Post by djoser-xyyman on Dec 6, 2011 20:21:09 GMT -5
Phenotypic Expression of Melanocortin-1 Receptor Mutations in
Black Jamaicans
Colin A. McKenzie, Rosalind M. Harding,n Jennifer BrownTomlinson,w Amanda J. Ray,z KazumasaWakamatsu,y
and Jonathan L. Reesz
Tropical Metabolism Research Unit, University of theWest Indies, Kingston, Jamaica; nInstitute of Biological Anthropology, Oxford University,
Oxford, UK; wDepartment of Dermatology, Kingston Public Hospital, Kingston, Jamaica; zUniversity of Newcastle, Newcastle-upon-Tyne, UK;
yDepartment of Chemistry, Fujita Health University School of Health Sciences,Toyoake, Japan; zDepartment of Dermatology, University of
Edinburgh, Edinburgh, UK
The melanocortin-1 receptor (MC1R) gene is the only
gene identi¢ed that explains substantial variation in
hair color (i.e., that within the normal population). In
northern European populations the majority of redhaired
persons are homozygous for a limited number
of mutations that diminish signaling through the G coupled protein
receptor encoded by the MC1R gene (Valverde et al, 1995). A
clear heterozygote e¡ect is seen on freckling, sun sensitivity, and
risk of skin cancer (Healy et al, 2000; Palmer et al, 2000), and a minority
of individuals with red hair are heterozygotes rather than
homozygotes (or compound heterozygotes) for MC1R mutations
(Flanagan et al, 2000). Although there has been interest in studying
the evolution of the MC1R, and populations from Africa and Asia
have been sampled as part of such work, study of the genotype/
phenotype relationship has been limited to European-derived populations.
We recently had the opportunity to study persons with
red hair but who self-identify themselves as black.
In Jamaica there are persons who self-identify themselves as
black who have auburn/reddish hair, freckles, and a ‘‘rust-colored’’
complexion (sometimes called ‘‘red Ibos’’). As part of an investigation
of the phenotypic expression of MC1R variants in a black
population we have examined MC1R sequence and hair melanins
in four Jamaican ‘‘redheads’’. This study was approved by the University
of theWest Indies/University Hospital of theWest Indies
Ethics Committee.
Samples were obtained from four redheads (ages 3, 11, 30, and
32 y; two boys and two women, respectively) and also from the
mothers of the two boys. DNA extraction from whole blood, sequencing,
and analysis of hair melanins were all carried out using
previously described methods (Sambrook et al, 1989; Ito and
Wakamatsu, 1994; Wakamatsu et al, 2002). Hair melanins were
analyzed in three of the redheads and are expressed as the logarithm
to the base 10 of the concentrations (ng per mg of hair sample)
of eumelanin and pheomelanin.
Sequencing of MC1R revealed that all of the redheads were
compound heterozygotes for variants that are either known, or
predicted to disrupt MC1R function. MC1R genotypes were as
follows (variant positions compared with human consensus sequence:
GenBank accession no. X65634): subject 1, Gly89Arg/
Arg151Cys (his mother is heterozygous for the Arg151Cys variant);
subject 2, 23 STOP/Arg160Trp (his mother is heterozygous
for the 23 STOP variant); subject 3, Asp294His/frameshift at codon
195; subject 4, 23 STOP/Arg151Cys. Hair melanins for subjects
1, 2, and 3 were as follows: log eumelanin 8.3, 8.3, 7.6; log
pheomelanin 4.2, 6.6, 6.5. All of these values are within the range
seen in a white UK sample of MC1R homozygotes selected on
the basis of the red hair phenotype: average log eumelanin 7.570.6;
average log pheomelanin 6.070.9 (Rees et al, unpublished data).
This is one of the ¢rst studies that has examined MC1R variants
and redheaded phenotypes in individuals from a black population
(i.e., with West African ancestry) and, although small,
we think it is of potential interest. The phenotype, which is anecdotally
uncommon (but from our observations cannot be rare), is
striking; it is very easy to distinguish these individuals from black
persons of lighter or darker complexion because there is a reddish-
orange/rust-colored hue to the skin.
There are a number of conclusions we can draw. First, red hair
in this group, as well as in Caucasians, can be accounted for in
terms of mutation of the MC1R: the changes at codons 151, 160,
and 294 are well known (Harding et al, 2000; Schi˛th et al, 1999),
and we have seen the codon 23 stop (as a heterozygous change
only) in another African without red hair. These data suggest the
possibility of a substantial sampling of Caucasian diversity at
MC1R among Jamaican redheads, augmented from an unknown
(possiblyAfrican) source for the 23 stop variant. Second, the melanin
values are within the range seen in white UK individuals of
equivalent MC1R status. This suggests that even on a di¡erent
genetic background MC1R variants exert a signi¢cant phenotypic
e¡ect. Thus, although we assume that there is admixture at
loci other than MC1R, the high penetrance observed is relevant
to studies seeking to explain the evolution of world-wide variation
in skin and hair color. Further studies in Jamaica and in other
African-descent populations are required; particularly with respect
to the presence of a heterozygote e¡ect and sun sensitivity
Black Jamaicans
Colin A. McKenzie, Rosalind M. Harding,n Jennifer BrownTomlinson,w Amanda J. Ray,z KazumasaWakamatsu,y
and Jonathan L. Reesz
Tropical Metabolism Research Unit, University of theWest Indies, Kingston, Jamaica; nInstitute of Biological Anthropology, Oxford University,
Oxford, UK; wDepartment of Dermatology, Kingston Public Hospital, Kingston, Jamaica; zUniversity of Newcastle, Newcastle-upon-Tyne, UK;
yDepartment of Chemistry, Fujita Health University School of Health Sciences,Toyoake, Japan; zDepartment of Dermatology, University of
Edinburgh, Edinburgh, UK
The melanocortin-1 receptor (MC1R) gene is the only
gene identi¢ed that explains substantial variation in
hair color (i.e., that within the normal population). In
northern European populations the majority of redhaired
persons are homozygous for a limited number
of mutations that diminish signaling through the G coupled protein
receptor encoded by the MC1R gene (Valverde et al, 1995). A
clear heterozygote e¡ect is seen on freckling, sun sensitivity, and
risk of skin cancer (Healy et al, 2000; Palmer et al, 2000), and a minority
of individuals with red hair are heterozygotes rather than
homozygotes (or compound heterozygotes) for MC1R mutations
(Flanagan et al, 2000). Although there has been interest in studying
the evolution of the MC1R, and populations from Africa and Asia
have been sampled as part of such work, study of the genotype/
phenotype relationship has been limited to European-derived populations.
We recently had the opportunity to study persons with
red hair but who self-identify themselves as black.
In Jamaica there are persons who self-identify themselves as
black who have auburn/reddish hair, freckles, and a ‘‘rust-colored’’
complexion (sometimes called ‘‘red Ibos’’). As part of an investigation
of the phenotypic expression of MC1R variants in a black
population we have examined MC1R sequence and hair melanins
in four Jamaican ‘‘redheads’’. This study was approved by the University
of theWest Indies/University Hospital of theWest Indies
Ethics Committee.
Samples were obtained from four redheads (ages 3, 11, 30, and
32 y; two boys and two women, respectively) and also from the
mothers of the two boys. DNA extraction from whole blood, sequencing,
and analysis of hair melanins were all carried out using
previously described methods (Sambrook et al, 1989; Ito and
Wakamatsu, 1994; Wakamatsu et al, 2002). Hair melanins were
analyzed in three of the redheads and are expressed as the logarithm
to the base 10 of the concentrations (ng per mg of hair sample)
of eumelanin and pheomelanin.
Sequencing of MC1R revealed that all of the redheads were
compound heterozygotes for variants that are either known, or
predicted to disrupt MC1R function. MC1R genotypes were as
follows (variant positions compared with human consensus sequence:
GenBank accession no. X65634): subject 1, Gly89Arg/
Arg151Cys (his mother is heterozygous for the Arg151Cys variant);
subject 2, 23 STOP/Arg160Trp (his mother is heterozygous
for the 23 STOP variant); subject 3, Asp294His/frameshift at codon
195; subject 4, 23 STOP/Arg151Cys. Hair melanins for subjects
1, 2, and 3 were as follows: log eumelanin 8.3, 8.3, 7.6; log
pheomelanin 4.2, 6.6, 6.5. All of these values are within the range
seen in a white UK sample of MC1R homozygotes selected on
the basis of the red hair phenotype: average log eumelanin 7.570.6;
average log pheomelanin 6.070.9 (Rees et al, unpublished data).
This is one of the ¢rst studies that has examined MC1R variants
and redheaded phenotypes in individuals from a black population
(i.e., with West African ancestry) and, although small,
we think it is of potential interest. The phenotype, which is anecdotally
uncommon (but from our observations cannot be rare), is
striking; it is very easy to distinguish these individuals from black
persons of lighter or darker complexion because there is a reddish-
orange/rust-colored hue to the skin.
There are a number of conclusions we can draw. First, red hair
in this group, as well as in Caucasians, can be accounted for in
terms of mutation of the MC1R: the changes at codons 151, 160,
and 294 are well known (Harding et al, 2000; Schi˛th et al, 1999),
and we have seen the codon 23 stop (as a heterozygous change
only) in another African without red hair. These data suggest the
possibility of a substantial sampling of Caucasian diversity at
MC1R among Jamaican redheads, augmented from an unknown
(possiblyAfrican) source for the 23 stop variant. Second, the melanin
values are within the range seen in white UK individuals of
equivalent MC1R status. This suggests that even on a di¡erent
genetic background MC1R variants exert a signi¢cant phenotypic
e¡ect. Thus, although we assume that there is admixture at
loci other than MC1R, the high penetrance observed is relevant
to studies seeking to explain the evolution of world-wide variation
in skin and hair color. Further studies in Jamaica and in other
African-descent populations are required; particularly with respect
to the presence of a heterozygote e¡ect and sun sensitivity
