Macular Degeneration : Macular Degeneration International : The Foundation Fighting Blindness

The hunt for the gene began 10 years ago at Baylor College of Medicine when Dr. Richard Lewis, a specialist at Baylor in hereditary disease of the retina, began to collect blood samples from families with Stargardt's disease. Because MDI had a growing number of families affected by Stargardt’s, it helped to recruit many families for this effort. It was already known that Stargardt's and fundus flavimaculatus are caused by a recessive gene determined by a pair of genes, one from each parent. People affected by a recessive trait like Stargardt's disease must have inherited copies of a defective gene from both parents. The parents, who carry just one copy themselves, are normal.

The Baylor researchers, working with Dr. Mark Leppert, geneticist at the University of Utah, began searching for genetic markers that would occur only in patients and carriers. In 1993, a French group found a marker, mapping the gene to a region on chromosome number one.

Baylor and Utah studies continued to try to pinpoint the exact gene by narrowing the marker. "It's like looking for a buried treasure between two palm trees," says Dr. Lewis. ìWe continue digging from each end going towards the middle to find the treasure.î

A surprising turn of events occurred when Dr. Michael Dean of the National Cancer Institute and his group were studying a family of genes known as ABC transporters. They were not working in the area of ophthalmology at all, but they were looking at this transporter problem and where it occurred in diseases throughout the body. Dean stated that recently they had characterized 21 new members of the ABC Super Family of genes and had begun to assign functions to these genes by determining their map locations and their pattern of expression. Many known ABC genes are involved in inherited human diseases. This suggests that some of these new loci will also encode proteins mutated in specific genetic disorders. Here scientists identified one of the 21 human genes specific to the retina (named ABCR for the retina) and its role in the recessive macular dystrophy.

They knew these transporters code for proteins that bound into cell membranes and function as one-way pumps. Most are exporters, meaning that they pump a single type of molecule out of the cell.

The surprise came when this gene being studied mapped to the precise location that the Baylor and Utah groups had described as the site of the Stargardt's gene. Dr. Lewis and James Lupskii from Baylor, collaborating with Dr. Jeremy Nathans from Johns Hopkins University, went to the prior region that was already mapped and found "this new information turned out to be a direct hit," Dr. Lewis said. "It was exciting to see the direct hit, and that the collaboration of several centers was able to quickly find what would have taken a lot longer without their help," he also stated.

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