Document Detail

Molecular genetics of human pigmentation diversity.
MedLine Citation:
PMID:  19297406     Owner:  NLM     Status:  MEDLINE    
The genetic basis underlying normal variation in the pigmentary traits of skin, hair and eye colour has been the subject of intense research directed at understanding the diversity seen both between and within human populations. A combination of approaches have been used including comparative genomics of candidate genes and the identification of regions of the human genome under positive selection, together with genome-wide and specific allele association studies. Independent selection for different pigmentation gene sets has been found between Asian, European and African populations. Several genome-wide association studies for pigmentation have now been conducted and identified single nucleotide polymorphism (SNP) markers in known, TYR, TYRP1, OCA2, SLC45A2, SLC24A5, MC1R, ASIP, KITLG and previously unknown SLC24A4, IRF4, TPCN2, candidate genes. The contribution of SNP polymorphisms present in populations from South Asia have been tested and alleles found at TYR, SLC45A2 and SLC24A5 can largely account for differences between those of darkest and lightest skin reflectance using a simple additive model. Skin and hair colour associations in Europeans are found within a range of pigmentation gene alleles, whereas blue-brown eye colour can be explained by a single SNP proposed to regulate OCA2 expression. Functional testing of variant alleles has begun to connect phenotype correlations with biological differences. Variant MC1R alleles show direct correlations between the biochemical signalling properties of the encoded receptor and the red-hair fair skin pigmentation phenotype. Direct testing of a range of clonal melanocyte cultures derived from donor skin tissue characterized for three causal SNPs within SLC45A2, SLC24A5 and OCA2 has assessed their impact on melanin content and tyrosinase enzyme activity. From a culmination of genetic and functional studies, it is apparent that a number of genes impacting melanosome biogenesis or the melanin biosynthetic pathway are candidates to explain the diversity seen in human pigmentation.
Richard A Sturm
Related Documents :
11317366 - Identification of four novel polymorphisms in the calcitonin/alpha-cgrp (calca) gene an...
15496426 - Polymorphisms in the prostaglandin e2 receptor subtype 2 gene confer susceptibility to ...
15911586 - Effects of natural selection on interpopulation divergence at polymorphic sites in huma...
22266406 - Evaluation of the warfarin-resistance polymorphism, vkorc1 asp36tyr, and its effect on ...
17473736 - Normal tension glaucoma is not associated with the interleukin -1alpha (-889) genetic p...
15009726 - An assessment of a variant of the dna repair gene xrcc3 as a possible nevus or melanoma...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Human molecular genetics     Volume:  18     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-19     Completed Date:  2009-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  R9-17     Citation Subset:  IM    
Melanogenix Group, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Eye Color / genetics*
Genome-Wide Association Study
Hair Color / genetics*
Melanins / biosynthesis
Polymorphism, Single Nucleotide
Skin Pigmentation / genetics*
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Constitutional aneuploidy and cancer predisposition.
Next Document:  Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment.