Patterns of expression of the X -chromosome photopigment genes and implications for normal and defective color vision

Deutan color vision defects are caused by the lack of a contribution from one of the three spectrally sensitive classes of cone photoreceptor. People who are deutan color blind lack middle wavelength (M) cone function and retain function of the long wavelength sensitive (L) and short wavelength sensitive (S) cone photoreceptors. The L and the M photopigment genes are highly homologous and occur in a tandem array on the X-chromosome. These genes have therefore been subject to numerous unequal recombination events that have led to gene duplications and deletions. A known cause of deutan color blindness is the loss of the M photopigment genes. However, most people who are deutan have genes the encode the M photopigment. For these people the cause of color blindness has remained unknown. Through the work in this thesis, a deleterious mutation was found within the M photopigment genes of two deutan subjects that accounts for the lack of M cone function in these individuals. In addition, in cases where a deleterious mutation was not apparent, individuals were found to have a gene array that contained two L genes and the M gene was positioned last. Position of an L or M gene last within a gene array that contained three genes was correlated with an absence of expression derived from that gene. These experiments led to appreciation for the importance of the structure of the photopigment gene array itself in determining the expression pattern of the L and M genes. The hypothesis that cis-acting factors within the gene array control variation in L versus M photopigment gene expression across the population was then tested within the female retina. Strong evidence was found in favor of factors that occur within the photopigment gene array determining the ratio of expression of the L and M genes. Through the analysis of photopigment gene expression in the female retina, the size of the X-chromosome inactivation patches was estimated for the cone photoreceptor mosaic.