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Last Updated: Nov 17th, 2006 - 22:35:04

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Latest Research : Ophthalmology : Retina : ARMD

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Gene for age-related macular degeneration discovered
Mar 10, 2005, 02:26, Reviewed by: Dr.

"This is the first study to identify a common variant of the specific gene being associated with AMD. Caucasian AMD patients are at least four times more likely to have one particular alteration in the CFH gene that produces a different form of the CFH protein compared to individuals without the disease."

 
Researchers at Yale School of Medicine have identified a gene for age-related macular degeneration (AMD) on a region of chromosome 1, leading the way for targeted treatment for this widespread eye disease that causes blindness in millions of people.

The study, led by Josephine Hoh, assistant professor in the Department of Epidemiology and Public Health (EPH) at Yale School of Medicine, will be published online in the March 10 issue of Science Express. Hoh and colleagues from Yale, Rockefeller University and the National Eye Institute, used a highly interdisciplinary approach to conclude that the gene for a substance known as complement factor H (CFH) on chromosome 1 is associated with AMD.

"This is the first study to identify a common variant of the specific gene being associated with AMD," said Hoh. "Caucasian AMD patients are at least four times more likely to have one particular alteration in the CFH gene that produces a different form of the CFH protein compared to individuals without the disease."

AMD is a debilitating eye disease affecting about 15 million people in the United States. It destroys vision by attacking an area of the retina called the macula, particularly in people age 60 or older. The macula is the most sensitive region of the retina, enabling fine-detail vision, reading, driving and leisure tasks such as playing sports and watching movies and television. As part of the normal aging process, yellowish waste deposits called drusen accumulate around the macula, but in individuals with AMD, the drusen are larger and more numerous, killing cells necessary for the nourishment of adjacent retinal photoreceptor cells. As these photoreceptors die in and around the macula, central vision is lost. Peripheral vision is not impaired by AMD.

There are two forms of AMD, the more common "dry" form and the less common "wet" form. The wet form can rapidly lead to blindness, while the dry form progresses more slowly. Both are associated with the same variant in the CFH gene.

Hoh and her team used new genetic analysis and microscopic imaging technologies to find the genetic variant of the AMD gene. "What sets our study apart from previous research is that we used many more genetic markers to find the specific gene and variation," said Hoh. "Past research has involved collecting family data that pinpoint a region on chromosome 1, but failed to find the specific gene. We analyzed the DNA of unrelated patients with AMD and compared their genetic profile to that of AMD-free controls. In this sea of DNA information, we applied computation-intensive, statistical analyses and were able to find the differences between the two groups. Subsequently, the gene association has been confirmed by at least three independent studies with results pending publication."

"This work is not only important for the gene we have found, but also highlights the value in new paradigms for whole genome analysis for chronic diseases," Hoh added. "I believe that in order to find genes responsible for diseases, you have to use a totally different approach, instead of an educated guess. Our findings support greater use of this technique."
 

- Science, Online Publication March 10, 2005.
 

www.yale.edu

 
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Other authors on the study are Caroline Zeiss, Susan T. Mayne, Michael B. Bracken, Colin Barnstable and Shrikant M. Mane of Yale; Robert J. Klein, Richard S. Sackler, M.D., Chad Haynes and Jurg Ott of Rockefeller University; and Alice K. Henning, John Paul San Giovanni, Emily Y. Chew, M.D., and Frederick L. Ferris, M.D. of the National Eye Institute.

The research was supported by a grant from the Raymond and Beverly Sackler Fund for the Arts and Sciences.


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