Comprehensive Set Of Vision Genes Discovered: Identification Could Help In Diagnosing And Treating Blinding Diseases

Photoreceptors — cones, which are activated by light, and rods, which operate only at night — are susceptible to a wide variety of inherited diseases, such as retinitis pigmentosa and cone-rod dystrophy. The newly identified gene set, which is reported in the November 30 Cell, could lead to the identification of genes which, when mutated, cause these degenerative diseases.

"We've cut down the search for disease genes by 100-fold," said Connie Cepko, HMS professor of genetics and senior author of the study. People at risk for inherited retinal disease – estimated to be one person in 2,000 – could be screened for these mutants. The newly identified genetic data base could lead to new methods for slowing or staying the course of disease once it occurs.

"The more we know about how the genes work, the better we will be able to find ways to treat, and possibly, prevent disease," said Cepko. Information about how the genes work inside photoreceptors — which genes are turned on and when — could even lead to ways to replace dead or damaged cells. "Can we manipulate these genes in such a way to coax stem cells to become photoreceptors?" she said.

A little more than half of the mutant genes for degenerative diseases of the retina had been identified when Cepko, Seth Blackshaw, a postdoctoral fellow in Cepko's lab and lead author of the study, and colleagues began their study. Using a computer program that compares snippets of genetic material taken from mouse retinal tissue with a huge genetic data base from the mouse and human genome project, the researchers identified approximately 300 photoreceptor genes — five times the number that were previously known. Two hundred sixty four of these were newly identified genes. Of these, 241 had homologs in humans.

"This makes photoreceptors the single most well characterized cell type in the body," said Cepko. The data base provides a genetic lantern by which to see the goings on inside photoreceptors. For example, by removing a gene, and hence its protein, one can begin to understand how that protein normally functions in the cell.

While answers are likely to take some time, retinal disease gene-hunters are likely to benefit from the genetic data base immediately. "It is really a boon for human geneticists," said Cepko. "We had all these disease loci and now we have a wonderful collection of candidate disease genes."

The research was funded through the Foundation for Retinal Research and National Institutes of Health.