The human melanocortin-1 receptor locus: Analysis of transcription unit, locus polymorphism and haplotype evolution

Aaron G. Smith; Neil F. Box; Lisa H. Marks; Wei Chen; Darren J. Smit; Jason R. Wyeth; Gavin A. Huttley; Simon Easteal; Richard A. Sturm

doi:10.1016/S0378-1119(01)00791-0

The human melanocortin-1 receptor locus: Analysis of transcription unit, locus polymorphism and haplotype evolution

Aaron G. Smith, Neil F. Box, Lisa H. Marks, Wei Chen, Darren J. Smit, Jason R. Wyeth, Gavin A. Huttley, Simon Easteal, Richard A. Sturm^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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.

Original language	English
Pages (from-to)	81-94
Number of pages	14
Journal	Gene
Volume	281
Issue number	1-2
DOIs	https://doi.org/10.1016/S0378-1119(01)00791-0
Publication status	Published - 27 Dec 2001

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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.",

keywords = "MC1R, Melanin, Melanocyte, Pigmentation, Red hair, Skin color",

author = "Smith, {Aaron G.} and Box, {Neil F.} and Marks, {Lisa H.} and Wei Chen and Smit, {Darren J.} and Wyeth, {Jason R.} and Huttley, {Gavin A.} and Simon Easteal and Sturm, {Richard A.}",

year = "2001",

month = dec,

day = "27",

doi = "10.1016/S0378-1119(01)00791-0",

language = "English",

volume = "281",

pages = "81--94",

journal = "Gene",

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T1 - The human melanocortin-1 receptor locus

T2 - Analysis of transcription unit, locus polymorphism and haplotype evolution

AU - Smith, Aaron G.

AU - Box, Neil F.

AU - Marks, Lisa H.

AU - Chen, Wei

AU - Smit, Darren J.

AU - Wyeth, Jason R.

AU - Huttley, Gavin A.

AU - Easteal, Simon

AU - Sturm, Richard A.

PY - 2001/12/27

Y1 - 2001/12/27

N2 - 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.

AB - 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.

KW - MC1R

KW - Melanin

KW - Melanocyte

KW - Pigmentation

KW - Red hair

KW - Skin color

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U2 - 10.1016/S0378-1119(01)00791-0

DO - 10.1016/S0378-1119(01)00791-0

M3 - Article

SN - 0378-1119

VL - 281

SP - 81

EP - 94

JO - Gene

JF - Gene

IS - 1-2

ER -

The human melanocortin-1 receptor locus: Analysis of transcription unit, locus polymorphism and haplotype evolution

Abstract

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