Human pigmentation genes: identification, structure and consequences of polymorphic variation

Sturm, Richard A.; Teasdale, Rohan D.; Box, Neil F.

doi:10.1016/s0378-1119(01)00694-1

Cited by 338 publications

(282 citation statements)

References 73 publications

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“…The OCA2 gene encodes a protein that is an integral part of the melanosomal membrane and is responsible for regulation of pH inside the melanosome, [55][56][57] which, in consequence, has an influence on the activity of the enzyme tyrosinase, which has a crucial role in the synthesis of the pigment melanin. The important role of OCA2 in eye colour determination was confirmed in many studies, 11,13,28,31,[58][59][60][61] and further investigations revealed that regulation of OCA2 expression through the neighbouring HERC2 gene might have a crucial role. 16,20 A functional effect was assigned to the rs12913832 position located in a conservative segment of the intron 86 of the HERC2 gene, which contains transcription factor-binding sites.…”

Section: Discussionmentioning

confidence: 82%

Gene–gene interactions contribute to eye colour variation in humans

et al. 2011

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Prediction of phenotypes from genetic data is considered to be the first practical application of data gained from association studies, with potential importance for medicine and the forensic sciences. Multiple genes and polymorphisms have been found to be associated with variation in human pigmentation. Their analysis enables prediction of blue and brown eye colour with a reasonably high accuracy. More accurate prediction, especially in the case of intermediate eye colours, may require better understanding of gene-gene interactions affecting this polygenic trait. Using multifactor dimensionality reduction and logistic regression methods, a study of gene-gene interactions was conducted based on variation in 11 known pigmentation genes examined in a cohort of 718 individuals of European descent. The study revealed significant interactions of a redundant character between the HERC2 and OCA2 genes affecting determination of hazel eye colour and between HERC2 and SLC24A4 affecting determination of blue eye colour. Our research indicates interactive effects of a synergistic character between HERC2 and OCA2, and also provides evidence for a novel strong synergistic interaction between HERC2 and TYRP1, both affecting determination of green eye colour.

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Section: Discussionmentioning

confidence: 82%

Gene–gene interactions contribute to eye colour variation in humans

et al. 2011

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“…The overall frequencies of nucleotide substitutions in our test population were counted as 31% for A/G, 36.3% for C/T, 10% for C/G, 9.3% for T/G, 7.3% for A/C, and 6% for A/T; transitions occurred 2.1 times more frequently than transversions. By comparing SNPs detected in this study with previous reports from elsewhere (Sturm et al 2001;Lubrano-Berthelier et al 2003;Schalin-Jantti et al 2003) or with the dbSNP database at NCBI, we were able to consider 132 of the 300 SNPs (44%) to be novel as of the end of December 2003. We also identified two novel nonsense mutations in the Japanese healthy donors.…”

Section: Resultsmentioning

confidence: 99%

Catalog of 300 SNPs in 23 genes encoding G-protein coupled receptors

et al. 2004

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We previously published a series of detailed maps of single nucleotide polymorphisms (SNPs) in the genomic regions of 209 gene loci encoding drug metabolizing enzymes, transporters, receptors, and other potential drug targets. In addition to the maps reported earlier, we provide here high-resolution SNP maps of 23 genes encoding G-protein coupled receptors in the Japanese population. A total of 300 SNPs were identified through screening of these loci; 83 in four adenosine receptor family genes, 45 in three adrenergic receptor family genes, 22 in three EDG receptor family genes, 29 in three melanocortin receptor family genes, 22 in two somatostatin receptor family genes, 21 in five anonymous G protein-coupled receptor family genes, and 78 in the others (AVPR1B, OXTR, and TNFRSF1A). We also discovered a total of 33 genetic variations of other types. Of the 300 SNPs, 132 (44%) appeared to be novel on the basis of comparisons with the dbSNP database of the National Center for Biotechnology Information (US) or with previous publications. The maps constructed in this study will serve as an additional resource for studies of complex genetic diseases and drug-response phenotypes to be mapped by linkage-disequilibrium association analyses.

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“…In other words, the influence of other genes could mask the recessive action of high-penetrance MC1R alleles and lead to the low frequency of atrisk phototypes (i.e I-II maximum 27%), and this may contribute to the slightly lower occurrence and penetrance for melanoma seen in Liguria. Indeed, it has been suggested that mutations in the MC1R promoter may be important for normal pigmentation variation (Makova et al, 2001), and several other genes (alpha-MSH, TYRP1, TYRP2, SILV, P-gene) have been identified that are also likely to play a role in normal pigmentation variation, either by controlling the rate and type of melanin produced, or by exerting an effect on the melanin biosynthetic pathway (Sturm et al, 2001). In view of the features we identified in our small sample, the Ligurian population could be a useful pool to evaluate the role of those genes in modification of penetrance of at-risk phenotypes.…”

Section: Discussionmentioning

confidence: 99%