OMIA 001249-9940 : Coat colour, brown in Ovis aries

In other species: cattle , horse , dog , domestic cat , pig , golden hamster , North American deer mouse , goat , American mink , rabbit

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 612271 , 203290

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.

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, this mutation was not present in the Awassi x Merino x Merino resource flock reported by Raadsma et al. (2013).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TYRP1 tyrosinase-related protein 1 Ovis aries 2 NC_019459.2 (80644559..80661477) TYRP1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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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
Coat colour, brown TYRP1 missense c.2240C>G p.A???V 2013 23451726
Coat colour, brown TYRP1 missense Oar_v3.1 2 g.80608128G>T c. 869G>T p.C290F 2008 18202287 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
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.

Edit History


  • 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