Promoter polymorphisms in the MATP(SLC45A2) gene are associated with normal human skin color variation
Abstract
Human pigmentation is a complex physical trait in which the membrane-associated transporter protein (MATP) plays an important role as it is involved in intracellular processing and trafficking of melanosomal proteins. Recently, pathogenic mutations in MATP have been shown to cause oculocutaneous albinism type 4, while other polymorphisms are known to have a role in normal pigmentation variation. We previously reported significant associations of two coding region polymorphisms with hair, skin, and eye color in Caucasians. Here we characterize the promoter region of MATP identifying two new transcription start sites and a novel duplication (c.-1176_-1174dupAAT). A total of 700 individuals from five different population groups (529 Caucasians, 38 Asians, 46 African Americans, 47 Australian Aborigines, and 40 Spanish Basques) were genotyped for known promoter polymorphisms c.-1721C>G (rs13289) and c.-1169G>A (rs6867641), as well as c.-1176_-1174dupAAT. Allele frequencies of all three polymorphisms were significantly different between population groups. In Caucasians, the -1721G, +dup, and -1169A alleles were significantly associated with olive skin color. The three promoter polymorphisms were found to be in linkage disequilibrium with each other but not with the two previously reported coding region polymorphisms. Functional analyses in a melanoma cell line showed that the promoter haplotype -1721G, +dup, -1169A significantly decreased MATP transcription. This report provides further evidence for the involvement of MATP in normal pigmentation variation by identifying associations between MATP alleles and skin color variation in Caucasians and demonstrating a functional significance of these polymorphisms.
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Two functional promoter variants and another nonsynonymous polymorphism in SLC45A2, rs26722 (p.E272K), have also been significantly associated with subjectively measured skin color in a population of European ancestry.
“For example, two functional promoter variants and another nonsynonymous polymorphism in SLC45A2, rs26722 (p.E272K), have also been significantly associated with subjectively measured skin color in a population of European ancestry.20”
From A Genomewide Association Study of Skin Pigmentation in a South Asian Population (2007) · cites this paper as [20]
A 3 bp duplication polymorphism within the MATP promoter was recently reported to be associated with normal variation of human skin color.
“A 3 bp duplication polymorphism within the MATP promoter was recently reported, which was associated with normal variation of human skin color (Graf et al., 2007).”
From Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci (2009) · cites this paper as Graf et al., 2007
Altered MITF-mediated MATP promoter transactivation by the reported polymorphisms is not responsible for the differences in endogenous MATP mRNA levels observed in our melanocyte cultures.
“Thus, altered MITF-mediated MATP promoter transactivation by the reported polymorphisms (Graf et al., 2007) seems not to be responsible for the differences in endogenous MATP mRNA levels observed in our melanocyte cultures.”
From Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci (2009) · cites this paper as Graf et al., 2007
A 3 bp indel polymorphism in the MATP promoter, with the absence of the 3 bp, is associated with lighter pigmentation.
“One of these included a 3 bp indel polymorphism, with the absence of the 3 bp associated with lighter pigmentation.”
From Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci (2009) · cites this paper as Graf et al., 2007
SLC45A2/MATP gene promoter polymorphisms are associated with skin color variation within European populations.
“SLC45A2/MATP gene promoter polymorphisms have recently been associated with skin color variation within European populations (Graf et al., 2007).”
From Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci (2009) · cites this paper as Graf et al., 2007
Cites
Valverde, P., Healy, E., Jackson, I., Rees, J. L., & Thody, A. J. (1995) · Nature Genetics · doi:10.1038/ng1195-328 · Cited by 999 · see citing works
Newton, J. M., Cohen-Barak, O., Hagiwara, N., Gardner, J. M., Davisson, M. T., King, R. A., & Brilliant, M. H. (2001) · The American Journal of Human Genetics · doi:10.1086/324340 · Cited by 355 · see citing works
Characterization of Melanocyte Stimulating Hormone Receptor Variant Alleles in Twins with Red Hair
Box, N. F., Wyeth, J. R., O'Gorman, L. E., Martin, N. G., & Sturm, R. A. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.11.1891 · Cited by 338 · see citing works
Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation
Flanagan, N. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.17.2531 · Cited by 276 · see citing works
Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka
Fukamachi, S., Shimada, A., & Shima, A. (2001) · Nature Genetics · doi:10.1038/ng584 · Cited by 245 · see citing works
Graf, J., Hodgson, R., & van Daal, A. (2005) · Human Mutation · doi:10.1002/humu.20143 · Cited by 221 · see citing works
A Polymorphism in the Agouti Signaling Protein Gene Is Associated with Human Pigmentation
Kanetsky, P. A., Swoyer, J., Panossian, S., Holmes, R., Guerry, D., & Rebbeck, T. R. (2002) · The American Journal of Human Genetics · doi:10.1086/339076 · Cited by 183 · see citing works
Oculocutaneous Albinism Type 4 Is One of the Most Common Types of Albinism in Japan
Inagaki, K., Suzuki, T., Shimizu, H., Ishii, N., Umezawa, Y., Tada, J., Kikuchi, N., Takata, M., Takamori, K., Kishibe, M., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/382195 · Cited by 165 · see citing works
Costin, G., Valencia, J. C., Vieira, W. D., Lamoreux, M. L., & Hearing, V. J. (2003) · Journal of Cell Science · doi:10.1242/jcs.00598 · Cited by 164 · 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
A mutation in the MATP gene causes the cream coat colour in the horse
Mariat, D., Taourit, S., & Guérin, G. (2003) · Genetics Selection Evolution · doi:10.1186/1297-9686-35-1-119 · Cited by 142 · see citing works
Bonilla, C., Boxill, L.-A., Donald, S. A. M., Williams, T., Sylvester, N., Parra, E. J., Dios, S., Norton, H. L., Shriver, M. D., & Kittles, R. A. (2005) · Human Genetics · doi:10.1007/s00439-004-1251-2 · Cited by 138 · see citing works
LDA—a java-based linkage disequilibrium analyzer
Ding, K., Zhou, K., He, F., & Shen, Y. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg276 · Cited by 134 · see citing works
Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2
Soejima, M., & Koda, Y. (2006) · International Journal of Legal Medicine · doi:10.1007/s00414-006-0112-z · Cited by 128 · see citing works
Genetic Association and Cellular Function of MC1R Variant Alleles in Human Pigmentation
Sturm, R. A., Duffy, D. L., Box, N. F., Newton, R. A., SHEPHERD, A. G., CHEN, W., Marks, L. H., Leonard, J. H., & Martin, N. G. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03199.x · Cited by 128 · see citing works
Identification of Aim-1 as the underwhiteMouse Mutant and Its Transcriptional Regulation by MITF
Du, J., & Fisher, D. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110229200 · Cited by 105 · see citing works
Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4
Rundshagen, U., Zühlke, C., Opitz, S., SCHWINGER, E., & Käsmann‐Kellner, B. (2004) · Human Mutation · doi:10.1002/humu.10311 · Cited by 96 · 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
Evidence for recent positive selection at the human AIM1 locus in a European population
Soejima, M., Tachida, H., Ishida, T., Sano, A., & Koda, Y. (2006) · Molecular Biology and Evolution · doi:10.1093/molbev/msj018 · Cited by 84 · see citing works
Nakayama, K., Fukamachi, S., Kimura, H., Koda, Y., Soemantri, A., & Ishida, T. (2002) · Journal of Human Genetics · doi:10.1007/s100380200007 · Cited by 66 · see citing works
Harada, M., Li, Y. F., El‐Gamil, M., Rosenberg, S. A., & Robbins, P. F. (2001) · PubMed · Cited by 62 · see citing works
A Polymorphism Study of the Human Agouti Gene and its Association with MC1R
Voisey, J., Box, N. F., & van Daal, A. (2001) · Pigment Cell Research · doi:10.1034/j.1600-0749.2001.140406.x · Cited by 58 · see citing works
Coussens, A. K., & van Daal, A. (2005) · Genomics · doi:10.1016/j.ygeno.2005.02.002 · Cited by 50 · see citing works
Inagaki, K., Suzuki, T., Ito, S., Suzuki, N., Adachi, K., Okuyama, T., Nakata, Y., Shimizu, H., Matsuura, H., Oono, T., et al. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2006.00332.x · Cited by 46 · see citing works
A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA
Voisey, J., Gómez‐Cabrera, M. C., Smit, D. J., Leonard, J. H., Sturm, R. A., & van Daal, A. (2006) · Pigment Cell Research · doi:10.1111/j.1600-0749.2006.00301.x · Cited by 40 · see citing works
MATP polymorphisms in Germans and Japanese: the L374F mutation as a population marker for Caucasoids
Yuasa, I., Umetsu, K., Watanabe, G., Nakamura, H., Endoh, M., & Irizawa, Y. (2004) · International Journal of Legal Medicine · doi:10.1007/s00414-004-0490-z · Cited by 35 · see citing works
Brief communication. A new allelic series for the underwhite gene on mouse chromosome 15
Sweet, H. O., Brilliant, M., Cook, S., Johnson, K., & Davisson, M. (1998) · Journal of Heredity · doi:10.1093/jhered/89.6.546 · Cited by 35 · see citing works
A Korean case of oculocutaneous albinism type IV caused by a D157N mutation in theMATPgene
Suzuki, T., Inagaki, K., Fukai, K., Obana, A., Lee, S., & Tomita, Y. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06403.x · Cited by 33 · see citing works
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Han, J., Kraft, P., Nan, H., Guo, Q., Chen, C., Qureshi, A., Hankinson, S. E., Hu, F. B., Duffy, D. L., Zhao, Z. Z., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000074 · Cited by 499 · see citing works
“Three SNPs in the MATP gene have been associated with human pigmentation: rs16891982 (Phe374Leu), rs26722 (Glu272Lys), and rs13289 C/G (-1721 in the promoter region) [16,17].”
BackgroundChaitanya, 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
A Genomewide Association Study of Skin Pigmentation in a South Asian Population
Stokowski, R. P., Pant, P. V. K., Dadd, T., Fereday, A., Hinds, D. A., Jarman, C., Filsell, W., Ginger, R. S., Green, M. R., van der Ouderaa, F. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/522235 · Cited by 315 · see citing works
“E272K), have also been significantly associated with subjectively measured skin color in a population of European ancestry.(20) Whereas the promoter variants in SLC45A2 were not included in our study, rs26722 was assayed in the present study but showed weaker evidence of association with skin-reflectance measurements…”
ResultForensically Relevant SNP Classes
Budowle, B., & van Daal, A. (2008) · BioTechniques · doi:10.2144/000112806 · Cited by 298 · see citing works
“Other SNPs in the promoter region of this gene, which are not in linkage disequilibrium with the F374L polymorphism, are significantly associated with olive skin color (63).”
BackgroundKayser, M., & Schneider, P. M. (2009) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2009.01.012 · Cited by 276 · see citing works
Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians
Nan, H., Kraft, P., Hunter, D. J., & Han, J. (2009) · International Journal of Cancer · doi:10.1002/ijc.24327 · Cited by 205 · see citing works
“For the promoter polymorphism SLC45A2-1721 C>G, we did not detect any significant associations with pigmentary traits, while a previous study reported an association between this SNP and olive skin color.(45)”
ResultGenetics 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
A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes
Dessinioti, C., Stratigos, A., Rigopoulos, D., & Katsambas, A. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00896.x · Cited by 164 · 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
Darwinian and demographic forces affecting human protein coding genesPreprint
Nielsen, R., Hubisz, M. J., Hellmann, I., Torgerson, D. G., Andrés, A. M., Albrechtsen, A., Gutenkunst, R. N., Adams, M. D., Cargill, M., Boyko, A. R., et al. (2009) · Genome Research · doi:10.1101/gr.088336.108 · Cited by 149 · see citing works
“Strikingly, the second most significant gene is SLC45A2, which has previously been shown to account for part of the variation in human skin color (Graf et al. 2005, 2007).”
Dooley, C. M., Schwarz, H., Mueller, K. P., Mongera, A., Konantz, M., Neuhauss, S. C. F., Nüsslein‐Volhard, C., & Geisler, R. (2013) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12053 · Cited by 140 · see citing works
“Polymorphisms in the SLC45A2 locus had previously been noted to be in linkage disequilibrium when compared between Asian, African, and European populations (Graf et al., 2005, 2007).”
ResultGenome-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
“Three SNPs in the MATP gene have been associated with human pigmentation: rs16891982 (Phe374Leu), rs26722 (Glu272Lys), and rs13289 C/G ( 1721 in the promoter region) (Graf et al., 2005, 2007).”
Cook, A. L., Chen, W., Thurber, A. E., Smit, D. J., Smith, A. G., Bladen, T. G., Brown, D. L., Duffy, D. L., Pastorino, L., Bianchi-Scarra, G., et al. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.211 · Cited by 116 · see citing works
“Thus, altered MITF-mediated MATP promoter transactivation by the reported polymorphisms (Graf et al., 2007) seems not to be responsible for the differences in endogenous MATP mRNA levels observed in our melanocyte cultures.”
BackgroundInfluentialDevelopment 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
Kopp, A. (2009) · Evolution · doi:10.1111/j.1558-5646.2009.00761.x · Cited by 100 · see citing works
“In humans, for example, noncoding variation at the Aim-1 enzyme locus is associated with natural skin color variation (Graf et al. 2007).”
BackgroundRooryck, C., Morice‐Picard, F., Elcioglu, N. H., Lacombe, D., Taı̈eb, A., & Arveiler, B. (2008) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2008.00496.x · Cited by 96 · see citing works
“Finally, patient 030878 carried a missense mutation, and a new variant in the promoter of SLC45A2, a region that was functionally characterized by (Graf et al., 2007).”
BackgroundAssociation 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
“(Graf et al. 2007).”
BackgroundThe 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
“promoter region have also been implicated in natural skin and eye pigmentation variation (Graf et al., 2007; Mengel-From et al., 2010; Sturm and Larsson, 2009).”
BackgroundVariants 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
“However, promoter polymorphisms in the SLC45A2 gene have also recently been shown to be associated with normal human skin color variation [Graf et al., 2007], and it is possible that other SLC45A2 variants may also influence melanoma risk.”
BackgroundDetecting the Genetic Signature of Natural Selection in Human Populations: Models, Methods, and Data
Hancock, A. M., & Rienzo, A. D. (2008) · Annual Review of Anthropology · doi:10.1146/annurev.anthro.37.081407.085141 · Cited by 60 · see citing works
The SLC45 gene family of putative sugar transporters
Vitavska, O., & Wieczorek, H. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.05.014 · Cited by 53 · see citing works
MITF-M regulates melanogenesis in mouse melanocytes
Chen, T., Zhao, B., Liu, Y., Wang, R., Yang, Y., Yang, L., & Dong, C. (2018) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2018.02.008 · Cited by 51 · see citing works
Rapid inexpensive genome-wide association using pooled whole bloodPreprint
Craig, J. E., Hewitt, A. W., McMellon, A. E., Henders, A. K., Ma, L., Wallace, L. M., Sharma, S., Burdon, K. P., Visscher, P. M., Montgomery, G. W., et al. (2009) · Genome Research · doi:10.1101/gr.094680.109 · Cited by 49 · see citing works
“Multiple hits were also found in other known pigmentation genes in the top 1000 associated SNPs: TYR, TYRP1 and top 10,000: SLC24A4, SLC24A5 (see Supplemental Table S1; Graf et al. 2007; Stokowski et al. 2007; Sulem et al. 2007).”
BackgroundBartölke, R., Heinisch, J. J., Wieczorek, H., & Vitavska, O. (2014) · Biochemical Journal · doi:10.1042/bj20140572 · Cited by 44 · see citing works
Canine coat pigmentation genetics: a review
Brancalion, L., Haase, B., & Wade, C. M. (2021) · Animal Genetics · doi:10.1111/age.13154 · Cited by 42 · see citing works
A Partial Gene Deletion of SLC45A2 Causes Oculocutaneous Albinism in Doberman Pinscher Dogs
Winkler, P. A., Gornik, K. R., Ramsey, D., Dubielzig, R., Venta, P., Petersen-Jones, S., & Bartoe, J. T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092127 · Cited by 36 · see citing works
“Sequence variations in the promoter region of SLC45A2 are associated with the historical variation in normal skin pigment between human populations living in northern versus southern regions of the world [36].”
BackgroundHeritability and Genome-Wide Association Studies for Hair Color in a Dutch Twin Family Based Sample
Lin, B. D., Mbarek, H., Willemsen, G. A. H. M., Dolan, C. V., Fedko, I. O., Abdellaoui, A., de Geus, E. J. C., Boomsma, D. I., & Hottenga, J. (2015) · Genes · doi:10.3390/genes6030559 · Cited by 38 · see citing works
“Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color [35,36].”
BackgroundFracasso, N. C. A., de Andrade, E. S., Wiezel, C. E. V., Andrade, C. C. F., Zanão, L. R., da Silva, M. S., Marano, L. A., Donadi, E. A., Castelli, E. C., Simões, A. L., et al. (2017) · Legal Medicine · doi:10.1016/j.legalmed.2016.12.013 · Cited by 36 · see citing works
Chapter 4 The Melanocortin‐1 Receptor Gene Polymorphism and Association with Human Skin Cancer
Beaumont, K. A., Liu, Y. Y., & Sturm, R. A. (2009) · Progress in molecular biology and translational science · doi:10.1016/s1877-1173(09)88004-6 · Cited by 35 · see citing works
Rescue From Oculocutaneous Albinism Type 4 Using Medaka slc45a2 cDNA Driven by Its Own Promoter
Fukamachi, S., Kinoshita, M., Tsujimura, T., Shimada, A., Oda, S., Shima, A., Meyer, A., Kawamura, S., & Mitani, H. (2008) · Genetics · doi:10.1534/genetics.107.073387 · Cited by 27 · see citing works
“…of human SLC45A2 are also related to population differences in human skin color (Nakayama et al. 2002; Soejima et al. 2006; Yuasa et al. 2006; Graf et al. 2007). slc45a2 mRNA is expressed in melanocyte/ melanophore precursors during embryonic development (Fukamachi et al. 2001; Baxter and…”
BackgroundInfluentialIbarrola‐Villava, M., Fernández, L. P., Alonso, S., Boyano, M. D., Peña-Chilet, M., Pita, G., Aviles, J. A., Mayor, M., Gómez‐Fernández, C., Casado, B., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019271 · Cited by 26 · see citing works
“Other variants located on the promoter and in exonic sequences on the SLC45A2 gene have been shown to be significantly associated with dark hair, skin, and eye pigmentation in Caucasian populations [15,23,28,36].”
BackgroundAdaptive potential of genomic structural variation in human and mammalian evolution
Radke, D. W., & Lee, C. (2015) · Briefings in Functional Genomics · doi:10.1093/bfgp/elv019 · Cited by 25 · see citing works
“Olive color skin Human Duplication, partial Promoter region of MATP Graf (2007) [88]”
BackgroundDevelopment of Lentigines in German and Japanese Women Correlates with Variants in the SLC45A2 Gene
Vierkötter, A., Krämer, U., Sugiri, D., Morita, A., Yamamoto, A., Kaneko, N., Matsui, M. S., & Krutmann, J. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.350 · Cited by 24 · see citing works
Skin colour: A window into human phenotypic evolution and environmental adaptation
Liu, J., Bitsue, H. K., & Yang, Z. (2024) · Molecular Ecology · doi:10.1111/mec.17369 · Cited by 25 · see citing works
Genetic basis of oculocutaneous albinism
Rooryck, C., Morice, F., Lacombe, D., Taı̈eb, A., & Arveiler, B. (2009) · Expert Review of Dermatology · doi:10.1586/edm.09.53 · Cited by 20 · see citing works
Cransberg, R., & Munyard, K. (2010) · Small Ruminant Research · doi:10.1016/j.smallrumres.2010.10.004 · Cited by 15 · see citing works
“The matp gene promoter has also been described, with variants being associated with normal human skin colour variation (Graf et al., 2007).”
BackgroundGenetic variants associated with skin photosensitivity in a southern European population from Spain
Hernando, B., Sanz‐Page, E., Pitarch, G., Mahiques, L., Valcuende, F., & Martínez‐Cadenas, C. (2018) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/phpp.12412 · Cited by 14 · see citing works
The color of normal: How a Eurocentric focus erases pigmentation complexity
Norton, H. (2020) · American Journal of Human Biology · doi:10.1002/ajhb.23554 · Cited by 14 · see citing works
Association of common genetic variants with human skin color variation in Indian populations
Sarkar, A., & Nandineni, M. R. (2017) · American Journal of Human Biology · doi:10.1002/ajhb.23068 · Cited by 14 · see citing works
“rs13289 5 33986304 C/G SLC45A2 3 prime UTR variant (Graf et al., 2007)”
Choquet, H., Jiang, C., Yin, J., Kim, Y., Hoffmann, T. J., Aslibekyan, S. W., Auton, A., Babalola, E., Bell, R. K., Bielenberg, J., et al. (2024) · Communications Biology · doi:10.1038/s42003-023-05753-7 · Cited by 12 · see citing works
Distribution and expression of SLC45A2 in the skin of sheep with different coat colors
Wang, H., Xue, L., Li, Y., Zhao, B., Chen, T., Liu, Y., Chang, L., & Wang, J. (2016) · Folia Histochemica et Cytobiologica · doi:10.5603/fhc.a2016.0015 · Cited by 14 · see citing works
“SLC45A2 expression may also be affected by polymorphisms in the MITF promoter [31].”
BackgroundWu, H., Chen, K.-S., Huang, Y.-S., Hsieh, H. J., & Tsai, H. (2023) · BMC Genomics · doi:10.1186/s12864-022-09091-6 · Cited by 13 · see citing works
Reinders, A., & Ward, J. M. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3462 · Cited by 13 · see citing works
“In accordance with this, mutations in SLC45A2 that lower transcription result in a reduction in pigmentation (27).”
BackgroundA 4‐bp deletion promoter variant (rs984225803) is associated with mild OCA 4 among Japanese patients
Okamura, K., Hayashi, M., Nakajima, O., Kono, M., Abe, Y., Hozumi, Y., & Suzuki, T. (2018) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12727 · Cited by 13 · see citing works
“Functional analyses in a melanoma cell line showed that the promoter haplotype –1721G, +dup, –1169A significantly decreased SLC45A2 transcription and that this haplotype was significantly associated with olive (darker) skin color in people of European descent (Graf et al., 2007).”
BackgroundRibero, S., Carrera, C., Tell‐Martí, G., Pastorino, C., Bádenas, C., García‐Herrera, A., Malvehy, J., & Puig, S. (2017) · British Journal of Dermatology · doi:10.1111/bjd.15687 · Cited by 11 · see citing works
Inheritance of white colour in Alpacas: Identifying the genes involved
Munyard, K. (2013) · eSpace (Curtin University) · Cited by 11 · see citing works
Zuo, Z., Yu, Y., Ren, B., Liu, S., Nelson, J. B., Wang, Z., Tao, J., Pradhan‐Sundd, T., Bhargava, R., Michalopoulos, G. K., et al. (2021) · Hepatology Communications · doi:10.1002/hep4.1724 · Cited by 10 · see citing works
Jablonski, N. G. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511781193.016 · Cited by 9 · see citing works
Zhang, C., Ren, Z., & Gong, Z. (2023) · Marine Biotechnology · doi:10.1007/s10126-023-10204-9 · Cited by 7 · see citing works
The genetic basis of human pigmentation
van Daal, A. (2008) · Forensic science international. Genetics supplement series · doi:10.1016/j.fsigss.2007.10.011 · Cited by 7 · see citing works
Andersen, J. D., Meyer, O. S., Simão, F., Jannuzzi, J., de Carvalho, E. F., Andersen, M. M., Pereira, V., Børsting, C., Morling, N., & Gusmão, L. (2020) · International Journal of Legal Medicine · doi:10.1007/s00414-020-02307-y · Cited by 7 · see citing works
“The SNP loci were found in pigmentary genes, including UGT1A [19], SLC45A2 [9, 20, 21], IRF4 [22], EGFR [23], TYRP1 [24], BNC2 [25], TPCN2 [24], TYR [14, 26], GRM5 [27], KITLG [10], DCT [28], SLC24A4 [26], OCA2 [6, 7, 29, 30], HERC2 [6], APBA2 [31], SLC24A5 [31, 32], DEF8 [14], MFSD12 [30], ASIP [15, 24, 33], RALY [14…”
InfluentialBâlteanu, V. A., Cardoso, T. F., Amills, M., Luigi-Sierra, M., Egerszegi, I., Anton, I., & Zsolnai, A. (2020) · Animal Genetics · doi:10.1111/age.13031 · Cited by 7 · see citing works
Evolution of Skin Pigmentation Differences in Humans
López, S., & Alonso, S. (2014) · Wiley eBooks · doi:10.1002/9780470015902.a0021001.pub2 · Cited by 6 · see citing works
Is it possible to use Forensic DNA phenotyping in Brazilian population?
Fridman, C., Cardena, M. M. S. G., Lima, F. D. A., & Gonçalves, F. D. T. (2015) · Forensic science international. Genetics supplement series · doi:10.1016/j.fsigss.2015.09.150 · Cited by 4 · see citing works
“SLC45A2 is a gene known for its rule in human pigmentation traits [1], located on the short arm of chromosome 5 that encodes MATP (membrane-associated transporter protein), which is a transporter that mediates melanin synthesis, since it is responsible to conduct the flow of melanosomal proteins and ions to the melano…”
BackgroundForensic DNA Phenotyping: starting point to prediction model in Pernambuco population, Brazil
de Souza, J. M., Bastos, M. L., Silva, B. D. O., de Lima, K. G. G., de Albuquerque, G. D., de Oliveira, R. S., de Lima, L. P. O., Dellalibera, E., Lins, A. J. D. C. C., & Muniz, M. T. C. (2021) · Research, Society and Development · doi:10.33448/rsd-v10i13.20955 · Cited by 2 · see citing works
“…membrane, its function is linked to the traffic and tyrosinase processing to maintain the melanosome, as well as its pH. (Bin et al., 2015; Graf et al., 2007; J Park, AH Talukder, 1 SA Lim, 2 K Kim, 1 K Pan, 1 B Melendez, 1 SD Bradley, 1 KR Jackson, 1 JS Khalili, 1 J Wang, 1 C Creasy, 1…”
BackgroundEvaluation of the classification method using ancestry SNP markers for ethnic group
Lee, H., Hong, S. P., Lee, S. D., Rhee, H. S., Lee, J., Jeong, S. J., & Lee, J. W. (2019) · Communications for Statistical Applications and Methods · doi:10.29220/csam.2019.26.1.001 · Cited by 4 · see citing works
“…important role as it is involved in intracellular processing and trafficking of melanosomal proteins, and duplication (1176–1174 dupAAT) of promoter and polymorphisms of rs6867641 and rs13289 are known to have significantly different frequencies between population groups (Graf et al., 2005, 2007).”
BackgroundDing, C., Ma, J., Yan, H., Meng, Y., Qi, X., Qu, K., Li, F., Zhang, J., Zhuzha, B., Quji, S., et al. (2022) · Gene · doi:10.1016/j.gene.2022.146643 · Cited by 3 · see citing works
DNA Polymorphisms: What They Are and Their Role in Human Pigmentation
Kosmadaki, M., Stratigos, A., Antoniou, C., & Katsambas, A. (2009) · Actas Dermo-Sifiliográficas · doi:10.1016/s0001-7310(09)73383-6 · Cited by 2 · see citing works
“The role of other polymorphisms in the promoter region of the SLC45A2 gene, reported to be involved in normal variation of human pigmentation 19 , has not been verified in studies with larger samples 20 .”
Veltre, V., Angelis, F. D., Biondi, G., & Rickards, O. (2019) · Forensic science international. Genetics supplement series · doi:10.1016/j.fsigss.2019.09.067 · Cited by 2 · see citing works
Davies, K. T. J., Drinkwater, R., Dávalos, L. M., Nesi, N., Bertelsen, M. F., & Rossiter, S. J. (2025) · Journal of Heredity · doi:10.1093/jhered/esaf070 · Cited by 1 · see citing works
Common Ancestry of the Id Locus: Chromosomal Rearrangement and Polygenic Possibilities
Sharma, A. K., & Vijay, N. (2025) · Journal of Molecular Evolution · doi:10.1007/s00239-025-10233-z · Cited by 1 · see citing works
“For instance, in humans, a SNP in the promoter of the SLC45A2 gene has been linked to variations in skin color (Graf et al. 2007).”
Phenotypic and Genotypic Variation
Leonard, W. R., & Katzmarzyk, P. T. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511781193.013 · Cited by 1 · see citing works
Evolution of Skin Pigmentation Differences in Humans
Norton, H. L. (2008) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0021001 · Cited by 1 · see citing works
The Postracial Imagination: Gattaca 's Imperfect Science
Banner, O. (2011) · Discourse · doi:10.1353/dis.2011.a474425 · Cited by 1 · see citing works
Pigmentation and the cutaneous response to ultraviolet radiation
Wong, T. H. (2009) · ERA
Sims, L. M., & Ballantyne, J. (2007) · Legal Medicine · doi:10.1016/j.legalmed.2007.06.004
“The additional use of other non-golden pigmentation gene SNPs may serve to increase the resolution of the system in the future [17,24–32].”
Naidu, A. G. (2009) · University of the Western Cape Electronic Theses and Dissertations Repository (University of the Western Cape)
Singh, N. B. (2015) · Journal of Institute of Science and Technology · doi:10.3126/jist.v20i2.13959
“For the first time, this polymorphism was used in our laboratory to investigate the genetic variation among the representatives of major human populations with varying degrees of skin pigmentations (Nakayama et al. 2002, Stokowski et al. 2007, Graf et al. 2007).”
BackgroundMethodSeeing in Color: Inclusion and Characterization of Hereditary Eye Disease in African Americans
Owete, A. C., Ionin, R., Huryn, L. A., Cukras, C. A., Blain, D., Agather, A. R., Hufnagel, R. B., Brooks, B. P., Nwanyanwu, K. H., & Zein, W. M. (2024) · Translational Vision Science & Technology · doi:10.1167/tvst.13.9.4
Forensic DNA phenotyping; Current updates and future prospects
Abbas, A., Hussain, S., Saleem, M., Hussain, M., & Saleem, T. (2025) · Journal of Interdisciplinary Research in Allied Health and Pharmacy · doi:10.65406/3j3fh06323 · Cited by 1 · see citing works
- Authors
- Graf, J., Voisey, J., Hughes, I., & van Daal, A.
- Affiliations
- Queensland University of Technology (AU)
- Corresponding author
- Graf, Justin
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2007-07
- Volume
- 28
- Issue
- 7
- Pages
- 710-717
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2020662754
- Cited by
- 72
- References
- 29
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 2 · 2012: 3
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- 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
- MatP, SLC45A2, promoter polymorphism, skin pigmentation, skin color variation, transcription start sites, linkage disequilibrium, allele frequency, promoter haplotypes, Caucasians
- MeSH terms
- Antigens, Neoplasm, Base Sequence, Chromatography, High Pressure Liquid, Haplotypes, Humans, Luciferases, Promoter Regions, Genetic, Skin Pigmentation, Linkage Disequilibrium, Genes, Reporter, DNA Primers, DNA, Complementary, Polymorphism, Single Nucleotide, Membrane Transport Proteins, White People, Cell Line, Tumor
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