CAS In addition, the evolutionary and population roles of the different expressions are significant. For some genes, the number of SNPs in the database was low and/or some of the SNPs were strongly associated with iris colors, warranting a deeper investigation. 1999; Flanagan et al. Peripheral scalloping of the posterior pigmented iris layer. 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. (gray/blue). Article 2001), there appears to be only a minor dominance component for mammalian iris color determination (Brauer and Chopra 1978), and minimal correlation exists among skin, hair, and iris color within or between individuals of a given population. At the level of the haplotype, each gene or region had unique numbers and types of associations. At the cellular level, variable iris color in healthy humans is the result of the differential deposition of melanin pigment granules within a fixed number of stromal melanocytes in the iris (Imesch et al. The "P" allele produces the pigment which gives you eye color. PubMed Central The exact nature and density One of these, the Arg305TRP SNP, was one of the 13 OCA2 SNPs that we found to be strongly associated with iris colors using all four of our color criteria, although its association was only the ninth strongest among the OCA2 SNPs that we identified and the eleventh strongest among all of the associated SNPs that we identified. PubMed Central . Accessibility StatementFor more information contact us atinfo@libretexts.orgor check out our status page at https://status.libretexts.org. Although such an error is tolerable for identifying sequences marginally associated with iris colors, the use of the sequences described herein for iris color classification would therefore likely require digitally quantified iris colors (which we have begun to accumulate and will present elsewhere). This page titled 8.2: Human Traits Determined by Single Genes is shared under a CC BY 4.0 license and was authored, remixed, and/or curated by Ellen Genovesi, Laura Blinderman, & Patrick Natale via source content that was edited to the style and standards of the LibreTexts platform; a detailed edit history is available upon request. To take advantage of each of these four methods, we considered all of them when screening SNPs for associations; we calculated the value, chi square, and exact test P values for (a) all four colors, (b) shades, using light (blue and green) vs. dark (hazel and brown), (c) blue vs. brown, and (d) brown vs. not brown (blue, green, and hazel) groupings. The recessive allele (b) encodes blue eyes. Tony Frudakis, Matthew Thomas, Zach Gaskin, K Venkateswarlu, K Suresh Chandra, Siva Ginjupalli, Sitaram Gunturi, Sivamani Natrajan, Viswanathan K Ponnuswamy, K N Ponnuswamy, Sequences Associated With Human Iris Pigmentation, Genetics, Volume 165, Issue 4, 1 December 2003, Pages 20712083, https://doi.org/10.1093/genetics/165.4.2071. . In studies with HERC2 functions, deletions caused hypopigmentation even though the protein has nothing to do with pigmentation. Some individuals may express two phenotypesone in each eyeor a complete lack of pigmentation, ocular albinism. All visible light is absorbed by the retina. In humans, eye color is determined by the amount of light that reflects off the iris, a muscular structure that controls how much light enters the eye. 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. For some, associations with iris colors were found only within the context of diplotypes, but not at the level of the SNPs or the haplotype (i.e., SILV and GSTT2 genes located at 22q11.23). Forensic Sci Int: Genet. Of course, identifying markers in LD with phenotypically active loci (or the phenotypically active loci themselves) would provide for more accurate classification (as well as for a better understanding of biological mechanism), but the hunt for these elusive loci in heterogeneous populations is still impractical because LD extends only for a few kilobases and the economics of genome-wide scans in heterogeneous samples with full LD coverage are out of reach for most labs. 2000). The possible changes in the DNA sequence are GCT to GTT and GCC to GTC. Am J Hum Genet 82, 424431 (2008). Attached earlobes. Petunias with genotype R1R1 are red flowered, R1R2 are pink flowered and R2R2 are white flowered. The traditional view was correct in which an allele that codes for brown is dominant over green or blue, and green takes precedence over blue.2, Melanocytes in the stroma and anterior layers of the eye hold melanin in their cytoplasms. The change of this base from a C to a T causes a change from brown eyes to non-brown eyes (usually blue). With the help of dopachrome tautomerase and TYR-related protein 1, eumelanin, the darker pigment, is synthesized; with cysteine, pheomelanin, a yellow-red pigment, is produced. By analyzing the DNA from a crime scene, the general phenotypic traits of the suspect may be pieced together.21, 22, 23 Tully suggests that it may help eliminate particular groups of suspects in circumstances with few leads. Further, certain of our results support the previous literature. Multiple SNPs were identified on chromosome 10q; the CYP2C8-10p23 region had 1 marginally associated SNP, and the neighboring region, CYP2C9-10p24, also had one. This also explains why deletions within HERC2 would cause a decrease in melanin without interacting with the P protein itself. brown, hazel) P > p. pp. Genotyping was performed for individual DNA specimens using a single base primer extension protocol and an SNPstream 25K/ultra-high throughput (UHT) instrument (Beckman Coulter, Fullerton, CA, and Orchid Biosystems, Princeton, NJ). We thank D. C. Rao, Director of the Division of Biostatistics, Washington University, St. Louis, for help preparing this manuscript; Mark Shriver, Department of Anthropology and Human Genetics at The Pennsylvania State University for his help with the biogeographical ancestry admixture aspect of the project; and Murray Brilliant, professor of Pediatrics and Molecular and Cellular Biology at the University of Arizona for their kind advice and support of our work. . Eumelanin (brown pigment) is a light-absorbing polymer synthesized in specialized melanocyte lysosomes called melanosomes. .. Durham-Pierre D, King R A, Naber J M, Laken S, Brilliant M H. Flanagan N, Healy E, Ray A, Philips S, Todd C et al. Individuals for whom iris color was ambiguous or had changed over the course of life were eliminated from the analysis. .. Copeland N G, Hutchison K W, Jenkins N A. Durham-Pierre D, Gardner J M, Nakatsu Y, King R A, Francke U et al. Asterisks represent P values that remained significant after the correction for multiple tests and P values in italic are those that were statistically significant (P 0.05). Incomplete dominance shows in individuals with lighter shades of brown and hazel. For more extensively admixed individuals, we observed no correlation between higher levels (>33% but <50%) of Native American admixture and iris colors, although there was a weak association between higher levels of East Asian and sub-Saharan African admixture and darker iris colors (data not shown). PubMed In the absence of melanin brown pigment, the iris is blue. Decreased expression of OCA2 affects the pathway for melanosome maturation. Half of the associated SNPs were located on chromosome 15, which corresponds with results that others have previously obtained from linkage analysis. 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). This information revealed more factors for determining eye color in European populations.20 Tully, Valenzuela and Zaumseger suggest using genotype data for forensic analysis. Pigment Cell Res 14, 8693 (2001). Also, if an allele does code for brown, the individual will have brown eyes, except for cases where a critical gene is turned off. 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. However, it is yet to be completely understood. We identified numerous SNPs, haplotypes, and diplotypes (diploid pairs of haplotypes) within the OCA2, MYO5A, TYRP1, AIM, DCT, and TYR genes and the CYP1A2-15q22-ter, CYP1B1-2p21, CYP2C8-10q23, CYP2C9-10q24, and MAOA-Xp11.4 regions as significantly associated with iris colors. 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. During pigment distribution in an infant, a diet low in cysteine or methionine, which it is synthesized from, would likely affect the color of the child's eyes until the amino acid is supplemented. Problems with just HERC2 lead to nerve tissue malfunctioning, small size and semi-sterility or sterility. PTC tasting If you can taste PTC, you have the dominant allele (P). The main pigment in the eye is the dark brown melanin, whilst the scattering of light from the collagen fibres in the sclera make it appear white and the haemoglobin in the blood vessels appears. Here, we present an analysis of iris phenotypes among 16 mouse strains with mutations influencing melanosomes. In this case, pleiotropic effects change eye color. When light passes through a large amount of melanin, most of the visible light is absorbed, and the little that is reflected back appears brown. There are thought to be about 20,000 genes in human DNA. Lighter shades of brown and gray, a lighter shade of blue, show a mixture of two phenotypes where neither dominates completely. We also acknowledge previous National Science Foundation support under grant numbers 1246120, 1525057, and 1413739. We developed a program (T. Frudakis, M. Thomas, Z. Gaskin, K. Venkateswarlu, K. Suresh Chandra, S. Ginjupalli, S. Gunturi, S. Natrajan, V. K. Ponnuswamy and K. N. Ponnuswamy, unpublished results) to design resequencing primers in a manner respectful of homologous sequences in the genome, to ensure that we did not coamplify pseudogenes or amplify from within repeats. 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. 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). Complete the table. 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. Therefore, it seems that our findings indicate that most of the previous results associating pigmentation gene alleles with iris colors, taken independently, represent merely strokes of a larger, more complex portrait. Chi-square P value is shown. Article The pedigree in the accompanying illustration shows the inheritance of albinism, a homozygous recessive condition resulting in a total lack of pigment. In this pedigree use "A" to represent the dominant allele and "a" for the recessive allele.A Digital quantification of human eye color highlights genetic association of three new loci. 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. Red and violet eyes come from a lack of pigment. 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. 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. Transcribed image text: P>p Trait Genotype Phenotypic Effect Relationship P. Pigmented Iris (Additional genes give specific Iris Color color, e.g. CAS In the meantime, to ensure continued support, we are displaying the site without styles All of the major sequences (count 13) for each locus with at least one significantly associated sequence are shown. We focused on human pigmentation and xenobiotic metabolism genes, selected on the basis of their gene identities, not their chromosomal position. 1991; Gardner et al. 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. Therefore, single-nucleotide polymorphisms in either of these two genes have a large role in the eye color of an individual. The solid figures represent albino individuals. 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. .. Lastly, disorders involved in eye color include ocular albinism and heterochromia. Genotype. From the chi-square and adjusted residuals, we found 43 haplotypes for 16 different loci to be either positively (agonist) or negatively (antagonist) associated with iris colors (Table 3). His wife Jenny has free earlobes and . 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. European J Hum Genet 13, 913920 (2005). Pigmented iris: If a person is homozygous recessive for eye color, there is no pigment in the front part of the eyes, and the blue color of the back of the iris shows through, giving blue eyes . An individual with this disorder produces little or no pigment in their ocular melanocytes. Although this could indicate that the SNPs are in LD with other phenotypically active loci, it may also be a reflection that variability in message transcription and/or turnover may explain part of the variability observed in human iris colors. 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. The front layer of the iris (called the stroma) can make eyes appear brown, blue or green. In the P protein, the mutation causes residue 419 to change from an arginine to a glutamine. 1991; Chintamaneni et al. Biogeographical ancestry admixture proportions were determined using the methods of Hanis et al. To identify SNP loci associated with variable human pigmentation, we genotyped for 754 SNPs: 335 SNPs within pigmentation genes (AP3B1, ASIP, DCT, MC1R, OCA2, SILV, TYR, TYRP1, MYO5A, POMC, AIM, AP3D1, and RAB; Table 1), and 419 other SNPs distributed throughout the genome. With the revelation of this epistatic relationship, it helps to prove that it can, and does, happen. PLoS Genet 6, e1000934 (2010). Antagonist color refers to the color with which the sequence is negatively associated. The process that produces melanin, known as melanogenesis, requires numerous proteins. 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. In the traditional view of eye color, it was taught that two blue-eyed individuals could only produce blue-eyed offspring. Although most TYR-negative OCA patients are completely depigmented, dark-iris albino mice (C44H) and their human type IB oculocutaneous counterparts exhibit a lack of pigment in all tissues except for the iris (Schmidt and Beermann 1994). A simple cross is provided in Figure 1: Blue-eyed Cross. Amplification products were subcloned into the pTOPO (Invitrogen, San Diego) sequencing vector and 96 insert-positive colonies were grown for plasmid DNA isolation (the use of 670 individuals for the amplification step reduced the likelihood of an individual contributing more than once to this subset of 96 selected). 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. Article Eye color is determined by the pattern of brown and red pigment, collagen fibers, and the topography of the iris. Edridge Green Lecture RCOphth Annual Congress Glasgow May 2019, A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia, A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness, A large Canadian cohort provides insights into the genetic architecture of human hair colour, Environment and culture shape both the colour lexicon and the genetics of colour perception, A systematic review of skin ageing genes: gene pleiotropy and genes on the chromosomal band 16q24.3 may drive skin ageing, White matter variability, cognition, and disorders: a systematic review, Quantitative changes in iris vasculature and blood flow in patients with different refractive errors, The Effect of Ambient Light Conditions on Quantitative Pupillometry, Functional and pathological relevance of HERC family proteins: a decade later. We have applied a nonsystematic, hypothesis-driven genome-screening approach to identify various SNPs, haplotypes, and diplotypes marginally (i.e., independently) associated with iris color variation. .. Chintamaneni C D, Ramsay M, Colman M-A, Fox M F, Pickard R T et al. Slider with three articles shown per slide. Sturm, R., Duffy, D., Zhao, Z., Leite, F., Stark, M., Hayward, N. et al. Similar to membrane-associated transporter protein, it transports melanosomes, but additionally, it controls their pH.3, 13 Therefore, the P protein encoded by OCA2 affects the amount and quality of melanin that deposits in melanocytes. Interestingly, the number of genes in human DNA is not appreciably different from the number of genes in chimpanzees or mice. Cassidy, S. B. (1995) and Koppula et al. record your observations. Place the PTC paper on your tongue for a few seconds. OCA2 ranges from 15q11.2-12 and HERC 2 starts at 15q13. The large HERC2 gene requires 211kb and 93 exons that codes for a 528kDa protein made of 4834 residues.12. From a screen of 754 SNP loci, we have identified 61 that are statistically associated with variable iris pigmentation at one level of intragenic complexity or another. Many of these strains exhibit biologically and medically relevant phenotypes, including pigment dispersion, a common feature of several human ocular diseases. 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. 1994, 1996), tyrosinase-like protein (TYRP1; Abbott et al. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. TYR, located from 11q14-q21, begins the melanogenesis pathway. P_ Pigmented Iris (Additional genes give specific color, e.g. Brilliant, M. The mouse p (pink-eyed dilution) and human P genes, ocular albinism type 2 (OCA2), and melanosomal pH. 1997; Lloyd et al. Knoll, J. H. M., Nicholls, R. D., Magenis, R. E., Glatt, K., Graham, Jr J. M., Kaplan, L. 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. 2001) are necessary for normal human iris pigmentation. Having little effect on eye color, many of them deal primarily with hair and skin pigmentation. The red appearance is the reflection of the eye's blood vessels. Rinchik, E. M., Bultman, S. J., Horsthemke, B., Lee, S., Strunk, K. M., Spritz, R. A. et al. Comparing the results of the two methods of classification, 86 of the classifications matched. 39, 14431452 (2007). White, D., Rabago-Smith, M. Genotypephenotype associations and human eye color. 2001) and that disparate regions of the TYR and other OCA genes are functionally distinct for determining the pigmentation in different tissues. When there is too little pigment to produce a strong blue color, the red reflections interact with the small amount of blue, producing a violet color.3, The biological process for producing melanin, melanogenesis, involves numerous protein interactions. Melanin undergoes a packaging process and if large amounts of P protein are not available to process and transport it, the quality of the darker pigment is compromised and lighter shades will result.14 Demonstrating epistasis, the HERC2 gene affects the results produced by the OCA2 gene. In the pheomelanin pathway, the presence of cysteine has a major role. 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. These two seemingly unrelated genes have a major effect on eye color in humans. Indeed, the associations were observed to be generally stronger for the SNPs in the context of within-gene haplotypesa result that would not necessarily be obtained for individual SNPs spuriously associatedsuggesting that the gene sequences themselves are associated, not merely a spurious polymorphism within each gene. To determine the extent to which extant iris color variation could be explained by various models, we calculated R2 values for SNPs, haplotypes, and multilocus genotype data by first assigning the phenotypic value for blue eye color as 1, green eye color as 2, hazel eye color as 3, and brown eye color as 4. .. Frudakis T, Venkateswarlu K, Thomas M J, Gaskin Z, Ginjupalli S et al. Pigmented irises. In the case of the mutation within HERC2, the expression of the P protein encoded by OCA2 decreases, effectively decreasing its effects in pigmentation. Most of what we have learned about pigmentation since has been derived from molecular genetics studies of rare pigmentation defects in humans and model systems such as mouse and Drosophila. Genetics 165, 20712083 (2003). 1, 105110 (2007). Sequences of the highest order of complexity within a locus found to be associated with iris colors. IRIS pigmentation is a complex genetic trait that has long interested geneticists, anthropologists, and the public at large. Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers. Eye color results from varying degrees of melanin produced in the melanocytes of the iris. .. Ooi C E, Moreira J E, DellAngelica E C, Poy G, Wassarman D A et al. Eye color genes. Similar to a lack of TYR, other conditions cause ocular albinism. There are two. 37.10 Cosmetic iris implant. For each gene, we inferred haplotypes and used contingency analyses to determine which haplotypes were statistically associated with iris colors. They help with hormone secretion, which affects the pituitary and can lead to dysfunction of the hypothalamus and other protein complexes. This finding, while common with albinism, is not specific as iris transillumination occurs in diseases unrelated to albinism such as pseudoexfoliation, pigment dispersion syndrome . Box N F, Wyeth J R, OGorman L E, Martin N G, Sturm R A. .. Gardner J M, Nakatsu Y, Gondo Y, Lee S, Lyon M F et al. Sequences associated with human iris pigmentation. What is the likely genotype of individual C-4? They also have little or no coloration in the iris of the eye, giving their eyes a pale blue or pink appearance. Over 300 SNPs for eye color have been identified on the gene, but classification of their results proved too arduous. 1996), melanocortin receptor (MC1R; Robbins et al. Already, some researchers have started studying hues and saturations. Alternatively, the mechanism for the associations could be LD with phenotypically active loci in nearby pigment genes. 1997). The next steps in eye color research involve hue classification among populations. Pathway I contains gene A that produces an enzyme to catalyze conversion of a colorless pigment designated white1 to blue pigment. However, single-gene studies have not provided a sound basis for understanding the complex genetics of human iris color. The first is that for most of the genes for which we identified marginally associated SNPs, multiple such SNPs were identified. Molecular and General Genet. 2001). The sequences for most of these genes vary significantly as a function of population structure (Frudakis et al. (H represents the non-mutated HERC2 SNP, and O represents the OCA2 allele for brown eyes). In Drosophila, iris pigmentation defects have been ascribed to mutations in >85 loci contributing to a variety of cellular processes in melanocytes (Ooi et al. Teaching the genetics of eye colour & colour vision. Although cysteine is not an essential amino acid and its deficiency rarely occurs, the lack of it halts the production of pheomelanin. Montserrat Rabago-Smith. The traits that are expressed make up your "phenotype" The allele that is not expressed is the "recessive" allele Fig. Dopachrome tautomerase (13q32) and TYR-related protein 1 (9p23) will continue the pathway to form eumelanin.15 Therefore, if any of these proteins are not coded for correctly, the eumelanin production may be hindered, producing lighter eyes. Hum Genet 123, 177187 (2008). On the basis of population studies, scientists speculate that the blue-eyed mutation originated in peoples of Northern Europe (Scandinavian countries). 1997, 2001; Akey et al. Google Scholar. Department of Chemistry and Biochemistry, Kettering University, Flint, MI, USA, You can also search for this author in In addition, we independently isolated the red hair/blue iris SNP alleles described by Valverde et al. The OCA2 gene also contains numerous regions for eye color expression. .. Rebbeck T R, Kanetsky P A, Walker A H, Holmes R, Halpern A C et al. OCA2 contains regions for the numerous eye colors, but one SNP is a strong predictor for brown/blue eyes. In other words, the distribution of SNPs among the various gene types was also not random. ), Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur, Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects, Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans, Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family, Molecular basis of mouse Himalayan mutation, A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12, Molecular structure and chromosomal mapping of the human homolog of the agouti gene, Diverse mutations of the P gene among African-Americans with type II (tyrosinase-positive) oculocutaneous albinism (OCA2), Induction of tyrosinase gene transcription in human iris organ cultures exposed to latanoprost, Not just pretty eyes: Drosophila eye-colour mutations and lysosomal delivery, Genetic and molecular analysis of recessive alleles at the pink-eyed dilution (p) locus of the mouse, Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4, Mutations within the promoter region of the tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. For example, skin color and height are determined by many genes. Genotypes were subject to several quality controls: two scientists independently pass/fail inspected the calls, requiring an overall UHT signal intensity >1000 for >95% of genotypes and clear signal differential between the averages for each genotype class (i.e., clear genotype clustering in two-dimensional space using the UHT analysis software). Despite the color of the eye, the number of melanocytes does not differ. This epistatic relationship demonstrates the significance of introns and how a single-base change greatly affects an aspect of the individual.
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