title: Compelling evidence that a single nucleotide substitution in TYRP1 is responsible for coat-colour polymorphism in a free-living population of Soay sheep.
abstract: Identifying the genes that underlie phenotypic variation in natural populations is a central objective of evolutionary genetics. Here, we report the identification of the gene and causal mutation underlying coat colour variation in a free-living population of Soay sheep (Ovis aries). We targeted tyrosinase-related protein 1 (TYRP1), a positional candidate gene based on previous work that mapped the Coat colour locus to an approximately 15cM window on chromosome 2. We identified a non-synonymous substitution in exon IV that was perfectly associated with coat colour. This polymorphism is predicted to cause the loss of a cysteine residue that is highly evolutionarily conserved and likely to be of functional significance. We eliminated the possibility that this association is due to the presence of strong linkage disequilibrium with an unknown regulatory mutation by demonstrating that there is no difference in relative TYRP1 expression between colour morphs. Analysis of this putative causal mutation in a complex pedigree of more than 500 sheep revealed almost perfect co-segregation with coat colour (chi2-test, p<0.0001, LOD=110.20), and very tight linkage between Coat colour and TYRP1 (LOD=29.50).
authors.affiliation: Department of Animal and Plant Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UK. j.gratten@sheffield.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Gratten
authors.forename: D
authors.initials: D
authors.lastname: Beraldi
authors.forename: B V
authors.initials: BV
authors.lastname: Lowder
authors.forename: A F
authors.initials: AF
authors.lastname: McRae
authors.forename: P M
authors.initials: PM
authors.lastname: Visscher
authors.forename: J M
authors.initials: JM
authors.lastname: Pemberton
authors.forename: J
authors.initials: J
authors.lastname: Slate
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D017931:DNA Primers; D006200:Hair Color / Q000235:genetics*; D015810:Linkage Disequilibrium; D008126:Lod Score; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010858:Pigmentation / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D034561:Sheep, Domestic / Q000235:genetics* / Q000502:physiology
chemical_list: D017931:DNA Primers; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1