Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Position of a 'green-red' hybrid gene in the visual pigment array determines colour-vision phenotype

Nature Genetics volume 22, pages 90–93 (1999)Cite this article

Abstract

The X-linked red- and green-pigment genes are arranged in a head-to-tail tandem array1,2,3. The colour-vision defect of deuteranomaly (in 5% of males of European descent) is associated with a 5´-green-red-3´ visual-pigment hybrid gene4,5, which may also exist in males with normal colour vision5,6,7. To explain why males with a normal red, a normal green and a green-red hybrid gene may have either normal or deutan colour vision, we hypothesized that only the first two genes are expressed8,9 and deuteranomaly results only if the green-red hybrid gene occupies the second position and is expressed preferentially over normal green-pigment genes occupying more distal positions. We used long-range PCR amplification and studied 10 deutan males (8 deuteranomalous and 2 deuteranopic) with 3 visual pigment genes (red, green and green-red hybrid) to investigate whether position of the hybrid gene in the array determined gene expression. The green-red hybrid gene was always at the second position (and the first position was always occupied by the red gene). Conversely, in two men with red, green and green-red hybrid genes and normal colour vision, the hybrid gene occupied the third position. When pigment gene mRNA expression was assessed in post-mortem retinae of three men with the red, green and green-red genotype, the green-red hybrid gene was expressed only when located in the second position. We conclude that the green-red hybrid gene will only cause deutan defects when it occupies the second position of the pigment gene array.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Visual pigment-gene array structure and investigative strategy.
Figure 2: Gel electrophoresis and Southern-blot analysis of the long-range PCR product.
Figure 3: Identity of the long-range PCR products.
Figure 4: Diagram illustrating the relationship of the position of the 5´-green-red-3´ (G-R) hybrid gene in the visual-pigment gene array to both the colour-vision phenotype and gene expression in the retina.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Nathans, J., Thomas, D. & Hogness, D.S. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 232 , 193–202 (1986).

    Article  CAS  Google Scholar 

  2. Vollrath, D., Nathans, J. & Davis, R.W. Tandem array of human visual pigment genes at Xq28. Science 240, 1669–1672 (1988).

    Article  CAS  Google Scholar 

  3. Feil, R., Aubourg, P., Heilig, R. & Mandel, J.L. A 195-kb cosmid walk encompassing the human Xq28 color vision pigment genes. Genomics 6, 367–373 ( 1990).

    Article  CAS  Google Scholar 

  4. Nathans, J., Piantanida, T.P., Eddy, R.L., Shows, T.B. & Hogness, D.S. Molecular genetics of inherited variation in human color vision. Science 232, 203–210 (1986).

    Article  CAS  Google Scholar 

  5. Deeb, S.S. et al. Genotype-phenotype relationships in human red/green color-vision defects: molecular and psychophysical studies. Am. J. Hum. Genet. 51, 687–700 ( 1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Drummond-Borg, M., Deeb, S.S. & Motulsky, A.G. Molecular patterns of X chromosome-linked color vision genes among 134 men of European ancestry. Proc. Natl Acad. Sci. USA 86, 983–987 ( 1989).

    Article  CAS  Google Scholar 

  7. Neitz, M. & Neitz, J. Numbers and ratios of visual pigment genes for normal red-green colour vision. Science 267 , 1013–1016 (1995).

    Article  CAS  Google Scholar 

  8. Winderickx, J., Battisti, L., Motulsky, A.G. & Deeb, S.S. Selective expression of human X chromosome-linked green opsin genes. Proc. Natl Acad. Sci. USA 89, 9710– 9714 (1992).

    Article  CAS  Google Scholar 

  9. Yamaguchi, T., Motulsky, A.G. & Deeb, S.S. Visual pigment gene structure and expression in human retinae. Hum. Mol. Genet. 6, 981– 990 (1997).

    Article  CAS  Google Scholar 

  10. Crognale, M.A., Teller, D.Y., Motulsky, A.G. & Deeb, S.S. Severity of color vision defects: electroretinographic (ERG), molecular and behavioral studies. Vision Res. 38, 3377 –3385 (1998).

    Article  CAS  Google Scholar 

  11. Farrell, D.F., Hamilton, S.R., Knauss, T.A., Sanocki, E. & Deeb, S.S. X-linked adrenoleukodystrophy: adult cerebral variant. Neurology 43, 1518– 1522 (1993).

    Article  CAS  Google Scholar 

  12. Hanna, M.C., Platts, J.T. & Kirkness, E.F. Identification of a gene within the tandem array of red and green color pigment genes. Genomics 43, 384–386 (1997).

    Article  CAS  Google Scholar 

  13. Merbs, S.L. & Nathans, J. Absorption spectra of the hybrid pigments responsible for anomalous color vision. Science 258, 464–466 (1992).

    Article  CAS  Google Scholar 

  14. Asenjo, A.B., Rim, J. & Oprian, D.D. Molecular determinants of human red/green color discrimination. Neuron 12, 1131–1138 (1994).

    Article  CAS  Google Scholar 

  15. Sjoberg, S.A., Neitz, M., Balding, S.D. & Neitz, J. L-cone pigment genes expressed in normal color vision. Vision Res. 38, 3213–3219 (1998).

    Article  CAS  Google Scholar 

  16. Neitz, J., Neitz, M. & Kainz, P.M. Visual pigment gene structure and the severity of color vision defects. Science 274, 801– 804 (1996).

    Article  CAS  Google Scholar 

  17. Shevell, S.K. & He, J.C. The visual photopigments of simple deuteranomalous trichromats inferred from color matching. Vision Res. 37, 1115–1127 ( 1997).

    Article  CAS  Google Scholar 

  18. Sharpe, L.T. et al. Red, green, and red-green hybrid pigments in the human retina: correlations between deduced protein sequences and psychophysically measured spectral sensitivities. J. Neurosci. 18, 10053–10069 (1998).

    Article  CAS  Google Scholar 

  19. Nathans, J. et al. Genetic heterogeneity among blue-cone monochromats. Am. J. Hum. Genet. 53, 987–1000 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang, Y. et al. A locus control region adjacent to the human red and green visual pigment genes. Neuron 9, 429– 440 (1992).

    Article  CAS  Google Scholar 

  21. Hanscombe, O. et al. High-level, erythroid-specific expression of the human α-globin gene in transgenic mice and the production of human hemoglobin in murine erythrocytes. Genes Dev. 3, 1572–1581 (1989).

    Article  CAS  Google Scholar 

  22. Dillon, N. & Grosveld, F. Human γ-globin genes silenced independently of other genes in the β-globin locus. Nature 350, 252–254 ( 1991).

    Article  CAS  Google Scholar 

  23. Sanocki, E., Teller, D.Y. & Deeb, S.S. Rayleigh match ranges of red/green color-deficient observers: psychophysical and molecular studies. Vision Res. 37, 1897–1907 (1997).

    Article  CAS  Google Scholar 

  24. Kitahara, K. Individual variations in color vision and its molecular biology. Nippon Ganka Gakkai Zasshi 102, 837– 849 (1998).

    CAS  PubMed  Google Scholar 

  25. Miller, S.A., Dykes, D.D. & Polesky, H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16, 1215 (1988).

    Article  CAS  Google Scholar 

  26. Macke, J.P. & Nathans, J. Individual variation in size of the human red and green visual pigment gene array. Invest. Ophthalmol. Vis. Sci. 38, 1040–1043 (1997).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank K. Kitahara and T. Yamaguchi for subject 6 DNA. This work was supported by NIH grant EY08395. T.H. was supported by a fellowship from the Department of Ophthalmology, Jikei University School of Medicine.

Author information

Authors and Affiliations

  1. Departments of Medicine and Genetics, University of Washington, Seattle, Washington, USA

    Takaaki Hayashi, Arno G. Motulsky & Samir S. Deeb

Authors
  1. Takaaki Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arno G. Motulsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samir S. Deeb
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samir S. Deeb.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hayashi, T., Motulsky, A. & Deeb, S. Position of a 'green-red' hybrid gene in the visual pigment array determines colour-vision phenotype. Nat Genet 22, 90–93 (1999). https://doi.org/10.1038/8798

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/8798

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing