The long term goal of this research is to understand the molecular genetics of vision based on cone photopigments. To achieve this goal, we must first establish a relationship between color vision phenotype and genotype. This requires a clear, accurate understanding of the genotype. Recent evidence indicates that the structure of the arrays underlying normal color vision are radically different than previously appreciated. Thus, the immediate goal of the work proposed here is to gain understanding of the structure of the X-linked pigment gene array. What are the numbers and rations of pigment genes in individual arrays, how do the numbers vary, and what role do """"""""extra"""""""" pigment genes in play in normal vision and in vision abnormalities? What recombination mechanisms play a role in altering the structure of the array; which alterations are associated with color vision defects and more serious vision disorders? How are individual differences in the amino acids of the opsins related to pigment function; what changes are associated with color vision defects, or other vision disorders? Each of the specific aims of this proposal builds on a different new discovery from our laboratories. Each discovery has far reaching implications for understanding vision based on these genes. 1) We have evidence that some individuals do not have intact middle-wave genes, but instead have incomplete genes. 2) We have evidence that individual differences in the numbers and ratios of genes that underlie normal color vision are far greater than had been imagined. 3) We identified a mutation in the genes underlying protanomalous color vision that does not change the absorption peak of the pigment, yet it alters pigment function to produce the difference between anomalous trichromacy and dichromacy. Toward exploring the implications of these findings the specific aims of our research are: 1) To investigate gene rearrangements among the X- linked visual pigment genes with regard to the frequency of occurrence of incomplete middle- or long-wave genes in normal vision and vision defects, and the genetic mechanisms that produce the deletions. 2) To characterize the basic structure of the X-linked visual pigment gene array with regard tot he number and ration of long- and middle-wave genes in the arrays of observers with normal color vision and those with color vision defects. 3) To characterize athe pigments underlying the color vision defects, protanopia and protanomaly, with regard to spectral sensitivity, optical density, and bleaching and regeneration kinetics, and to explore the relationship between gene sequence differences and these functional differences in encoded pigments. Visual capacities of males with normal and defective color vision will be examined in detail using psychophysical methods and the electroretinogram. The X-linked pigment genes will be investigated using Southern analysis, the polymerase chain reaction,a nd DNA sequence analysis.
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