The genetics of sun sensitivity in humans

被引:212
作者
Rees, JL [1 ]
机构
[1] Univ Edinburgh, Syst Grp, Grant Chair Dermatol, Edinburgh EH3 9HA, Midlothian, Scotland
基金
英国惠康基金;
关键词
D O I
10.1086/425285
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a key marker of sun sensitivity, is less heritable. Despite a large number of murine coat-color mutations, only one gene in humans, the melanocortin 1 receptor (MC1R), is known to account for substantial variation in skin and hair color and in skin cancer incidence. MC1R encodes a 317-amino acid G-coupled receptor that controls the relative amounts of the two major melanin classes, eumelanin and pheomelanin. Most persons with red hair are homozygous for alleles of the MC1R gene that show varying degrees of diminished function. More than 65 human MC1R alleles with nonsynonymous changes have been identified, and current evidence suggests that many of them vary in their physiological activity, such that a graded series of responses can be achieved on the basis of (i) dosage effects (of one or two alleles) and (ii) individual differences in the pharmacological profile in response to ligand. Thus, a single locus, identified within a Mendelian framework, can contribute significantly to human pigmentary variation.
引用
收藏
页码:739 / 751
页数:13
相关论文
共 117 条
[1]   Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population [J].
Akey, JM ;
Wang, H ;
Xiong, M ;
Wu, H ;
Liu, W ;
Shriver, MD ;
Jin, L .
HUMAN GENETICS, 2001, 108 (06) :516-520
[2]   Ethnic variation in tyrosinase and TYRP1 expression in photoexposed and photoprotected human skin [J].
Alaluf, S ;
Barrett, K ;
Blount, M ;
Carter, N .
PIGMENT CELL RESEARCH, 2003, 16 (01) :35-42
[3]   Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin [J].
Alaluf, S ;
Atkins, D ;
Barrett, K ;
Blount, M ;
Carter, N ;
Heath, A .
PIGMENT CELL RESEARCH, 2002, 15 (02) :112-118
[4]   The impact of epidermal melanin on objective measurements of human skin colour [J].
Alaluf, S ;
Atkins, D ;
Barrett, K ;
Blount, M ;
Carter, N ;
Heath, A .
PIGMENT CELL RESEARCH, 2002, 15 (02) :119-126
[5]   Variation in melanin content and composition in type V and VI photoexposed and photoprotected human skin: The dominant role of DHI [J].
Alaluf, S ;
Heath, A ;
Carter, N ;
Atkins, D ;
Mahalingam, H ;
Barrett, K ;
Kolb, R ;
Smit, N .
PIGMENT CELL RESEARCH, 2001, 14 (05) :337-347
[6]   What controls variation in human skin color? [J].
Barsh, GS .
PLOS BIOLOGY, 2003, 1 (01) :19-22
[7]   The genetics of pigmentation: From fancy genes to complex traits [J].
Barsh, GS .
TRENDS IN GENETICS, 1996, 12 (08) :299-305
[8]   The melanocortin-1-receptor gene is the major freckle gene [J].
Bastiaens, M ;
ter Huurne, J ;
Gruis, N ;
Bergman, W ;
Westendorp, R ;
Vermeer, BJ ;
Bavinck, JNB .
HUMAN MOLECULAR GENETICS, 2001, 10 (16) :1701-1708
[9]   Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair [J].
Bastiaens, MT ;
ter Huurne, JAC ;
Kielich, C ;
Gruis, NA ;
Westendorp, RGJ ;
Vermeer, BJ ;
Bavinck, NJB .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (04) :884-894
[10]   The color loci of mice - A genetic century [J].
Bennett, DC ;
Lamoreux, ML .
PIGMENT CELL RESEARCH, 2003, 16 (04) :333-344