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Research
U-M scientists narrow search for AMD genes


Scientists at the Kellogg Eye Center, working with colleagues in the School of Public Health (SPH), have significantly narrowed the range of chromosomal locations where they expect to find genes associated with age-related macular degeneration (AMD).
Scientist Anand Swaroop and a colleague in Kellogg's microarray lab. Swaroop and his team have narrowed the range of chromosomal locations where they expect to find genes associated with age-related macular degeneration. (Photo by Philip Dattilo)

In a paper published in the March issue of the American Journal of Human Genetics, Kellogg scientist Anand Swaroop and his team of researchers used genetic scanning techniques to identify regions on five chromosomes where AMD genes are likely to reside. They have identified two new locations and have confirmed three locations previously suggested by other researchers.

Kellogg researchers narrowed the search for AMD-related genes by performing a high-resolution genome scan of all 23 pairs of participants' chromosomes. They used more than 700 DNA markers, placed at relatively close proximity (an average of 5 mega-bases apart), to define smaller regions where they will continue their search for susceptibility genes. Markers are commonly used in genetic research. They are known DNA segments that help define locations and regions on chromosomes.

AMD is a progressive disease that destroys central vision. There is no known cure for the disease, which affects millions of people worldwide. While scientists believe there is a strong genetic component, most believe the cause will be found in the interplay of several genes combined with environmental factors, such as smoking and diet.

Swaroop says this study is significant because it confirms locations that have been suggested by other researchers, noting that cross-validation is important for complex diseases such as AMD. "Our researchers have been able to build on past studies—our own and a handful of others—and now we are ready to begin the search for AMD susceptibility genes in earnest," Swaroop says. "We have identified very specific regions of the genome where we can intensify our research efforts."

Patients were recruited from Kellogg's clinical practice and consisted largely of people who suffer from late-stage AMD. Swaroop says this group is likely to carry a heavier load of genetic susceptibility factors than patients in earlier stages of the disease, and thus would be well suited for genetic investigations. In addition, each of the affected individuals was paired with a sibling or other relative, creating a greater likelihood of studying subjects with similar genetic profiles.

The next step for Kellogg researchers is to use microarray-based methods to identify candidate genes within the newly defined regions, Swaroop says. "We will further narrow the candidate regions using other genetic methods, in addition to performing association studies with candidate genes. The next few years should be very exciting," he says.

Swaroop—who collaborated on the study with Gonçolo Abecasis of SPH—notes that Kellogg is well positioned to conduct genetic investigations because collaboration between clinicians and researchers is encouraged and convenient. Retina Service clinicians, in particular, made important contributions to the study. In addition, Kellogg's Center for Retinal and Macular Degeneration, under Swaroop's direction, has one of the largest patient resources for AMD genetic studies, with 2,114 people representing 1,534 families currently enrolled.

Other U-M and Kellogg study authors include Beverly Yashar, Yu Zhao, Noor Ghiasvand, Sepideh Zareparsi, Kari Branham, Adam Reddick, Edward Trager, Shigeo Yoshida, John Bahling, Elena Flippova, Susan Elner, Mark W. Johnson, Andrew Vine and Julia Richards.

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