It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. In the case of TYR, melanin production will halt entirely, resulting in albinism in the entire body. What is the likely genotype of individual C-4? We selected those for which at least two instances of PHRED identified variants that scored 24, and each of these SNPs discovered through resequencing were used for genotyping. Genetic determinants of hair, eye and skin pigmentation in Europeans. ISSN 1434-5161 (print), Genotypephenotype associations and human eye color, Further insight into the global variability of the OCA2-HERC2 locus for human pigmentation from multiallelic markers, The distinctive geographic patterns of common pigmentation variants at the OCA2 gene, Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability, What colour are your eyes? Thank you for visiting nature.com. We also identified associations in the ASIP gene, which supports previous work by Kanetsky et al. ), 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. Human Earlobe attachment. brown, hazel) pp Blue Iris (non-pigmented) PG-1: In a human population exhibiting Hardy-Weinberg Equilibrium for the eye pigmentation gene, 81% of the people have blue (non-pigmented) irises. Article Zhu, G., Evans, D., Duffy, D., Montgomery, G., Medland, S., Gillespie, N. A. et al. Depending on how little pigment the melanocytes produce, albinism causes red or violet eyes. 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. A battery of genetic tests, of which one for the inference of iris color could be a part, could enable the construction of a more objective and science-based (partial) physical profile from crime-scene DNA, and an investigator using these tests would be less interested in the biological mechanism of the phenotype than in an ability to make an accurate inference of trait value. 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. Over 300 SNPs for eye color have been identified on the gene, but classification of their results proved too arduous. Even at this level of complexity, the sequences from no single gene could be used to make reliable iris color inferences, which suggests an element of intergenic complexity (i.e., epistasis) for iris color determination as well. 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. Complete the table. As the eye color lightens, less melanin is present in the cells, reflecting more of the visible spectrum. However, a number of the associations we identified were for SNPs located in other types of genes. Pigment Cell Res 14, 8693 (2001). Fig. If you exhibit the dominant phenotype, use a dash to represent the second allele. .. King R A, Townsend D, Oetting W S, Spritz R A. Klebig M L, Wilkinson J E, Geisler J G, Woychik R P. Koppula S V, Robbins L S, Lu D, Baack E, White C RJr. Here, we present an analysis of iris phenotypes among 16 mouse strains with mutations influencing melanosomes. 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. SNPs for the MC1R (16q24), SILV (12q13), and TYR (11q) genes and for the MAOA-Xp11.411.3 and GSTT2-22q11.23 regions were also found to be associated at the level of the haplotype (Tables 3 and 4), although these were the only regions of these chromosomes for which associations were found. Human pigmentation genes break out into several biochemical pathways, including those for tyrosinase enzyme complex formation on the inner surface of the melanosome, hormonal and environmental regulation, melanoblast migration and differentiation, the intracellular routing of new proteins into the melanosome, and the proper transportation of the melanosomes from the body of the cell into the dendritic arms toward the keratinocytes. Transcribed image text: P>p Trait Genotype Phenotypic Effect Relationship P. Pigmented Iris (Additional genes give specific Iris Color color, e.g. The sequences for most of these genes vary significantly as a function of population structure (Frudakis et al. IRIS pigmentation is a complex genetic trait that has long interested geneticists, anthropologists, and the public at large. PubMed Central Having little effect on eye color, many of them deal primarily with hair and skin pigmentation. Google Scholar. 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. This finding, while common with albinism, is not specific as iris transillumination occurs in diseases unrelated to albinism such as pseudoexfoliation, pigment dispersion syndrome . Sulem, P., Gudbjartsson, D., Stacey, S., Helgason, A., Rafnar, T., Magnusson, K. P. et al. 1991; Boissy et al. Sturm, R. & Frudakis, T. Eye Colour: portals into pigmentation genes and ancestry. 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. Representatives of the resulting PCR products were checked on an agarose gel, and first-round PCR product was diluted and then used as template for a second round of PCR. (H represents the non-mutated HERC2 SNP, and O represents the OCA2 allele for brown eyes). When this work is more fully developed, it may be possible to assign an iris color to an individual sample with reasonable certainty, and surely in this case the results herein will have some tangible value for the field of forensic science. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. (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). There are two. Chi-square P value is shown. These two seemingly unrelated genes have a major effect on eye color in humans. The reason many white, non-Hispanic babies are born with blue eyes is that they don't have the full amount of melanin present in their irises at birth. Box N F, Duffy D L, Irving R E, Russell A, Chen W et al. (2002). Eumelanin (brown pigment) is a light-absorbing polymer synthesized in specialized melanocyte lysosomes called melanosomes. & WojasPelc, A. Interactions between HERC2, OCA2, and MC1R may influence human pigmentation phenotype. homework 5 ans. 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. 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. This provides an explanation why some babies develop their eye color, but skin pigmentation changes constantly throughout life. MGG 1, 393394 (1908). More than likely, their offspring would have blue eyes, but a 25% chance stands that offspring would have brown eyes. When a T is replaced with a C in rs12913832 of intron 86, OCA2 transcription is depressed, resulting in a blue-eyed individual. An individual that is homozygous W is much more likely to have blue iris, exhibiting odds 77.25-times larger than the odds of having blue irises of a genotype other than W/W (P < 0.0001). Knoll, J. H. M., Nicholls, R. D., Magenis, R. E., Glatt, K., Graham, Jr J. M., Kaplan, L. et al. Even if the OCA2 gene contains the alleles for brown eyes, the SNP in intron 86 of HERC2 will prevent its expression. Nat Genet. ., Oxford University Press is a department of the University of Oxford. .. Schioth H B, Phillips S R, Rudzish R, Birch-Machin M A, Wikberg J E et al. Hum Genet 123, 177187 (2008). 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. Slider with three articles shown per slide. However, the results presented herein constitute a good first step toward solving what our results confirm is a very complex genetics problem. 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 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. The eumelanin/pheomelanin switch triggered by the MC1R gene may account for some cases of this disorder. 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. (1986) and Shriver et al. An intron in HERC2 contains the promoter region for OCA2, affecting its expression. Place the PTC paper on your tongue for a few seconds. Both genes are located on chromosome 15. Branicki, W., Brudnik, U. 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. OCA2 associations were by far the most significant of any gene or region we tested, while MYO5A SNPs were only weakly associated (but haplotypes and diplotypes more strongly). Molecular and General Genet. Although corrections for multiple testing left most of the SNP-level associations intact, a number of the associations we found did not pass the multiple-testing examination, but nonetheless we present them here to avoid possible type II error; the sequences may be weakly associated with iris colors and possibly relevant within a multiple-gene model for classification (i.e., epistasis). Use a lab partner to help you determine your phenotype for the traits listed. Box N F, Wyeth J R, OGorman L E, Martin N G, Sturm R A. Now, that color depends on the kind and density of melanin a person is born with. To form eumelanin, dopachrome tautomerase, TYR, and TYR-related protein 1 complete the chemical pathway from dopaquinone.3, Although the aforementioned proteins are responsible for the production of melanin, once it has been produced in the melanosomes, other proteins are responsible for melanin maturation. 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. Different SNPs on these two genes were investigated and analyzed for melanoma risk.24, 25. Apart from representing the first comprehensive candidate gene study for variable iris pigmentation and constituting a first step toward developing a classification model for the inference of iris color from DNA, our results suggest that cryptic population structure might serve as a leverage tool for complex trait gene mapping if genomes are screened with the appropriate ancestry informative markers. In the meantime, to ensure continued support, we are displaying the site without styles This is an example of a hihybrid crosses. (d) List the possible genotypes of a blue eyed individual lacking a dimpled chin. A dark iris pigment (green/brown/black) is dominant over the light pigmentation. PubMed However, this result would not have necessarily been obtained were we working with SNPs that were not truly associated with iris colors. https://doi.org/10.1038/jhg.2010.126, DOI: https://doi.org/10.1038/jhg.2010.126. 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. bb genotype for the phenotype of blue eyes. .. 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. The disorder is characterized by different-colored irises or different colors within the iris. The recessive allele (b) encodes blue eyes. PubMed B_ genotype for the phenotype of brown eyes (dash indicates second allele could be B or b which means a genotype of BB or Bb) genotype - all alleles present in the cell ; phenotype - physical appearance of a trait ; . 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. (2000) with adjusted residuals to compensate for this risk. The possible changes in the DNA sequence are GCT to GTT and GCC to GTC. To determine whether and how common polymorphisms are associated with natural distributions of iris colors, we surveyed 851 individuals of mainly European descent at 335 SNP loci in 13 pigmentation genes and 419 other SNPs distributed throughout the genome and known or thought to be informative for certain elements of population structure. 1995; Koppula et al. The second parent has a non-mutated HERC2 allele but does not have the coding for brown eyes in the OCA2 gene. 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. 37.10 Cosmetic iris implant. At the level of the haplotype, each gene or region had unique numbers and types of associations. 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. 1997; Smith et al. Although there are about 16 different genes responsible for eye color, it is mostly attributed to two adjacent genes on chromosome 15, hect domain and RCC1-like domain-containing protein 2 (HERC2) and ocular albinism (that is, oculocutaneous albinism II (OCA2)). The solid figures represent albino individuals. Genotype-phenotype correlations have been reported with specific mutations possibly associated with certain angle abnormalities. On the basis of population studies, scientists speculate that the blue-eyed mutation originated in peoples of Northern Europe (Scandinavian countries). In the case of the mutation within HERC2, the expression of the P protein encoded by OCA2 decreases, effectively decreasing its effects in pigmentation. ), 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. brown, hazel) P > p. pp. BLAST searches confirmed the specificity of all primers used. In this case, pleiotropic effects change eye color. The "P" allele produces the pigment which gives you eye color. 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. .. 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. et al. The minor allele frequency for most of these SNPs was relatively high (average F minor allele = 0.22) and most of them were in Hardy-Weinberg equilibrium (HWE; those for which HWE P > 0.05, 28/34; Table 3). 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 . 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. PubMed Eumelanin (brown pigment) is a light-absorbing polymer synthesized in specialized melanocyte lysosomes called melanosomes. Pigmented iris A person with the B allele has brown eyes. 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). 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. If no haplotypes were found to be associated for a locus but diplotypes were found to be associated, both the haplotypes and the diplotypes are shown. 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. .. Bito L Z, Matheny A, Cruickshanks K J, Nondahl D M, Carino O B. Boissy R E, Zhao H, Oetting W S, Austin L M, Wildenberg S C et al. Article A genome scan for eye color in 502 twin families: most variation is due to a QTL on chromosome 15q. 2000). 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. Red and violet eyes come from a lack of pigment. For example, unlike human hair color (Sturm et al. Am J Hum Genet 82, 424431 (2008). In addition, we independently isolated the red hair/blue iris SNP alleles described by Valverde et al. When a pigment is deposited in the front layer of the iris, this masks the blue layer to varying degrees. _____ Pigmented Iris If you are homozygous for the recessive allele "p", you do not produce pigment in the front layer of your iris. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Eye color ranges include varying shades of brown, hazel, green, blue, gray, and in rare cases, violet and red. 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. P_ Pigmented Iris (Additional genes give specific color, e.g. Once the pigment is produced, MC1R, membrane-associated transporter protein, and p proteins (OCA2) mature the melanosomes to be used in the cells. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Alternatively, as a research tool, the common haplotypes that we have identified and the complex, biologically relevant contexts within which they are found may help researchers more accurately define risk factors for pigmentation-related diseases such as cataracts and melanoma. All of the major sequences (count 13) for each locus with at least one significantly associated sequence are shown. 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. Sturm, R., Duffy, D., Zhao, Z., Leite, F., Stark, M., Hayward, N. et al. 1995). Most of the marginally associated SNPs were found within the pigmentation genes OCA2 (n = 10), TYRP1 (n = 4), AIM (n = 3), MYO5A (n = 2), and DCT (n =, SNPs marginally (independently) associated with iris pigmentation and SNPs associated only within the context of haplotypes and/or diplotypes. Hardy-Weinberg equilibrium P value, where a value <0.05 indicates that the alleles are not in equilibrium. 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 . In the population sample, we were also able to examine the correlation between genotype at the W locus and iris color . PubMed Central The overlap among these SNP sets was high but not perfect. Phenotypic Effect. 2001). 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. Accessibility StatementFor more information contact us atinfo@libretexts.orgor check out our status page at https://status.libretexts.org. In the absence of melanin brown pigment, the iris is blue. Resequencing for these genes was performed by amplifying the proximal promoter (average 700 bp upstream of transcription start site), each exon (average size 1400 bp), the 5 and 3 ends of each intron (including the intron-exon junctions, average size 100 bp), and 3 untranslated region (UTR; average size 700 bp) sequences from a multi-ethnic panel of 672 individuals (450 individuals from the Coriell Institute's DNA Polymorphism Discovery Resource, 96 additional European Americans, 96 African Americans, 10 Pacific Islanders, 10 Japanese, and 10 Chinese; these 672 individuals represented a set of samples separate from that used for the association study described herein). 2001) are necessary for normal human iris pigmentation. Incomplete dominance shows in individuals with lighter shades of brown and hazel. record your observations. All visible light is absorbed by the retina. They also have little or no coloration in the iris of the eye, giving their eyes a pale blue or pink appearance. 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). .. Copeland N G, Hutchison K W, Jenkins N A. Durham-Pierre D, Gardner J M, Nakatsu Y, King R A, Francke U et al. Forensic Sci Int: Genet. For example, skin color and height are determined by many genes. You are using a browser version with limited support for CSS. OCA2 contains regions for the numerous eye colors, but one SNP is a strong predictor for brown/blue eyes. Eye color genes. 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. 1998; Schioth et al. 1998; Flanagan et al. Linkage studies have implicated certain pigmentation genes as specifically relevant for pigmentation phenotypes, and most of the pigmentation gene SNPs that we identified clustered to certain genes such as OCA2, MYO5A, TYRP1, and AIM. 1991; Chintamaneni et al. Hum Mutat 13, 99115 (1999). .. Ooi C E, Moreira J E, DellAngelica E C, Poy G, Wassarman D A et al. Pigmented Iris If you are homozygous for the recessive allele "p", you do not produce pigment in the front layer of your iris. .. Hamabe J, Fukushima Y, Harada N, Abe K, Matsuo N et al.