Michael Morrison

University of New Hampshire - Manchester

mjm23@unh.edu

Color Blindness - OPN1LW gene mutation

Introduction:

Color blindness is a deficiency described as the decreased ability, or inability, to differentiate colors that affects over 3.5 million Americans. It was first described by English chemist John Dalton in his 1798 paper "Extraordinary facts relating to the vision of colours." It is diagnosed by the use of the Ishihara color test, which uses a series of pictures composed of colored dots (an example can be seen here). Although color blindness can be caused by brain or retinal damage caused by shaken baby syndrome, trauma that produces swelling of the brain or retinal ultra violet exposure, it is most often caused by genetic mutation to the X chromosome. Because it is a sex-linked trait on the X chromosome, it is more common in males than females. This is due to females extra X chromosome, meaning that both inherited x chromosomes must be defective for females to show signs of color blindness.

The most common form of color blindness is red-green colorblindness associated with individuals with protanopia, deuteranopia, protanomaly, and deuteranomaly. This is caused by a mutation in the OPN1LW gene on the X chromosome. This gene controls long-wavelength sensitive photopigments on cone photoreceptors in the retina. As the figure shows below, a nonsense mutation at nucleotide position 940 (G to A) changes codon 149 from the amino acid tryptophan to the TAG stop codon. This immaturely halts the production of the OPN1LW protein and produces a non-functioning protein instead.

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What do color blind people see?

Gene Location:

The Map Viewer is a bioinformatic tool that allows one to search for particular gene locations on chromosomes. As shown below, the OPN1LW gene is located on the X Chromosome.

external image map_search.cgi?taxid=9606&query=color+blindness&qchr=X&strain=All&NCkey=NCID_1_1593029_130.14.24.201_9100_1292251179_814689839&gif=1

Chromosome: X; Location: Xq28

external image geneneighb.fcgi?geneid=5956&nuc_gi=224589822&n0=MIR718&n1=MECP2&n2=OPN1LW&n3=TEX28P2&n4=OPN1MW&n5=TEX28P1

Sequence View

As seen above, the OPN1LW gene is located proximally upstream of the OPN1MW gene, which codes for the medium wavelength gene. This is important to point out since a mutation in the OPN1LW gene can hinder the production of the OPN1MW gene, this would result in an individual with complete color blindness.

BlastN Results: all matches had a E-value of 0.0

Human: Homo sapiens opsin 1 (cone pigments), long-wave-sensitive (OPN1LW) - 100% (reference)

Common Chimpanzee: Pan troglodytes chromosome X clone PTB-034D05 map Xq28, complete sequence - 100%

Sumatran Orangutan: Pongo abelii BAC clone CH276-298D10 from chromosome unknown - 96%

Yellow Baboon: Papio cynocephalus red color vision gene - 95%

BlastN

Phylogenic Tree:

tree.JPG

Gene Therapy:

Scientists at the University of Washington and the University of Florida have recently made a major breakthrough in the possibility of gene therapy as a cure for color blindness. Adding red sensitivity to cone cells in two color blind squirrel monkeys, Dr. William W. Hauswirth has been able to successfully cure the animals' color blindness. Dr. Hauswirth states that, "although color blindness is only moderately life-altering, we've shown we can cure a cone disease in a primate, and that it can be done very safely. That's extremely encouraging for the development of therapies for human cone diseases that really are blinding." Dr. Hauswirth and his colleagues used human genes to produce long-wavelength opsin to treat the monkeys, making it that much easier and more probable that a human cure can be produced. The therapy took 20 weeks to take effect, with no negative after effects. They used the Cambridge Colour Test and a touch screen computer program to determine that the monkeys can now decipher 16 hues of various colors and intensities.

Sources:

Wagner-Schuman, M. Color-deficient cone mosaics associated with Xq28 opsin mutations: A stop codon versus gene deletions.Vision Research Reviews. Vol 50, Iss 23, Pg 2396-2402, 23 Nov 2010. link

Cassin, B. and Solomon, S. Dictionary of Eye Terminology. Gainsville, Florida: Triad Publishing Company, 1990.

University of Florida. "Scientists Cure Color Blindness In Monkeys." ScienceDaily 16 September 2009. 13 December 2010. link

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