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Study: Genome-wide scanning unravels complex birth defect

Researchers from the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins have successfully used genome scanning technology to search through thousands of DNA bits, from every chromosome, to identify two genes that cause an inherited intestinal disorder by working together.

The work is believed to be the first published evidence that genome-wide scanning, using conventional genetic markers and so-called "gene chips," can, in one shot, reveal the underpinnings of diseases caused by multiple genes, say the researchers, whose report appears in the current advance online version of Nature Genetics.

Complex disorders probably result from genetic mutations that create only subtle changes in their proteins' functions. Individually, these changes don't cause symptoms, but in combination they could help explain the occurrence and variability of complex diseases, according to first author Minerva Carrasquillo, Ph.D.

Because of this subtlety, gene hunters have found it difficult to get a single "snapshot" of all the genes that may be involved in these diseases. In the last 10 years, it's been relatively easy only to find the genetic causes of single-gene diseases, such as cystic fibrosis, or one gene at a time for genetically complex diseases.

"In complex diseases like diabetes and heart disease, the genes involved are probably scattered throughout the genome, so you need to be able to look at the whole genome at once and process all that data," says Aravinda Chakravarti, Ph.D., director of the McKusick-Nathans Institute of Genetic Medicine. "Fortunately, the technology now exists to get this done."

Studying the inherited bowel disorder known as Hirschsprung disease, the Hopkins scientists began years ago by looking for single genes, but quickly realized that no one gene could explain the condition completely, says Carrasquillo, a postdoctoral fellow in the McKusick-Nathans Institute.

Already linked to mutations
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
26-Sep-2002


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