Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
17254985
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).
DATE PUBLISHED
2007 Mar 7
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2007/01/27 09:00
medline 2007/03/16 09:00
entrez 2007/01/27 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Gratten J Gratten J J Department of Animal and Plant Sciences, University of Sheffield, Western Bank, Sheffield S10 2TN, UK. j.gratten@sheffield.ac.uk
Beraldi D Beraldi D D
Lowder BV Lowder B V BV
McRae AF McRae A F AF
Visscher PM Visscher P M PM
Pemberton JM Pemberton J M JM
Slate J Slate J J
INVESTIGATORS
JOURNAL
VOLUME: 274
ISSUE: 1610
TITLE: Proceedings. Biological sciences / The Royal Society
ISOABBREVIATION: Proc. Biol. Sci.
YEAR: 2007
MONTH: Mar
DAY: 7
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0962-8452
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Proc Biol Sci
COUNTRY: England
ISSNLINKING: 0962-8452
NLMUNIQUEID: 101245157
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Anim Genet. 2003 Jun;34(3):169-75 12755816
Cites Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5268-73 12704245
Cites Science. 2004 Mar 19;303(5665):1870-3 15031505
Cites Mol Ecol. 2004 Sep;13(9):2505-22 15315666
Cites Evolution. 2004 Aug;58(8):1794-808 15446431
Cites Mol Ecol. 2004 Nov;13(11):3261-73 15487987
Cites Proc Natl Acad Sci U S A. 1988 Jun;85(12):4392-6 3132713
Cites Proc Natl Acad Sci U S A. 1990 Sep;87(18):7010-4 2119500
Cites Genetics. 1990 Oct;126(2):443-9 2245916
Cites Nucleic Acids Res. 1990 Dec 25;18(24):7293-8 2124349
Cites Pigment Cell Res. 1990 Oct;3(4):177-80 1963944
Cites Am J Hum Genet. 1996 Jun;58(6):1145-56 8651291
Cites Philos Trans R Soc Lond B Biol Sci. 1997 Jul 29;352(1355):839-50 9279899
Cites Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 9396791
Cites Am J Hum Genet. 1998 Jul;63(1):259-66 9634505
Cites J Biol Chem. 1998 Nov 27;273(48):31801-5 9822646
Cites Mamm Genome. 1999 Jan;10(1):39-43 9892731
Cites Hum Mutat. 1999;13(2):99-115 10094567
Cites Mol Ecol. 2005 Feb;14(2):363-79 15660931
Cites J Hered. 2005 Jul-Aug;96(4):289-301 15858157
Cites Proc Biol Sci. 2005 Aug 22;272(1573):1633-40 16087416
Cites Genetics. 2005 Sep;171(1):251-8 15965254
Cites Mol Ecol. 2005 Oct;14(12):3623-42 16202085
Cites Am Nat. 2006 Jan;167(1):1-15 16475095
Cites PLoS Genet. 2006 Feb;2(2):e13 16462944
Cites Trends Genet. 2006 Jun;22(6):301-5 16690157
Cites Science. 2006 Jul 7;313(5783):101-4 16825572
Cites Genetics. 2006 Jul;173(3):1521-37 16868121
Cites Heredity (Edinb). 2006 Sep;97(3):222-34 16823403
Cites Curr Biol. 2001 Apr 17;11(8):550-7 11369199
Cites Science. 2001 May 25;292(5521):1528-31 11375487
Cites Annu Rev Genet. 2001;35:303-39 11700286
Cites Evolution. 2001 Oct;55(10):2116-25 11761070
Cites Pigment Cell Res. 2001 Dec;14(6):437-44 11775055
Cites Genetics. 2002 Apr;160(4):1587-97 11973312
Cites Pigment Cell Res. 2002 Jun;15(3):162-73 12028580
Cites Genetics. 2003 Jan;163(1):453-6 12586730
Cites Mol Ecol. 2003 May;12(5):1185-94 12694282
Cites Pigment Cell Res. 2003 Aug;16(4):333-44 12859616
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Amino Acid Sequence
Animals
Base Sequence
Chromosome Mapping
DNA Primers
Hair Color genetics
Linkage Disequilibrium genetics
Lod Score genetics
Molecular Sequence Data genetics
Oxidoreductases metabolism
Pedigree metabolism
Pigmentation physiology
Polymorphism, Single Nucleotide physiology
Sequence Analysis, DNA physiology
Sheep, Domestic physiology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 DNA Primers
EC 1.- Oxidoreductases
EC 1.14.18.- tyrosinase-related protein-1
OTHER ID's
OTHERID SOURCE
PMC2197217 NLM