title: The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution.
abstract: The complete sequence of the MC1R locus has been assembled, the coding region of the gene is intronless and placed within a 12 kb region flanked by the NULP1 and TUBB4 genes. The immediate promoter region has an E-box site with homology to the M-box consensus known to bind the microphthalmia transcription factor (MITF); however, promoter deletion analysis and transactivation studies have failed to show activation through this element by MITF. Polymorphism within the coding region, immediate 5' promoter region and a variable number tandem repeat (VNTR) minisatellite within the locus have been examined in a collection of Caucasian families and African individuals. Haplotype analysis shows linkage disequilibrium between the VNTR and MC1R coding region red hair variant alleles which can be used to estimate the age of these missense changes. Assuming a mean VNTR mutation rate of 1% and a star phylogeny, we estimate the Arg151Cys variant arose 7500 years before the present day, suggesting these variants may have arisen in the Caucasian population more recently than previously thought.
authors.affiliation: Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Smith
authors.forename: N F
authors.initials: NF
authors.lastname: Box
authors.forename: L H
authors.initials: LH
authors.lastname: Marks
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: D J
authors.initials: DJ
authors.lastname: Smit
authors.forename: J R
authors.initials: JR
authors.lastname: Wyeth
authors.forename: G A
authors.initials: GA
authors.lastname: Huttley
authors.forename: S
authors.initials: S
authors.lastname: Easteal
authors.forename: R A
authors.initials: RA
authors.lastname: Sturm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D019143:Evolution, Molecular; D015870:Gene Expression; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011061:Poly A / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000235:genetics*; D044101:Receptors, Melanocortin; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D011993:Recombinant Fusion Proteins; D011061:Poly A; D004247:DNA; D008156:Luciferases