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Molecular genetics of color-vision deficiencies

  • SAMIR S. DEEB (a1)

Abstract

The normal X-chromosome-linked color-vision gene array is composed of a single long-wave-sensitive (L-) pigment gene followed by one or more middle-wave-sensitive (M-) pigment genes. The expression of these genes to form L- or M-cones is controlled by the proximal promoter and by the locus control region. The high degree of homology between the L- and M-pigment genes predisposed them to unequal recombination, leading to gene deletion or the formation of L/M hybrid genes that explain the majority of the common red–green color-vision deficiencies. Hybrid genes encode a variety of L-like or M-like pigments. Analysis of the gene order in arrays of normal and deutan subjects indicates that only the two most proximal genes of the array contribute to the color-vision phenotype. This is supported by the observation that only the first two genes of the array are expressed in the human retina. The severity of the color-vision defect is roughly related to the difference in absorption maxima (λmax) between the photopigments encoded by the first two genes of the array. A single amino acid polymorphism (Ser180Ala) in the L pigment accounts for the subtle difference in normal color vision and influences the severity of red–green color-vision deficiency.

Blue-cone monochromacy is a rare disorder that involves absence of L- and M-cone function. It is caused either by deletion of a critical region that regulates expression of the L/M gene array, or by mutations that inactivate the L- and M-pigment genes. Total color blindness is another rare disease that involves complete absence of all cone function. A number of mutants in the genes encoding the cone-specific α- and β-subunits of the cGMP-gated cation channel as well as in the α-subunit of transducin have been implicated in this disorder.

Copyright

Corresponding author

Address correspondence and reprint requests to: Samir S. Deeb, Division of Medical Genetics, BOX 357720, University of Washington, Seattle, WA 98195, USA. E-mail sdeeb@washington.edu

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REFERENCES

Alpern, M. (1979). Lack of uniformity in colour matching. Journal of Physiology 288, 85105.
Arbour, N.C., Zlotogora, J., Knowlton, R.G., Merin, S., Rosenmann, A., Kanis, A.B., Rokhlina, T., Stone, E.M., & Sheffield, V.C. (1997). Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling. Human Molecular Genetics 6, 689694.
Asenjo, A.B., Rim, J., & Oprian, D.D. (1994). Molecular determinants of human red/green color discrimination. Neuron 12, 11311138.
Ayyagari, R., Kakuk, L.E., Bingham, E.L., Szczesny, J.J., Kemp, J., Toda, Y., Felius, J., & Sieving, P.A. (2000). Spectrum of color gene deletions and phenotype in patients with blue cone monochromacy. Human Genetics 107, 7582.
Crognale, M.A., Teller, D.Y., Motulsky, A.G., & Deeb, S.S. (1998). Severity of color vision defects: Electroretinographic (ERG), molecular and behavioral studies. Vision Research 38, 33773385.
Crognale, M.A., Teller, D.Y., Yamaguchi, T., Motulsky, A.G., & Deeb, S.S. (1999). Analysis of red/green color discrimination in subjects with a single X-linked photopigment gene. Vision Research 39, 707719.
Deeb, S.S. & Kohl, S. (2003). Genetics of color vision deficiencies. Developmental Ophthalmology 37, 170187.
Deeb, S.S., Lindsey, D.T., Hibiya, Y., Sanocki, E., Winderickx, J., Teller, D.Y., & Motulsky, A.G. (1992). Genotype-phenotype relationships in human red/green color-vision defects: Molecular and psychophysical studies. American Journal of Human Genetics 51, 687700.
Feil, R., Aubourg, P., Heilig, R., & Mandel, J.L. (1990). A 195-kb cosmid walk encompassing the human Xq28 color vision pigment genes. Genomics 6, 367373.
Hayashi, T., Motulsky, A.G., & Deeb, S.S. (1999). Position of a ‘green-red’ hybrid gene in the visual pigment array determines colour-vision phenotype. Nature Genetics 22, 9093.
He, J.C. & Shevell, S.K. (1995). Variation in color matching and discrimination among deuteranomalous trichromats: Theoretical implications of small differences in photopigments. Vision Research 35, 25792588.
Hess, R.F., Mullen, K.T., Sharpe, L.T., & Zrenner, E. (1989). The photoreceptors in atypical achromatopsia. Journal of Physiology (London) 417, 123149.
Jagla, W.M., Jagle, H., Hayashi, T., Sharpe, L.T., & Deeb, S.S. (2002). The molecular basis of dichromatic color vision in males with multiple red and green visual pigment genes. Human Molecular Genetics 11, 2332.
Jordan, G. & Mollon, J.D. (1993). A study of women heterozygous for colour deficiencies. Vision Research 33, 14951508.
Kohl, S., Baumann, B., Broghammer, M., Jagle, H., Sieving, P., Kellner, U., Spegal, R., Anastasi, M., Zrenner, E., Sharpe, L.T., & Wissinger, B. (2000). Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Human Molecular Genetics 9, 21072116.
Kohl, S., Baumann, B., Rosenberg, T., Kellner, U., Lorenz, B., Vadala, M., Jacobson, S.G., & Wissinger, B. (2002). Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. American Journal of Human Genetics 71, 422425.
Kohl, S., Marx, T., Giddings, I., Jagle, H., Jacobson, S.G., Apfelstedt-Sylla, E., Zrenner, E., Sharpe, L.T., & Wissinger, B. (1998). Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nature Genetics 19, 257259.
Merbs, S.L. & Nathans, J. (1992a). Absorption spectra of human cone pigments. Nature 356, 433435.
Merbs, S.L. & Nathans, J. (1992b). Absorption spectra of the hybrid pigments responsible for anomalous color vision. Science 258, 464466.
Motulsky, A.G. & Deeb, S.S. (2001). Color vision and its genetic defects. In The Metabolic and Molecular Bases of Inherited Disease, Vol. IV, eighth edition ed. Scriver, C.R., Beaudet, A.L., Sly, W.S. & Valle, D., pp. 59555976. New York: McGraw-Hill.
Nathans, J., Davenport, C.M., Maumenee, I.H., Lewis, R.A., Hejtmancik, J.F., Litt, M., Lovrien, E., Weleber, R., Bachynski, B., Zwas, F., Traboulsi, E., Klingaman, R., Bech-Hansen, N.T., LaRouche, G.R., Pagon, R.A., Murphey, W.H., & Weleber, R.G. (1989). Molecular genetics of human blue cone monochromacy. Science 245, 831838.
Nathans, J., Maumenee, I.H., Zrenner, E., Sadowski, B., Sharpe, L.T., Lewis, R.A., Hansen, E., Rosenberg, T., Schwartz, M., Heckenlively, J.R., Traboulsi, E., Klingaman, R., Bech-Hansen, N.T., LaRouche, G.R., Pagon, R.A., Murphey, W.H., & Weleber, R.G. (1993). Genetic heterogeneity among blue-cone monochromats. American Journal of Human Genetics 53, 9871000.
Nathans, J., Piantanida, T.P., Eddy, R.L., Shows, T.B., & Hogness, D.S. (1986a). Molecular genetics of inherited variation in human color vision. Science 232, 203210.
Nathans, J., Thomas, D., & Hogness, D.S. (1986b). Molecular genetics of human color vision: The genes encoding blue, green, and red pigments. Science 232, 193202.
Neitz, J. & Jacobs, G.H. (1986). Polymorphism of the long-wave cone in normal human colour vision. Nature 323, 623625.
Neitz, J., Neitz, M., & Jacobs, G.H. (1989). Analysis of fusion gene and encoded photopigment of colour-blind humans. Nature 342, 679682.
Neitz, M., Neitz, J., & Jacobs, G.H. (1991). Spectral tuning of pigments underlying red–green color vision. Science 252, 971974.
Neitz, J., Neitz, M., & Kainz, P.M. (1996). Visual pigment gene structure and the severity of color vision defects. Science 274, 801804.
Peng, C., Rich, E.D., & Varnum, M.D. (2003). Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels. Journal of Biological Chemistry 278, 3453334540.
Sanocki, E., Teller, D.Y., & Deeb, S.S. (1997). Rayleigh match ranges of red/green color-deficient observers: Psychophysical and molecular studies. Vision Research 37, 18971907.
Sharpe, L.T., Stockman, A., Jagle, H., Knau, H., Klausen, G., Reitner, A., & Nathans, J. (1998). Red, green, and red–green hybrid pigments in the human retina: Correlations between deduced protein sequences and psychophysically measured spectral sensitivities. Journal of Neuroscience 18, 1005310069.
Sharpe, L.T., Stockman, A., Jagle, H., Knau, H., & Nathans, J. (1999a). L, M and L–M hybrid cone photopigments in man: Deriving lambda max from flicker photometric spectral sensitivities. Vision Research 39, 35133525.
Sharpe, L.T., Stockman, A., Jagle, H., & Nathans, J. (1999b). Opsin genes, cone photopigments, color vision, and color blindness. In Color Vision, from Genes to Perception, ed. Gegenfurtener, K.R. & Sharpe, L.T., pp. 351. Cambridge, UK: Cambridge University Press.
Smallwood, P.M., Wang, Y., & Nathans, J. (2002). Role of a locus control region in the mutually exclusive expression of human red and green cone pigment genes. Proceedings of the National Academy of Sciences of the U.S.A. 99, 10081011.
Sundin, O.H., Yang, J.M., Li, Y., Zhu, D., Hurd, J.N., Mitchell, T.N., Silva, E.D., & Maumenee, I.H. (2000). Genetic basis of total colourblindness among the Pingelapese islanders. Nature Genetics 25, 289293.
Ueyama, H., Li, Y.H., Fu, G.L., Lertrit, P., Atchaneeyasakul, L.O., Oda, S., Tanabe, S., Nishida, Y., Yamade, S., & Ohkubo, I. (2003). An A-71C substitution in a green gene at the second position in the red/green visual-pigment gene array is associated with deutan color-vision deficiency. Proceedings of the National Academy of Sciences of the U.S.A. 100, 33573362.
Vollrath, D., Nathans, J., & Davis, R.W. (1988). Tandem array of human visual pigment genes at Xq28. Science 240, 16691672.
Wang, Y., Macke, J.P., Merbs, S.L., Zack, D.J., Klaunberg, B., Bennett, J., Gearhart, J., & Nathans, J. (1992). A locus control region adjacent to the human red and green visual pigment genes. Neuron 9, 429440.
Wang, Y., Smallwood, P.M., Cowan, M., Blesh, D., Lawler, A., & Nathans, J. (1999). Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors. Proceedings of the National Academy of Sciences of the U.S.A. 96, 52515256.
Weitz, C.J., Miyake, Y., Shinzato, K., Montag, E., Zrenner, E., Went, L.N., & Nathans, J. (1992a). Human tritanopia associated with two amino acid substitutions in the blue-sensitive opsin. American Journal of Human Genetics 50, 498507.
Weitz, C.J., Went, L.N., & Nathans, J. (1992b). Human tritanopia associated with a third amino acid substitution in the blue-sensitive visual pigment [letter]. American Journal of Human Genetics 51, 444446.
Winderickx, J., Battisti, L., Motulsky, A.G., & Deeb, S.S. (1992a). Selective expression of human X chromosome-linked green opsin genes. Proceedings of the National Academy of Sciences of the U.S.A. 89, 97109714.
Winderickx, J., Battisti, L., Hibiya, Y., Motulsky, A.G., & Deeb, S.S. (1993). Haplotype diversity in the human red and green opsin genes: Evidence for frequent sequence exchange in exon 3. Human Molecular Genetics 2, 14131421.
Winderickx, J., Lindsey, D.T., Sanocki, E., Teller, D.Y., Motulsky, A.G., & Deeb, S.S. (1992b). Polymorphism in red photopigment underlies variation in colour matching. Nature 356, 431433.
Winderickx, J., Sanocki, E., Lindsey, D.T., Teller, D.Y., Motulsky, A.G., & Deeb, S.S. (1992c). Defective colour vision associated with a missense mutation in the human green visual pigment gene. Nature Genetics 1, 251256.
Winick, J.D., Blundell, M.L., Galke, B.L., Salam, A.A., Leal, S.M., & Karayiorgou, M. (1999). Homozygosity mapping of the Achromatopsia locus in the Pingelapese. American Journal of Human Genetics 64, 16791685.
Wissinger, B., Jagle, H., Kohl, S., Broghammer, M., Baumann, B., Hanna, D.B., Hedels, C., Apfelstedt-Sylla, E., Randazzo, G., Jacobson, S.G., Zrenner, E., & Sharpe, L.T. (1998). Human rod monochromacy: Linkage analysis and mapping of a cone photoreceptor expressed candidate gene on chromosome 2q11. Genomics 51, 325331.
Yamaguchi, T., Motulsky, A.G., & Deeb, S.S. (1997). Visual pigment gene structure and expression in human retinae. Human Molecular Genetics 6, 981990.
Yokoyama, S. (2002). Molecular evolution of color vision in vertebrates. Gene 300, 6978.
Yokoyama, S. & Radlwimmer, F.B. (1999). The molecular genetics of red and green color vision in mammals. Genetics 153, 919932.

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