274:619-26, 2007. Pubmed reference: 17254985. DOI: 10.1098/rspb.2006.3762.|
|2006||Beraldi, D., McRae, AF., Gratten, J., Slate, J., Visscher, PM., Pemberton, JM. :|
|Development of a linkage map and mapping of phenotypic polymorphisms in a free-living population of Soay sheep (Ovis aries). Genetics 173:1521-37, 2006. Pubmed reference: 16868121. DOI: 10.1534/genetics.106.057141.|
- Created by Frank Nicholas on 23 Oct 2007
- Changed by Frank Nicholas on 08 Oct 2011
- Changed by Frank Nicholas on 09 Dec 2011
- Changed by Frank Nicholas on 25 Apr 2013
- Changed by Frank Nicholas on 04 Oct 2019