MOLECULAR GENETIC STUDIES OF COLOR VISION

Red or green color vision deficiency ("color blindness") is one of the most common genetic variants in the population, affecting up to 10% of males. Recent studies about the molecular genetics of color vision deficiency, suggest that this arises from deletion of the visual pigment genes on the X chromosome or from the presence of fusion genes which code for visual pigments having anomalous wavelengths of absorption. Coupled with the finding that copy number of the green visual pigment gene is polymorphic in the population, these observations would suggest that the visual pigment loci on the X chromosome are a target for recurrent unequal recombination. To study the molecular basis of this genetic variation, we propose to examine the organization of the visual pigment loci in males with normal color vision (trichromats) as well as those who have color vision deficiency. Color vision will be rigorously tested by use of an analytical anomaloscope. Gene mapping studies will be performed by conventional Southern blotting and by field inversion gel electrophoresis. Genes that have been quantified by densitometry of autoradiograms, will have the copy number confirmed by measuring the size of the NotI restriction fragment that contains the entire visual pigment gene complex. The intergenic regions between red and green and between green and green visual pigment genes will be cloned and mapped to determine where they have diverged. We will use these DNA flanking sequences to map the genomes of the other subjects with normal color vision and with gene copy numbers of R:G 1:1 and 1:2 to establish the degree of genetic variability that may exist in these individuals and to identify the sites of recombination that gave rise to the gene copy number polymorphisms. We will establish the gene organization of individuals with visual pigment deficiency and will map potential sites of recombination in individuals with color vision deficiency. These sites will be sequenced to determine whether they have common structural features among themselves or with other "hot spots" of recombination previously identified in the genome. We anticipate that these studies will yield insight into how unequal recombination contributes to the development of genetic defects.