The long term goal of this research is to understand the molecular biologic basis of vision. The immediate goal of this proposal is to determine the fundamental properties of X-linked genes that encode cone pigments. To that end the specific aims are: 1. To determine (i) the number of visual pigment genes on the X-chromosome, (ii) the number of genes that encode long-wavelength sensitive pigments, and (iii) the spacing and arrangement of genes encoding middle and long wavelength sensitive pigments. 2. To characterize the cone pigments that underlie protanomalous color vision, to determine the structure of the genes that produce protanomalous pigments, and to investigate the genetic mechanisms that give rise to anomalous pigments. A model to explain the molecular genetic basis of red-green human vision formulated by Nathans et al. (Science 232:198-202, 1986) has gained wide acceptance. Key features of this model include that (i) the average number of visual pigment genes on the X-chromosome is approximately three and (ii) all individuals with normal color vision have a single long wavelength sensitive cone pigment gene. However, the available data do no support these and other basic aspects of the Nathans et al. theory. The significance of the research proposed here is that an understanding of the molecular biology of vision must be built from a base of facts about the most fundamental properties of the genes that encode the cone pigments. Theories conceived to explain the individual differences in normal color vision, common color defects, and rarer more debilitating visual defects, as well as the experiments designed to test those theories, will depend critically on knowing the possibilities allowed by the number of pigment genes, the variety of genes producing different pigments, the relative frequencies of those genes and their arrangements. Knowledge of these basic facts can guide the search for understanding of riot only the properties of the cones--their spectral sensitivities and their ratios--that underlie the diversity of human vision, but also of how the circuits for processing visual information arise. The basic features of the X-linked cone pigment genes from males with normal and color defective vision will be investigated by Southern hybridization analysis and genomic DNA will be used in the polymerase chain reaction to amplify segments of the X-linked visual pigment genes for nucleotide sequence analysis. The color vision and visual sensitivity of the subjects will be examined in detail using psychophysical methods and the electroretinogram.
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