Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression
Abstract
The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86 of HERC2. The brown eye color allele of rs12913832 is highly conserved throughout a number of species. As shown by a Luciferase assays in cell cultures, the element significantly reduces the activity of the OCA2 promoter and electrophoretic mobility shift assays demonstrate that the two alleles bind different subsets of nuclear extracts. One single haplotype, represented by six polymorphic SNPs covering half of the 3' end of the HERC2 gene, was found in 155 blue-eyed individuals from Denmark, and in 5 and 2 blue-eyed individuals from Turkey and Jordan, respectively. Hence, our data suggest a common founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The allele (G) at rs12913832 near the OCA2 gene has a proven association to blue eye color in individuals of European descent.
“an allele (G) at rs12913832 near the OCA2 gene, with a proven association to blue eye color in individuals of European descent40”
From Ancient DNA from Chalcolithic Israel reveals the role of population mixture in cultural transformation (2018) · cites this paper as [40]
The derived allele (G) at rs12913832 is recessive and is associated with blue eye color.
“The derived allele (G) at rs12913832 is recessive and is associated with blue eye color.”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [33]
rs1667394 is also in LD with rs12913832 (D' = 1, r2 = 0.65), which was not genotyped in the study but is thought to be the likely causative variant for blue versus brown eye color by genetic and functional analyses.
“rs1667394 is also in LD with rs12913832 (D’ = 1, r2 = 0.65), which was not genotyped in our study but is thought to be the likely causative variant for blue versus brown eye color by genetic and functional analyses [33], [34].”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [33]
Cites
The History and Geography of Human Genes
Cavalli-Sforza, L. L., Menozzi, P., & Piazza, A. (2018) · Princeton University Press eBooks · doi:10.2307/j.ctv301gjp · Cited by 3,175 · see citing works
Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL
Heinemeyer, T. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.362 · Cited by 1,462 · see citing works
Avoiding Recomputation in Linkage Analysis
Schäffer, A. A., Gupta, S. K., Shriram, K. M. P., & Cottingham, R. W. (1994) · Human Heredity · doi:10.1159/000154222 · Cited by 668 · see citing works
Long-range chromatin regulatory interactions in vivo
Carter, D., Chakalova, L., Osborne, C. S., Dai, Y.-F., & Fraser, P. (2002) · Nature Genetics · doi:10.1038/ng1051 · Cited by 663 · see citing works
The history and geography of human genes
Mace, R. H. (1995) · Trends in Ecology & Evolution · doi:10.1016/s0169-5347(00)89087-4 · Cited by 644 · see citing works
Human pigmentation genes: identification, structure and consequences of polymorphic variation
Sturm, R. A., Teasdale, R. D., & Box, N. F. (2001) · Gene · doi:10.1016/s0378-1119(01)00694-1 · Cited by 388 · see citing works
Combinatorial control of gene expression
Reményi, A., Schöler, H. R., & Wilmanns, M. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb820 · Cited by 272 · see citing works
Ancāns, J., Tobin, D. J., Hoogduijn, M. J., Smit, N. P. M., Wakamatsu, K., & Thody, A. J. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5251 · Cited by 242 · see citing works
Duffy, D. L., Montgomery, G. W., Chen, W., Zhao, Z. Z., Le, L., James, M. R., Hayward, N. K., Martin, N. G., & Sturm, R. A. (2007) · The American Journal of Human Genetics · doi:10.1086/510885 · Cited by 240 · see citing works
Lee, S.-T., Nicholls, R., Jong, M. T. C., Fukai, K., & Spritz, R. (1995) · Genomics · doi:10.1016/0888-7543(95)80220-g · Cited by 210 · see citing works
An upstream polymorphism associated with lactase persistence has increased enhancer activity
Troelsen, J. T., Olsen, J., Møller, J., & Sjöström, H. (2003) · Gastroenterology · doi:10.1053/j.gastro.2003.09.031 · Cited by 194 · see citing works
Self-citationAberrant pH of Melanosomes in Pink-Eyed Dilution (p) Mutant Melanocytes
Puri, N., Gardner, J. M., & Brilliant, M. H. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00108.x · Cited by 172 · see citing works
Sequences associated with human iris pigmentation
Frudakis, T., Thomas, M., Gaskin, Z., Venkateswarlu, K., Chandra, K. S., Ginjupalli, S., Gunturi, S., Natrajan, S., Ponnuswamy, V. K., & Ponnuswamy, K. N. (2003) · Genetics · doi:10.1093/genetics/165.4.2071 · Cited by 153 · see citing works
Toyofuku, K., Valencia, J. C., Kushimoto, T., Costin, G., Virador, V. M., Vieira, W. D., Ferrans, V. J., & Hearing, V. J. (2002) · Pigment Cell Research · doi:10.1034/j.1600-0749.2002.02007.x · Cited by 140 · see citing works
A Genome Scan for Eye Color in 502 Twin Families: Most Variation is due to a QTL on Chromosome 15q
Zhu, G., Evans, D. M., Duffy, D. L., Montgomery, G. W., Medland, S. E., Gillespie, N. A., Ewen, K. R., Jewell, M., Liew, Y., Hayward, N. K., et al. (2004) · Twin Research · doi:10.1375/twin.7.2.197 · Cited by 119 · see citing works
P gene as an inherited biomarker of human eye color.
Rebbeck, T. R., Kanetsky, P. A., Walker, A. H., Holmes, R., Halpern, A. C., Schuchter, L. M., Elder, D. E., & Guerry, D. (2002) · PubMed · Cited by 96 · see citing works
A very large protein with diverse functional motifs is deficient in rjs (runty, jerky, sterile) mice
Lehman, A. L., Nakatsu, Y., Ching, A., Bronson, R. T., Oakey, R. J., Keiper‐Hrynko, N. M., Finger, J. N., Durham‐Pierre, D., Horton, D. B., Newton, J. M., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9436 · Cited by 95 · see citing works
Eiberg, H., & Mohr, J. (1996) · European Journal of Human Genetics · doi:10.1159/000472205 · Cited by 71 · see citing works
Self-citationMultilocus OCA2 genotypes specify human iris colors
Frudakis, T., Terravainen, T., & Thomas, M. J. (2007) · Human Genetics · doi:10.1007/s00439-007-0401-8 · Cited by 67 · see citing works
Lamoreux, M. L., Zhou, B.-K., Rosemblat, S., & Orlow, S. J. (1995) · Pigment Cell Research · doi:10.1111/j.1600-0749.1995.tb00673.x · Cited by 62 · see citing works
Estimation of the Age of the Ancestral Arginine3500→ Glutamine Mutation in Human ApoB-100
Myant, N. B., Forbes, S. A., Day, I. N. M., & Gallagher, J. J. (1997) · Genomics · doi:10.1006/geno.1997.4898 · Cited by 62 · see citing works
Novak, E., Reddington, M., Zhen, L., Stenberg, P. E., Jackson, C., Mp, M., & Swank, R. T. (1995) · Blood · doi:10.1182/blood.v85.7.1781.bloodjournal8571781 · Cited by 59 · see citing works
Structure of the Highly Conserved HERC2 Gene and of Multiple Partially Duplicated Paralogs in HumanPreprint
Ji, Y., Rebert, N. A., Joslin, J. M., Higgins, M. J., Schultz, R. A., & Nicholls, R. D. (2000) · Genome Research · doi:10.1101/gr.10.3.319 · Cited by 57 · see citing works
Eiberg, H., Nielsen, L. S., Klausen, J., Dahlén, M., Kristensen, M., Bisgaard, M. L., Møller, N., & Mohr, J. (1989) · Clinical Genetics · doi:10.1111/j.1399-0004.1989.tb02951.x · Cited by 49 · see citing works
Self-citationRussell, L. B., Montgomery, C. S., Cacheiro, N. L. A., & Johnson, D. K. (1995) · Genetics · doi:10.1093/genetics/141.4.1547 · Cited by 48 · see citing works
Voltage-Gated Potassium Channel Genes Are Clustered in Paralogous Regions of the Mouse Genome
Lock, L. F., Gilbert, D. J., Street, V. A., Migeon, M. B., Jenkins, N. A., Copeland, N. G., & Tempel, B. L. (1994) · Genomics · doi:10.1006/geno.1994.1188 · Cited by 39 · see citing works
Replicated Linkage for Eye Color on 15q Using Comparative Ratings of Sibling Pairs
Danielle Posthuma, B., Visscher, P. M., Willemsen, G. A. H. M., Zhu, G., Martin, N. G., Slagboom, P. E., de Geus, E. J. C., & Boomsma, D. I. (2005) · Behavior Genetics · doi:10.1007/s10519-005-9007-x · Cited by 28 · see citing works
An enhancer activates the pig lactase phlorizin hydrolase promoter in intestinal cells
Troelsen, J. T., Mitchelmore, C., & Olsen, J. (2003) · Gene · doi:10.1016/s0378-1119(02)01232-5 · Cited by 18 · see citing works
Self-citationNishimura, G., Harigaya, A., Kuwashima, M., & Kuwashima, S. (1997) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19970711)71:1
Flagged first, then by citations
1 of the 30 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Genome-wide patterns of selection in 230 ancient Eurasians
Mathieson, I., Lazaridis, I., Rohland, N., Mallick, S., Patterson, N., Roodenberg, S. A., Harney, E., Stewardson, K., Fernandes, D., Novak, M., et al. (2015) · Nature · doi:10.1038/nature16152 · Cited by 1,515 · see citing works
Ancient human genomes suggest three ancestral populations for present-day Europeans
Lazaridis, I., Patterson, N., Mittnik, A., Renaud, G., Mallick, S., Kirsanow, K., Sudmant, P. H., Schraiber, J. G., Castellano, S., Lipson, M., et al. (2014) · Nature · doi:10.1038/nature13673 · Cited by 1,357 · see citing works
Programmed DNA destruction by miniature CRISPR-Cas14 enzymes
Harrington, L., Burstein, D., Chen, J. S., Páez-Espino, D., Ma, E., Witte, I. P., Cofsky, J. C., Kyrpides, N., Banfield, J., & Doudna, J. (2018) · Science · doi:10.1126/science.aav4294 · Cited by 1,106 · see citing works
Physiological functions of the HECT family of ubiquitin ligases
Rotin, D., & Kumar, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2690 · Cited by 1,063 · see citing works
The genetic history of Ice Age Europe
Fu, Q., Posth, C., Hajdinjak, M., Petr, M., Mallick, S., Fernandes, D., Furtwängler, A., Haak, W., Meyer, M., Mittnik, A., et al. (2016) · Nature · doi:10.1038/nature17993 · Cited by 959 · see citing works
Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding
Xue, Y., Prado-Martinez, J., Sudmant, P. H., Narasimhan, V., Ayub, Q., Szpak, M., Frandsen, P., Chen, Y., Yngvadottir, B., Cooper, D. N., et al. (2015) · Science · doi:10.1126/science.aaa3952 · Cited by 473 · see citing works
Kayser, M. (2015) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2015.02.003 · Cited by 447 · see citing works
The HIrisPlex system for simultaneous prediction of hair and eye colour from DNA
Walsh, S., Liu, F., Wollstein, A., Kovatsi, L., Ralf, A., Kosiniak-Kamysz, A., Branicki, W., & Kayser, M. (2013) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2012.07.005 · Cited by 428 · see citing works
Walsh, S., Liu, F., Ballantyne, K., van Oven, M., Lao, O., & Kayser, M. (2011) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2010.02.004 · Cited by 372 · see citing works
Molecular genetics of human pigmentation diversity
Sturm, R. A. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp003 · Cited by 379 · see citing works
Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo
Jin, Y., Birlea, S. A., Fain, P. R., Ferrara, T. M., Ben, S., Riccardi, S. L., Cole, J. B., Gowan, K., Holland, P. J., Bennett, D. C., et al. (2012) · Nature Genetics · doi:10.1038/ng.2272 · Cited by 352 · see citing works
Loci associated with skin pigmentation identified in African populations
Crawford, N. G., Kelly, D., Hansen, M. E. B., Beltrame, M., Fan, S.-H., Bowman, S. L., Jewett, E., Ranciaro, A., Thompson, S., Lo, Y., et al. (2017) · Science · doi:10.1126/science.aan8433 · Cited by 345 · see citing works
Chaitanya, L., Breslin, K., Zuñiga, S., Wirken, L., Pośpiech, E., Kukla-Bartoszek, M., Sijen, T., Knijff, P. D., Liu, F., Branicki, W., et al. (2018) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2018.04.004 · Cited by 335 · see citing works
“Over the last 10 years, candidate gene association studies and genome-wide association studies (GWASs), as well as subsequent prediction analyses, have established various EVC-predictive SNPs and prediction models, most notably for human pigmentation traits [8-30].”
BackgroundForensically Relevant SNP Classes
Budowle, B., & van Daal, A. (2008) · BioTechniques · doi:10.2144/000112806 · Cited by 298 · see citing works
Early Neolithic genomes from the eastern Fertile Crescent
Broushaki, F., Thomas, M. G., Link, V., López, S., van Dorp, L., Kirsanow, K., Hofmanová, Z., Diekmann, Y., Cassidy, L. M., Díez-del-Molino, D., et al. (2016) · Science · doi:10.1126/science.aaf7943 · Cited by 288 · see citing works
Eye color and the prediction of complex phenotypes from genotypes.
Liu, F., van Duijn, K., Vingerling, J., Hofman, A., Uitterlinden, A., Janssens, A. C., & Kayser, M. (2009) · Current Biology · doi:10.1016/j.cub.2009.01.027 · Cited by 285 · see citing works
Visser, M., Kayser, M., & Palstra, R.-J. T. S. (2012) · Genome Research · doi:10.1101/gr.128652.111 · Cited by 278 · see citing works
Kayser, M., & Schneider, P. (2009) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2009.01.012 · Cited by 261 · see citing works
Wilde, S., Timpson, A., Kirsanow, K., Kaiser, E., Kayser, M., Unterländer, M., Hollfelder, N., Potekhina, I. D., Schier, W., Thomas, M. G., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316513111 · Cited by 257 · see citing works
Pleistocene North African genomes link Near Eastern and sub-Saharan African human populations
van de Loosdrecht, M. S., Bouzouggar, A., Humphrey, L., Posth, C., Barton, N., Aximu‐Petri, A., Nickel, B., Nagel, S., Talbi, E. H., Hajraoui, M. A. E., et al. (2018) · Science · doi:10.1126/science.aar8380 · Cited by 241 · see citing works
Walsh, S., Chaitanya, L., Clarisse, L., Wirken, L., Draus-Barini, J., Kovatsi, L., Maeda, H., Ishikawa, T., Sijen, T., de Knijff, P., et al. (2014) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2013.12.006 · Cited by 240 · see citing works
Genetics of human iris colour and patterns
Sturm, R. A., & Larsson, M. (2009) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00606.x · Cited by 239 · see citing works
Duffy, D. L., Zhao, Z., Sturm, R. A., Hayward, N. K., Martin, N. G., & Montgomery, G. W. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.258 · Cited by 206 · see citing works
Genetics of pigmentation in skin cancer — A review
Scherer, D., & Kumar, R. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2010.06.002 · Cited by 203 · see citing works
Application of Next-Generation Sequencing Technology in Forensic Science
Yang, Y., Xie, B., & Yan, J. (2014) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2014.09.001 · Cited by 204 · see citing works
Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci
Liu, F., Wollstein, A., Hysi, P. G., Ankra-Badu, G. A., Spector, T. D., Park, D., Zhu, G., Larsson, M., Duffy, D. L., Montgomery, G. W., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000934 · Cited by 191 · see citing works
Model-based prediction of human hair color using DNA variants
Branicki, W., Liu, F., van Duijn, K., Draus‐Barini, J., Pośpiech, E., Walsh, S., Kupiec, T., Wojas‐Pelc, A., & Kayser, M. (2011) · Human Genetics · doi:10.1007/s00439-010-0939-8 · Cited by 188 · see citing works
Bellone, R. R., Brooks, S. A., Sandmeyer, L. S., Murphy, B. A., Forsyth, G. W., Archer, S., Bailey, E., & Grahn, B. H. (2008) · Genetics · doi:10.1534/genetics.108.088807 · Cited by 174 · see citing works
Liu, F., Visser, M., Duffy, D. L., Hysi, P. G., Jacobs, L. C., Lao, O., Zhong, K., Walsh, S., Chaitanya, L., Wollstein, A., et al. (2015) · Human Genetics · doi:10.1007/s00439-015-1559-0 · Cited by 172 · see citing works
Global skin colour prediction from DNA
Walsh, S., Chaitanya, L., Breslin, K., Muralidharan, C., Bronikowska, A., Pośpiech, E., Koller, J., Kovatsi, L., Wollstein, A., Branicki, W., et al. (2017) · Human Genetics · doi:10.1007/s00439-017-1808-5 · Cited by 159 · see citing works
Further development of forensic eye color predictive tests
Ruíz, Y., Phillips, C., Gómez‐Tato, A., Álvarez‐Dios, J. A., de Cal, M. C., Cruz, R., Maroñas, O., Söchtig, J., Fondevila, M., Rodríguez‐Cid, M. J., et al. (2012) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2012.05.009 · Cited by 158 · see citing works
Heath, S. C., Gut, I. G., Brennan, P., McKay, J., Bencko, V., Fabiánová, E., Foretová, L., Georges, M., Janout, V., Kabesch, M., et al. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.210 · Cited by 160 · see citing works
DNA-based eye colour prediction across Europe with the IrisPlex system
Walsh, S., Wollstein, A., Liu, F., Chakravarthy, U., Rahu, M., Seland, J. H., Soubrane, G., Tomazzoli, L., Topouzis, F., Vingerling, J. R., et al. (2011) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2011.07.009 · Cited by 154 · see citing works
Ancestry analysis in the 11-M Madrid bomb attack investigation
Phillips, C., Prieto, L., Fondevila, M., Salas, A., Gómez-Tato, A., Álvarez-Dios, J., Alonso, A., Blanco-Verea, A., Brión, M., Montesino, M., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006583 · Cited by 149 · see citing works
Harney, É., May, H., Shalem, D., Rohland, N., Mallick, S., Lazaridis, I., Sarig, R., Stewardson, K., Nordenfelt, S., Patterson, N., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05649-9 · Cited by 141 · see citing works
Genome-Wide Association Study of Tanning Phenotype in a Population of European Ancestry
Nan, H., Kraft, P., Qureshi, A. A., Guo, Q., Chen, C., Hankinson, S. E., Hu, F. B., Thomas, G. D., Hoover, R. N., Chanock, S. J., et al. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.62 · Cited by 139 · see citing works
Ancient DNA provides new insights into the history of south Siberian Kurgan people
Keyser, C., Bouakaze, C., Crubézy, É., Nikolaev, V. G., Montagnon, D., Reis, T. M., & Ludes, B. (2009) · Human Genetics · doi:10.1007/s00439-009-0683-0 · Cited by 138 · see citing works
Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability
Morgan, M. D., Pairo‐Castineira, E., Rawlik, K., Canela‐Xandri, O., Rees, J., Sims, D., Tenesa, A., & Jackson, I. J. (2018) · Nature Communications · doi:10.1038/s41467-018-07691-z · Cited by 133 · see citing works
An intracellular anion channel critical for pigmentation
Bellono, N. W., Escobar, I. E., Lefkovith, A. J., Marks, M. S., & Oancea, E. (2014) · eLife · doi:10.7554/elife.04543 · Cited by 136 · see citing works
The RCC1 superfamily: From genes, to function, to disease
Hadjebi, O., Casas‐Terradellas, E., García-Gonzalo, F. R., & Rosa, J. L. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.03.015 · Cited by 133 · see citing works
A global view of the OCA2-HERC2 region and pigmentation
Donnelly, M. P., Paschou, P., Grigorenko, E., Gurwitz, D., Barta, C., Lu, R.-B., Zhukova, O. V., Kim, J.-J., Siniscalco, M., New, M., et al. (2012) · Human Genetics · doi:10.1007/s00439-011-1110-x · Cited by 131 · see citing works
Edwards, M., Bigham, A., Tan, J., Li, S., Gozdzik, A., Ross, K., Jin, L., & Parra, E. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000867 · Cited by 128 · see citing works
Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis
Gerstenblith, M. R., Shi, J., & Landi, M. T. (2010) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2010.00730.x · Cited by 128 · see citing works
The genetic and evolutionary basis of colour variation in vertebrates
Hofreiter, M., & Schöneberg, T. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0333-7 · Cited by 128 · see citing works
CRISPR mutagenesis confirms the role of oca2 in melanin pigmentation in Astyanax mexicanus
Klaassen, H., Wang, Y., Adamski, K., Rohner, N., & Kowalko, J. E. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.03.014 · Cited by 119 · see citing works
Prediction of eye and skin color in diverse populations using seven SNPs
Spichenok, O., Budimlija, Z. M., Mitchell, A. A., Jenny, A., Kovacevic, L., Marjanovic, D., Caragine, T., Prinz, M., & Wurmbach, E. (2011) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2010.10.005 · Cited by 121 · see citing works
Eurasiaplex: A forensic SNP assay for differentiating European and South Asian ancestries
Phillips, C., Freire-Aradas, A., Kriegel, A. K., Fondevila, M., Bülbül, Ö., Santos, C., Rech, F. S., Cárceles, M. D. P., Carracedo, Á., Schneider, P. M., et al. (2013) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2013.02.010 · Cited by 118 · see citing works
Membrane transport proteins in melanosomes: Regulation of ions for pigmentation
Wiriyasermkul, P., Moriyama, S., & Nagamori, S. (2020) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2020.183318 · Cited by 118 · see citing works
SLC45A2: a novel malignant melanoma-associated gene
Fernández, L. P., Milne, R. L., Pita, G., Avilés, J. A., Lázaro, P., Benitez, J. J., & Ribas, G. (2008) · Human Mutation · doi:10.1002/humu.20804 · Cited by 115 · see citing works
Genotype–phenotype associations and human eye color
White, D., & Rabago-Smith, M. (2010) · Journal of Human Genetics · doi:10.1038/jhg.2010.126 · Cited by 109 · see citing works
Candille, S. I., Absher, D. M., Beleza, S., Bauchet, M., McEvoy, B., Garrison, N. A., Li, J. Z., Myers, R. M., Barsh, G. S., Tang, H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048294 · Cited by 111 · see citing works
Branicki, W., Brudnik, U., & Wojas‐Pelc, A. (2009) · Annals of Human Genetics · doi:10.1111/j.1469-1809.2009.00504.x · Cited by 108 · see citing works
Development of a forensic skin colour predictive test
Maroñas, O., Phillips, C., Söchtig, J., Gómez‐Tato, A., Cruz, R., Álvarez‐Dios, J. A., de Cal, M. C., Ruíz, Y., Fondevila, M., Carracedo, Á., et al. (2014) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2014.06.017 · Cited by 100 · see citing works
Capellini, T. D., Chen, H., Cao, J., Doxey, A. C., Kiapour, A. M., Schoor, M., & Kingsley, D. M. (2017) · Nature Genetics · doi:10.1038/ng.3911 · Cited by 96 · see citing works
Testing for ancient selection using cross-population allele frequency differentiation
Racimo, F. (2016) · Genetics · doi:10.1534/genetics.115.178095 · Cited by 96 · see citing works
Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma
Asgari, M. M., Wang, W., Ioannidis, N. M., Itnyre, J., Hoffmann, T. J., Jorgenson, E., & Whittemore, A. S. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.01.013 · Cited by 93 · see citing works
Human eye colour and HERC2, OCA2 and MATP
Mengel‐From, J., Børsting, C., Sánchez, J. J. M., Eiberg, H., & Morling, N. (2010) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2009.12.004 · Cited by 92 · see citing works
Self-citationTeruel, B. M., Parra, E. J., Fuentes-Smith, E., Salas, A., Buttenschøn, H. N., Demontis, D., Torres, M. L., Padrón, L. C. M., Gómez-Cabezas, E. J., Álvarez‐Iglesias, V., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004488 · Cited by 93 · see citing works
Localization of adaptive variants in human genomes using averaged one-dependence estimation
Sugden, L. A., Atkinson, E. G., Fischer, A. P., Rong, S., Henn, B. M., & Ramachandran, S. (2018) · Nature Communications · doi:10.1038/s41467-018-03100-7 · Cited by 88 · see citing works
Harries, L. W., Perry, J. R. B., McCullagh, P. J., & Crundwell, M. C. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-315 · Cited by 89 · see citing works
Association of the SLC45A2 gene with physiological human hair colour variation
Branicki, W., Brudnik, U., Draus‐Barini, J., Kupiec, T., & Wojas‐Pelc, A. (2008) · Journal of Human Genetics · doi:10.1007/s10038-008-0338-3 · Cited by 86 · see citing works
The retinal pigmentation pathway in human albinism: Not so black and white
Bakker, R., Wagstaff, E. L., Kruijt, C. C., Emri, E., van Karnebeek, C., Hoffmann, M. B., Brooks, B. P., Boon, C. J. F., Montoliu, L., van Genderen, M. M., et al. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2022.101091 · Cited by 86 · see citing works
Trustworthy-Looking Face Meets Brown Eyes
Kleisner, K., Priplatova, L., Frost, P., & Flegr, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053285 · Cited by 85 · see citing works
Genetic determinants of hair and eye colours in the Scottish and Danish populations
Mengel-From, J., Wong, T. H., Morling, N., Rees, J., & Jackson, I. (2009) · BMC Genetics · doi:10.1186/1471-2156-10-88 · Cited by 82 · see citing works
Self-citationCis-ruption mechanisms: disruption of cis-regulatory control as a cause of human genetic disease
Kleinjan, D., & Coutinho, P. (2009) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elp022 · Cited by 83 · see citing works
Simcoe, M. J., Valdes, A. M., Liu, F., Furlotte, N. A., Evans, D. M., Hemani, G., Ring, S. M., Smith, G. D., Duffy, D. L., Zhu, G., et al. (2021) · Science Advances · doi:10.1126/sciadv.abd1239 · Cited by 85 · see citing works
Draus-Barini, J., Walsh, S., Pośpiech, E., Kupiec, T., Głąb, H., Branicki, W., & Kayser, M. (2013) · Investigative Genetics · doi:10.1186/2041-2223-4-3 · Cited by 82 · see citing works
Colonna, V., Ayub, Q., Chen, Y., Pagani, L., Luisi, P., Pybus, M., Garrison, E. P., Xue, Y., & Tyler‐Smith, C. (2014) · Genome biology · doi:10.1186/gb-2014-15-6-r88 · Cited by 80 · see citing works
Current aspects of vitiligo genetics
Czajkowski, R., & Męcińska‐Jundziłł, K. (2014) · Advances in Dermatology and Allergology · doi:10.5114/pdia.2014.43497 · Cited by 81 · see citing works
Colorful DNA polymorphisms in humans
Liu, F., Wen, B., & Kayser, M. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.03.013 · Cited by 81 · see citing works
Mutation of HERC2 causes developmental delay with Angelman-like features
Harlalka, G. V., Baple, E. L., Cross, H. E., Kühnle, S., Cubillos‐Rojas, M., Matentzoglu, K., Patton, M. A., Wagner, K., Coblentz, R., Ford, D. L., et al. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101367 · Cited by 79 · see citing works
Sitaram, A., Piccirillo, R., Palmisano, I., Harper, D. C., Dell’Angelica, E. C., Schiaffino, M. V., & Marks, M. S. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-07-0710 · Cited by 77 · see citing works
The history of climate and society: a review of the influence of climate change on the human past
Degroot, D., Anchukaitis, K. J., Tierney, J. E., Riede, F., Manica, A., Moesswilde, E. C., & Gauthier, N. (2022) · Environmental Research Letters · doi:10.1088/1748-9326/ac8faa · Cited by 81 · see citing works
Pigmentation‐related genes and their implication in malignant melanoma susceptibility
Fernández, L. P., Milne, R. L., Pita, G., Floristán, U., Sendagorta, E., Rodríguez, M. F., Avilés, J. A., Martín‐González, M., Lázaro, P., Benitez, J. J., et al. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00846.x · Cited by 74 · see citing works
Skin colour and vitamin D: An update
Hänel, A., & Carlberg, C. (2020) · Experimental Dermatology · doi:10.1111/exd.14142 · Cited by 76 · see citing works
Classification of iris colour: review and refinement of a classification schema
Mackey, D. A., Wilkinson, C. H., Kearns, L. S., & Hewitt, A. W. (2010) · Clinical and Experimental Ophthalmology · doi:10.1111/j.1442-9071.2010.02487.x · Cited by 73 · see citing works
Gene–gene interactions contribute to eye colour variation in humans
Pośpiech, E., Draus‐Barini, J., Kupiec, T., Wojas‐Pelc, A., & Branicki, W. (2011) · Journal of Human Genetics · doi:10.1038/jhg.2011.38 · Cited by 71 · see citing works
Genomic and Strontium Isotope Variation Reveal Immigration Patterns in a Viking Age Town
Krzewińska, M., Kjellström, A., Günther, T., Hedenstierna‐Jonson, C., Zachrisson, T., Omrak, A., Yaka, R., Kılınç, G. M., Somel, M., Sobrado, V., et al. (2018) · Current Biology · doi:10.1016/j.cub.2018.06.053 · Cited by 68 · see citing works
Pośpiech, E., Wojas‐Pelc, A., Walsh, S., Liu, F., Maeda, H., Ishikawa, T., Skowron, M., Kayser, M., & Branicki, W. (2014) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2014.01.012 · Cited by 70 · see citing works
Sitaram, A., Dennis, M. K., Chaudhuri, R., Jesus-Rojas, W. D., Tenza, D., Setty, S. R. G., Wood, C. S., Sviderskaya, E. V., Bennett, D. C., Raposo, G., et al. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-06-0509 · Cited by 69 · see citing works
Mashimo, T., Hadjebi, O., Amair‐Pinedo, F., Tsurumi, T., Vives, F. L., Serikawa, T., Sotelo, C., Guénet, J., & Rosa, J. L. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000784 · Cited by 69 · see citing works
Iris Colour and the Risk of Developing Uveal Melanoma
Houtzagers, L. E., Wierenga, A. P. A., Ruys, A. A. M., Luyten, G. P. M., & Jager, M. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197172 · Cited by 69 · see citing works
Variants of theMATP/SLC45A2gene are protective for melanoma in the French population
Guedj, M., Bourillon, A., Combadière, C., Rodero, M. P., Dieudé, P., Descamps, V., Dupin, N., Wolkenstein, P., Aegerter, P., Lebbé, C., et al. (2008) · Human Mutation · doi:10.1002/humu.20823 · Cited by 67 · see citing works
Direct detection of natural selection in Bronze Age BritainPreprint
Mathieson, I., & Terhorst, J. (2022) · Genome Research · doi:10.1101/gr.276862.122 · Cited by 62 · see citing works
Shades of complexity: New perspectives on the evolution and genetic architecture of human skin
Quillen, E. E., Norton, H. L., Parra, E. J., Lona‐Durazo, F., Ang, K. C., Illiescu, F. M., Pearson, L. N., Shriver, M. D., Lasisi, T., Gokcumen, O., et al. (2019) · American Journal of Physical Anthropology · doi:10.1002/ajpa.23737 · Cited by 67 · see citing works
Bouakaze, C., Keyser, C., Crubézy, É., Montagnon, D., & Ludes, B. (2009) · International Journal of Legal Medicine · doi:10.1007/s00414-009-0348-5 · Cited by 62 · see citing works
Genetic identification of putative remains of the famous astronomer Nicolaus Copernicus
Bogdanowicz, W., Allen, M., Branicki, W., Lembring, M., Gajewska, M., & Kupiec, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901848106 · Cited by 61 · see citing works
Waldman, S., Backenroth, D., Harney, É., Flohr, S., Neff, N. C., Buckley, G. M., Fridman, H., Akbari, A., Rohland, N., Mallick, S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.11.002 · Cited by 63 · see citing works
Verification of eye and skin color predictors in various populations
Pneuman, A., Budimlija, Z. M., Caragine, T. A., Prinz, M., & Wurmbach, E. (2012) · Legal Medicine · doi:10.1016/j.legalmed.2011.12.005 · Cited by 59 · see citing works
Prediction of eye color in the Slovenian population using the IrisPlex SNPs
Kastelic, V., Pośpiech, E., Draus‐Barini, J., Branicki, W., & Drobnič, K. (2013) · Croatian Medical Journal · doi:10.3325/cmj.2013.54.381 · Cited by 59 · see citing works
Olson, M. V. (2012) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090711-163825 · Cited by 57 · see citing works
Andersen, J. D., Johansen, P., Harder, S., Christoffersen, S. R., Delgado, M. C., Henriksen, S. T., Nielsen, M. M. B., Sørensen, E., Ullum, H., Hansen, T. F., et al. (2013) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2013.05.003 · Cited by 58 · see citing works
Self-citationKeating, B. J., Bansal, A. T., Walsh, S., Millman, J. S., Newman, J., Kídd, K. K., Budowle, B., Eisenberg, A. J., Donfack, J., Gasparini, P., et al. (2012) · International Journal of Legal Medicine · doi:10.1007/s00414-012-0788-1 · Cited by 58 · see citing works
Martínez‐Cadenas, C., Peña-Chilet, M., Ibarrola‐Villava, M., & Ribas, G. (2013) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2013.03.007 · Cited by 53 · see citing works
Lona‐Durazo, F., Hernandez‐Pacheco, N., Fan, S., Zhang, T., Choi, J., Kovacs, M. A., Loftus, S. K., Le, P., Edwards, M., Fortes‐Lima, C., et al. (2019) · BMC Genetics · doi:10.1186/s12863-019-0765-5 · Cited by 53 · see citing works
The Evolutionary History of Human Skin Pigmentation
Rocha, J. (2019) · Journal of Molecular Evolution · doi:10.1007/s00239-019-09902-7 · Cited by 50 · see citing works
Edwards, M., Cha, D., Krithika, S., Johnson, M., Cook, G. R., & Parra, E. J. (2015) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12435 · Cited by 47 · see citing works
Pietroni, C., Andersen, J. D., Johansen, P., Andersen, M. M., Harder, S., Paulsen, R. R., Børsting, C., & Morling, N. (2014) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2014.02.002 · Cited by 49 · see citing works
- Authors
- Eiberg, H., Troelsen, J., Nielsen, M., Mikkelsen, A., Mengel-From, J., Kjaer, K. W., & Hansen, L.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Eiberg, Hans
- Venue
- Human Genetics
- Published
- 2008-01-03
- Volume
- 123
- Issue
- 2
- Pages
- 177-187
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- OpenAlex
- W2103578460
- Cited by
- 346
- References
- 30
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 12 · 2023: 18 · 2022: 18 · 2021: 18 · 2020: 23 · 2019: 17 · 2018: 24 · 2017: 17 · 2016: 20 · 2015: 21 · 2014: 30 · 2013: 18 · 2012: 23
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- HERC2, OCA2, founder mutation, regulatory elements, single nucleotide polymorphisms, haplotypes, eye color inheritance, hair color, conserved sequences
- MeSH terms
- Adult, Alleles, Cells, Cultured, Chromosomes, Human, Pair 15, Denmark, Eye Color, Female, Gene Expression Regulation, Genotype, Hair Color, Haplotypes, Humans, Genetic Linkage, Lod Score, Luciferases, Male, Mutation, Pedigree, Surveys and Questionnaires, Regulatory Sequences, Nucleic Acid, Founder Effect, Polymorphism, Single Nucleotide, Guanine Nucleotide Exchange Factors, Membrane Transport Proteins, Ubiquitin-Protein Ligases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
