Joris Winderickx

Serine/Alanine Amino Acid Polymorphism of the L and M Cone Pigments: Effects on Rayleigh Matches among Deuteranopes, Protanopes and Color Normal Observers

In a first experiment, groups of deuteranopes and protanopes were characterized psychophysically by the slopes of regression lines fitted to yellow intensity settings from their Rayleigh matches. In a second experiment, color normal male subjects were characterized by their 2 and 8 deg Rayleigh match points. All subjects had been previously characterized genetically by the presence of the amino acid serine or alanine at position 180 on their L cone or L/M hybrid opsins. Dichromats and color normal subjects with serine had greater sensitivity to the red primary than did those with alanine. Calculations based on psychophysical results suggest that the substitution of serine by alanine in the L cone opsin or L/M hybrid opsin produces a shift in lambda max of the expressed pigment toward shorter wavelengths by an amount varying between 2.6 and 4.3 nm, with the shifts in lambda max for the dichromats being larger than those for the color normal subjects.

Molecular analysis of human red/green visual pigment gene locus: Relationship to color vision

Publisher Summary The retina has three classes of cone photoreceptors containing blue (short wave)-, green (middle wave)-, or red (long wave)-sensitive photopigments. Retinal cones are used for vision in bright light and for color vision. The photopigments have characteristic absorption maxima with wide regions of overlap. Perception of color results from comparison between the output from the three cone photoreceptors. The high degree of homology between the red and green pigment genes (including introns and intergenic sequences) has predisposed the locus to unequal homologous recombination/gene conversion events. These illegitimate events cause a change in the number of green pigment genes (including their total elimination) and the formation of red–green hybrid genes. The presence of the red and green pigment genes on the X chromosome and their propensity for unequal recombination account for the relatively high frequency of red–green color vision defects among males. This chapter focuses on determining the gross structure, coding sequences, and expression of the red and green pigment genes.

Correlation between Rayleigh match range in protans and deutans and the difference in λmax between hybrid and normal pigments

Certain protans have gene arrays comprised of L-M hybrid genes and one or more normal M-pigment genes, and certain deutans have arrays containing M-L hybrids in addition to normal L pigment genes. We tested the hypothesis that chromatic discrimination depends upon the difference between spectra of the normal and hybrid pigments in the array. We suggested more severe abnormalities in color vision when normal and hybrid pigments had very similar spectra.

Structure-function relationships in human red/green color vision

The relationship between molecular structure of the visual pigment genes and red-green color vision was studied in 126 normal and 63 color-defective males. We found that the great majority of defects in red-green color vision are associated with the formation of 5′R-G hybrid genes (protan series), deletion of the G gene (deutan series), or the formation of 5′R-G hybrid genes (deutan series). Within these two series, however, dichromacy and trichromacy cannot always be predicted from the molecular patterns, particularly among protans. Amino acid residues in exon 5 largely determine whether a hybrid gene will be more R-like or more G-like in phenotype. We observed numerous genetic polymorphisms in the R and G pigment genes of both normal and color-defective subjects. These polymorphisms may account for some, but not all, of the observed variations in color vision phenotypes. A common Ser/Ala polymorphism at position 180 of the R pigment gene was found to be highly correlated with the bimodal distribution of Raleigh matches we observed among 50 color-normal Caucasian males.