pigmented iris genotype

The most common, which the OCA2 gene is named for, is oculocutaneous albinism. Some phenotypes however, are determined by a single gene. Most of the haplotypes were even more dramatically associated with iris colors in a multiracial sample (data not shown), because many of the SNPs comprising them are good AIMs and variants associated with darker iris colors were enriched in those ancestral, The common haplotypes and diplotypes for the 16 iris color genes discussed in the text. The two rounds were necessary due to the fact that many of the genes we queried were members of gene families, the SNPs resided in regions of sequence homology, and our genotyping platform required short (100 bp) amplicons. In the absence of melanin brown pigment, the iris is blue. The pigmented structure inside the eye that surrounds the pupil and gives eyes their color is called the iris. However, it is yet to be completely understood. 1993; Smith et al. In the case of the mutation within HERC2, the expression of the P protein encoded by OCA2 decreases, effectively decreasing its effects in pigmentation. CAS https://doi.org/10.1038/jhg.2010.126, DOI: https://doi.org/10.1038/jhg.2010.126. In other words, the distribution of SNPs among the various gene types was also not random. What is your genotype for this trait? . The gene contains a main coding region for brown eyes (BEY2 15q11-15) and hazel eyes (BEY1).3, 5 Other SNPs result in blue and green eyes. A golden-brown iris indicates the mixture of both eumelanin and pheomelanin (produces the yellow color), and hazel is usually a mixture of brown and green or blue and green, depending on the shade. et al. Although eye color is usually modeled as a simple, Mendelian trait, further research and observation has indicated that eye color does not follow the classical paths of inheritance. The quantity and quality of melanin in the cytoplasm determines the observed color of the eye. The little that isn't absorbed by the iris is reflected back, producing what we see as eye color. All of the major sequences (count 13) for each locus with at least one significantly associated sequence are shown. 1997), and other genes (reviewed by Sturm et al. Slider with three articles shown per slide. Forensic Sci Int: Genet. The sequences we have identified constitute a good first step toward developing a classifier model for the inference of iris colors from DNA, and the nature of some of these as markers of population structure might have implications for the design of other complex trait gene-mapping studies. For example, skin color and height are determined by many genes. Oetting, W. S. & King, R. A. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. That is, the occurrence of an allele for eye pigmentation in a gamete has nobearing on which allele for chin form will occur in that same gamete. This gene is often referred to as the red-headed gene because of its prevalent expression in people with red hair and green eyes.4 Dopachrome tautomerase also contains regions for hazel and green eyes.5 Regions for brown eyes dominate the effects of these genes, though. Following your lab manual and your tutor's instructions fill out this table: Trait Phenotype Possible genotypes Class frequency Pigmented iris Pigment No pigment PP Pp pp Pigmented iris = 79% No pigment= 21% Tongue rolling Yes no RR Rr rr 78% can 22% cannot Bent little finger Yes No BB Bb bb 20% can 80% cannot Widow's peak Yes No WW Ww ww . If you exhibit the dominant phenotype, use a dash to represent the second allele. This same phenomenon is the reason why the pupil appears black. Forensic Sci Int: Genet. We also thank Robert White for his help with sample collection. We identified 5 additional genes (ASIP, MC1R, POMC, and SILV) and one additional region (GSTT2-22q11.23) with haplotype and/or diplotypes, but not individual SNP alleles associated with iris colors. BLAST searches confirmed the specificity of all primers used. Nat Genet. The disorder is characterized by different-colored irises or different colors within the iris. In melanocyte-specific organelles known as melanosomes, two pathways for melanogenesis occur. On the HERC2/OCA2 A/A and A/G genotype background there was an increasing proportion of blue eye colour when carrying the IRF4 T allele (P = 3 10 4) and a higher number of iris pigmented lesions with the IRF4 T/T homozygote (P . The Louisville twin study, Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as OCA3., Characterization of melanocyte stimulating hormone variant alleles in twins with red hair, Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma, Estimation of the heritability of hair and iris color, Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter, Excision of the DBA ecotropic provirus in dilute coat-color revertants of mice occurs by homologous recombination involving the viral LTRs, African origin of an intragenic deletion of the human P gene in tyrosinase positive oculocutaneous albinism, Estimation of carrier frequency of a 2.7 kb deletion allele of the P gene associated with OCA2 in African-Americans, Assignment of genes coding for brown iris colour (BEY2) and brown hair colour (HCL3) on chromosome 15q, Pleiotropic effects of the melanocortin 1 receptor (MC1R) gene on human pigmentation, A classifier for the SNP-based inference of ancestry, The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes, Molecular study of the Prader-Willi syndrome: deletion, RFLP, and phenotype analyses of 50 patients, Individual admixture estimates: disease associations and individual risk of diabetes and gallbladder disease among Mexican-Americans in Starr County, Texas, The color of the human iris: a review of morphologic correlates and of some conditions that affect iridial pigmentation, A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse, A second tyrosinase-related protein, TRP-2, maps to and is mutated at the mouse slaty locus, A polymorphism in the Agouti signaling protein gene is associated with human pigmentation, An unusual pigment pattern in type I oculocutaneous albinism (OCA) resulting from a temperature-sensitive enzyme. Further, certain of our results support the previous literature. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. The change of this base from a C to a T causes a change from brown eyes to non-brown eyes (usually blue). .. Chintamaneni C D, Ramsay M, Colman M-A, Fox M F, Pickard R T et al. Am J Hum Genet 80, 241252 (2007). Half of the associated SNPs were located on chromosome 15, which corresponds with results that others have previously obtained from linkage analysis. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. E_ Free earlobes. The front layer of the iris (called the stroma) can make eyes appear brown, blue or green. Allele Variations in OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma. Teaching the genetics of eye colour & colour vision. In addition, for 103 of the subjects, iris colors were reported using a number from 1 to 11 as well, where 1 is the darkest brown/black and 11 is the lightest blue, identified using a color placard. Mutations in the pigmentation genes are the primary cause of oculocutaneous albinism so it was natural to expect that common variations in their sequences might explain some of the variance in natural iris colors, and this is in fact what we observed. Phakomatoses. Genetics 165, 20712083 (2003). Lighter shades of brown and gray, a lighter shade of blue, show a mixture of two phenotypes where neither dominates completely. For example, the OCA2 has 200 known candidate SNPs in NCBI's dbSNP, and it is possible that this gene has more to teach us about variable human iris pigmentation than what we have learned from the work presented herein. ), Molecular analysis of type I-A (tyrosine negative) oculocutaneous albinism, Molecular basis of type I (tyrosinase-related) oculocutaneous albinism: mutations and polymorphisms of the human tyrosinase gene, Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism, Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila iris color mutant garnet, P gene as an inherited biomarker of human eye color, Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function, Loss of function mutations of the human melanocortin 1 receptor are common and are associated with red hair, Molecular basis of dark-eyed albinism in the mouse, Skin pigmentation, biogeographical ancestry and admixture mapping, Melanocortin 1 receptor variants in an Irish population, Empirical Bayes adjustments for multiple results in hypothesis-generating or surveillance studies, A new statistical method for haplotype reconstruction from population data, Molecular analysis of two mouse dilute locus deletion mutations: spontaneous dilute lethal-20J and radiation-induced dilute prenatal lethal Aa2 alleles, Human pigmentation genes: identification, structure and consequences of polymorphic variation, Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans, A mutation in Rab27a causes the vesicle transport defects observed in ashen mice, Exact tests for association between alleles at arbitrary numbers of loci, This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, Selection and Geography Shape Male Reproductive Tract Transcriptomes in Drosophila Melanogaster, From Multi-Allele Fish to Non-Standard Environments, How ZFIN Assigns Phenotypes, Human Disease Models, and Gene Expression Annotations to Genes, Genetic association models are robust to common population kinship estimation biases, 101 years ago: Hermann Muller's remarkable insight, https://doi.org/10.1093/genetics/165.4.2071, https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model, Receive exclusive offers and updates from Oxford Academic, Adaptor-related protein complex 3, -1 subunit, Adaptor-related protein complex 3, -1 subunit, Copyright 2023 Genetics Society of America. Rinchik, E. M., Bultman, S. J., Horsthemke, B., Lee, S., Strunk, K. M., Spritz, R. A. et al. Although research on pigment mutants has made clear that a small subset of genes is largely responsible for catastrophic pigmentation defects in mice and humans, it remains unclear whether or how common single-nucleotide polymorphisms (SNPs) in these genes contribute toward (or are linked to) natural variation in human iris color. (2002) recently described two OCA2 coding changes associated with darker iris colors. This provides an explanation why some babies develop their eye color, but skin pigmentation changes constantly throughout life. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. If you have no pigment you have either blue or gray eyes. Genotypes for these 754 candidate SNPs were scored for 851 European-derived individuals of self-reported iris colors (292 blue, 100 green, 186 hazel, and 273 brown). E-mail: Search for other works by this author on: The human homolog of the mouse brown gene maps to the short arm of chromosome 9 and extends the known region of homology with mouse chromosome 4, Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population, Discrete visual defects in pearl mutant mice, Human tyrosinase gene, mapped to chromosome 11 (q14-q21), defines second region of homology with mouse chromosome 7, Iris color changes past early childhood. The promoter region for OCA2 is located within the HERC2 gene. More than likely, their offspring would have blue eyes, but a 25% chance stands that offspring would have brown eyes. Digital quantification of human eye color highlights genetic association of three new loci. In all, 27 SNPs were significantly associated with iris pigmentation using at least one of the four criteria, and we refer to these as marginally associated. Some individuals may express two phenotypesone in each eyeor a complete lack of pigmentation, ocular albinism. 11. 2003). The "P" allele produces the pigment which gives you eye color. .. Frudakis T, Venkateswarlu K, Thomas M J, Gaskin Z, Ginjupalli S et al. Phenotypic Effect. In the presence of cysteine, the reaction will proceed to form pheomelanin. (d) List the possible genotypes of a blue eyed individual lacking a dimpled chin. Aside from HERC2 and OCA2, the other genes involved in melanin production have some regions that correlate to other eye colors.5 MC1R contains regions that increase the probability of obtaining green eyes. P_ Pigmented Iris (Additional genes give specific color, e.g. The iris consists of five cell layers, the anterior border layer, stroma, the sphincter and dilator muscles fibers, and the posterior pigment epithelium ( Figure 1 ), of which the most important for the appearance of eye colour are the anterior layer and its underlying stroma ( Eagle, 1988; Imesch et al., 1996; Wilkerson et al., 1996 ). Indeed, one of those for which the evidence of lack of HWE was the strongest was validated as a legitimate SNP through direct DNA sequencing (data not shown). Redei, G. Encyclopedia of Genetics, Genomics, Proteomics, and Informatics, 3rd edn (Springer, New York City, NY, 2008). 20, 327332 (2004). Most of the SNPs within a gene or region were in LD with others in that gene or region (|D| 0.05); only 32 SNP pairsin the MC1R (1 pair), OCA2 (27 pairs), TYR (2 pairs), and TYRP1 (2 pairs) geneswere found to be in linkage equilibrium (not shown). 1992; Durham-Pierre et al. .. Robbins L S, Nadeau J H, Johnson K R, Kelly M A, Roselli-Rehfuss L et al. A brown-iris locus was localized to an interval containing the OCA2 and MYO5A genes (Eiberg and Mohr 1996), and specific polymorphisms in the MC1R gene have been shown to be associated with red hair and blue iris color in relatively isolated populations (Robbins et al. Peripheral scalloping of the posterior pigmented iris layer. For these subjects, we obtained digital photographs of the right iris, where subjects peered into a box at one end at the camera at the other end to standardize lighting conditions and distance and from which a judge assigned the sample to a color group. Specimens for genotyping were of self-reported European descent, of different age, sex, hair, iris, and skin shades and they were collected using informed consent guidelines under Investigational Review Board guidance. Incomplete dominance shows in individuals with lighter shades of brown and hazel. Google Scholar. (2003) within the context of a software program we developed for this purpose, which will be presented elsewhere (T. Frudakis, Z. Gaskin, M. Thomas, V. Ponnuswamy, K. Venkateswarlu, S. Gunjupulli, C. Bonilla, E. Parra and M. Shriver, personal communication). b) Give the genotype of an individual who is homozygous recessive for brown eye color. 2) although some associations were found within nonpigmentation genes such as CYP2C8 at 10q23, CYP2C9 at 10q24, CYP1B1 at 2p21, and MAOA at Xp11.3. The "P" allele produces the pigment which gives you eye color. .. Kanetsky P, Swoyer J, Panossian S, Holmes R, Guerry D et al. The next steps in eye color research involve hue classification among populations. .. Kwon B S, Chintamaneni C, Kozak C A, Copeland N G, Gilbert D J et al. European J Genet 17, 317 (2009). 1991; Boissy et al. In mice and humans where the P protein is nonfunctional, albinism occurs, indicating its crucial role in pigmentation.13, 14 The gene located 11.7kb from HERC2 requires 345kb, but it requires only 24 exons to produce a 110kDa protein with 838 residues. Most of the SNPs that we identified were on chromosome 15, which Eiberg and Mohr (1996) described from linkage analyses as the primary chromosome for the determination of brownness. As suggested by these authors, the candidate gene within the interval containing this locus (BEY2) is most likely the OCA2 gene, although the MYO5A gene is also present within this interval and, as shown here, associated with iris colors. Also, if an allele does code for brown, the individual will have brown eyes, except for cases where a critical gene is turned off. Number of times the haplotype was observed in our sample of 851. groups of the world that are of darker average iris color (Frudakis et al. Antagonist color refers to the color with which the sequence is negatively associated. Sulem, P., Gudbjartsson, D., Stacey, S., Helgason, A., Rafnar, T., Magnusson, K. P. et al. The most strongly associated of the marginally associated SNPs were from the OCA2, TYRP1, and AIM genes, in order of the strength of association, which is the same order as that provided using the number of marginally associated SNPs, rather than their strength. In studies with HERC2 functions, deletions caused hypopigmentation even though the protein has nothing to do with pigmentation. Kayser, M., Liu, F., Janssens, A. C., Rivadeneira, F., Lao, O., van Duijn, K. et al. When a pigment is deposited in the front layer of the iris, this masks the blue layer to varying degrees. .. Krude H, Biebermann H, Luck W, Horn R, Brabant G et al. Each of these genes is part of the main (TYR) human pigmentation pathway. TYR catalyzes the rate-limiting step of melanin biosynthesis and the degree to which human irises are pigmented correlates well with the amplitude of TYR message levels (Lindsey et al. 2000), and adaptin 3B (AP3B) loci (Ooi et al. TYR, located from 11q14-q21, begins the melanogenesis pathway. The chromosomal distribution of the SNPs that were significantly associated in a marginal sense was found to be independent of the distribution of SNPs actually surveyed, indicating that the associations were not merely a function of SNP sampling and the same was true for the distribution of all the SNPs shown in Table 2 (data not shown). lack pigment in skin (recessive) pigmented iris - pigments (dominant) hides blue/gray color of iris back layer ; attached earlobes - free earlobes dominant over attached earlobes ; hitchhiker's thumb - last joint of thumb bends back over 60 degrees . In addition, the evolutionary and population roles of the different expressions are significant. Because most human traits have complex genetic origins, wherein the whole is often greater than the sum of its parts, innovative genomics-based study designs and analytical methods for screening genetic data in silico that are respectful of genetic complexity are neededfor example, the multifactorial and/or phase-known components of dominance and epistatic genetic variance. The pigment responsible for eye color is called melanin, which also affects skin color. 1991; Chintamaneni et al. To an investigator interested in elucidating a biological mechanism, association due to population structure might not seem to be very satisfying, but when classification is the goal rather than the elucidation of a biological mechanism, it would seem to matter little why a marker is associated with a trait. The P values we obtained suggested that diplotypes explained more iris color variation than did haplotypes or individual SNPs. Further studies of this region and its sequence revealed that a change in one nucleotide, single-nucleotide polymorphism (SNP), regulates the binding site for the transcription of the OCA2 gene, altering its expression.9 The base changes from a thymine to a cytosine. Internet Explorer). Heterochromia, although not viewed as a severe disorder, affects many individuals. _____ Pigmented Iris If you are homozygous for the recessive allele "p", you do not produce pigment in the front layer of your iris. We also identified associations in the ASIP gene, which supports previous work by Kanetsky et al. For example, OCA2, AIM, DCT, and TYRP1 harbored haplotypes both positively associated with blue irises and negatively associated with brown irises (OCA2 haplotypes 1, 37, 38, 42; AIM haplotype 1; DCT haplotype 2; and TYRP1 haplotype 1; Table 3). Already, some researchers have started studying hues and saturations. The second parent has a non-mutated HERC2 allele but does not have the coding for brown eyes in the OCA2 gene. In this pedigree use "A" to represent the dominant allele and "a" for the recessive allele.A An ASIP polymorphism is reported to be associated with both brown iris and hair color (Kanetsky et al. Different SNPs on these two genes were investigated and analyzed for melanoma risk.24, 25. In this case, pleiotropic effects change eye color. An intron in HERC2 contains the promoter region for OCA2, affecting its expression. The possible changes in the DNA sequence are GCT to GTT and GCC to GTC. We also acknowledge previous National Science Foundation support under grant numbers 1246120, 1525057, and 1413739. 1991; Gardner et al. PubMed Central The first step, however, is to define the complement of loci that on a sequence level explain variance in trait value and, of these, those that do so in a marginal or penetrant sense will be the easiest to find. CAS 1994). Place the PTC paper on your tongue for a few seconds. CAS In the traditional view of eye color, it was taught that two blue-eyed individuals could only produce blue-eyed offspring. Lastly, disorders involved in eye color include ocular albinism and heterochromia. Pigmented Iris If you are homozygous for the recessive allele "p", you do not produce pigment in the front layer of your iris. Zaumseger, D., Rothschild, M. & Schneider, P. SNPs for the analysis of human pigmentation genes--A comparative study. However, this result would not have necessarily been obtained were we working with SNPs that were not truly associated with iris colors. Cassidy, S. B. 1998), but mouse studies have suggested that 14 genes preferentially affect pigmentation in vertebrates (reviewed in Sturm et al. Genotyping: For most of the SNPs, a first round of PCR was performed on the samples using the high-fidelity DNA polymerase pfu Turbo and the appropriate resequencing primers. For these genes we performed resequencing and of the genes discussed in this article, 113 SNPs were discovered in CYP1A2 (7 gene regions, 5 amplicons, 10 SNPs found), CYP2C8 (9 gene regions, 8 amplicons, 15 SNPs found), CYP2C9 (9 gene regions, 8 amplicons, 24 SNPs found), OCA2 (16 gene regions, 15 amplicons, 40 SNPs found), TYR (5 gene regions, 5 amplicons, 10 SNPs found), and TYRP1 (7 gene regions, 6 amplicons, 14 SNPs found). Specimens: Specimens for resequencing were obtained from the Coriell Institute in Camden, New Jersey. Clearly work remains to be done, objectifying the collection of iris colors from subjects, enhancing the sample size so that epistatic interactions can be explored, possibly screening other regions of the genome not screened here, and modeling the sequences that we have described to enable classification of iris colors from DNA. (2000). Google Scholar. Eumelanin (brown pigment) is a light-absorbing polymer synthesized in specialized melanocyte lysosomes called melanosomes. Branicki, W., Brudnik, U. MYO5A alleles were not found to be in LD with those of OCA2, suggesting that these results were independently obtained and that Eiberg and Mohr's results may have been a reflection of the activity of two separate genes. This is an example of a hihybrid crosses. One leads to eumelanin, a darker pigment (brown-black), and the other to pheomelanin, a light pigment (red-yellow). 39, 14431452 (2007). A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Although cysteine is not an essential amino acid and its deficiency rarely occurs, the lack of it halts the production of pheomelanin. They help with hormone secretion, which affects the pituitary and can lead to dysfunction of the hypothalamus and other protein complexes. Thank you for visiting nature.com. White, D., Rabago-Smith, M. Genotypephenotype associations and human eye color. As the eye color lightens, less melanin is present in the cells, reflecting more of the visible spectrum. Genetic determinants of hair, eye and skin pigmentation in Europeans. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye Color. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Other genes determine the nature and density of the pigment, giving us brown, hazel, violet, green and other eye colors. Blue is confined mostly to people who originated from Europe.11 Green eyes permeate the lowest amount of the population (excluding the disorders), probably due to the lack of coding for it within the genome. OCA2 ranges from 15q11.2-12 and HERC 2 starts at 15q13. A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. For each gene, we inferred haplotypes and used contingency analyses to determine which haplotypes were statistically associated with iris colors. Eiberg, H., Troelsen, J., Nielsen, M., Mikkelsen, A., Mengel-From, J., Kjaer, K. et al. CAS PubMedGoogle Scholar. (a) List all possible genotypes for an individual with pigmented iris and dimpled chin. However, the results presented herein constitute a good first step toward solving what our results confirm is a very complex genetics problem. a) Give the genotype of an individual, who is homozygous dominant for Brown eye color, where "B" is the letter used to distinguish this trait. .. Steenland K, Bray I, Greenland S, Boffetta P. Strobel M C, Seperack P K, Copeland N G, Jenkins N A. Valverde P, Healy E, Jackson I, Rees J L, Thody A J. Wilson S M, Yip R, Swing D A, OSullivan T N, Zhang Y et al. One SNP has been studied to show a large significance for eye color. For example, unlike human hair color (Sturm et al. ., Oxford University Press is a department of the University of Oxford. .. Lindsey J D, Jones H L, Hewitt E G, Angert M, Weinreb R N. Lyon M F, King T R, Gondo Y, Gardner J M, Nakatsu Y et al. These observations suggest that the genetic determinants for pigmentation in the various tissues are distinct and that these determinants have been subject to a common set of systematic and evolutionary forces that have shaped their distribution in world populations. Although we screened a large number of SNPs, some of the genes harbor a large number of candidate SNPs and we did not test them all. Although our results independently verified findings for OCA2, ASIP, and MC1R, they also show that several other pigmentation genes harbor alleles associated with the natural distribution of iris colors (TYRP1, AIM, MYO5A, and DCT). The process that produces melanin, known as melanogenesis, requires numerous proteins. Article Predicting phenotype from genotype: normal pigmentation. The structure behind our results is unlikely to be of a crude (i.e., continental) nature; although two-thirds of our European-American samples were of significant (4%) BGA admixture, few correlations between structure measured on this level and iris colors were observed in this study. 1997; Lloyd et al. Google Scholar. The solid figures represent albino individuals. No significant SNP associations within the pigmentation genes SILV, MC1R, ASIP, POMC, RAB, or TYR were found, although TYR had one SNP with a P = 0.06. Although the crystal structure has not been published for the P protein coded by OCA2, residue 419 is predicted to face the cytoplasmic portion of the lipid bilayer in one of the several transmembrane domains.14 Therefore, the SNP change that results in R419Q most likely affects the P protein in conformation. pigmented iris genotype On the HERC2/OCA2 A/A and A/G genotype background there was an increasing proportion of blue eye colour when carrying the IRF4 T allele (P = 3 10-4 ) and a higher number of iris pigmented lesions with the IRF4 T/T homozygote (P = 3 10-9 ). Provided by the Springer Nature SharedIt content-sharing initiative, Graefe's Archive for Clinical and Experimental Ophthalmology (2022), Cellular and Molecular Life Sciences (2016), Journal of Human Genetics (J Hum Genet)

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