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Scientists to assess effects of multiple copies of genes on disease risk

Jan. 30, 2007 -- Scientists at Washington University School of Medicine in St. Louis and the biotech firm Nimblegen Systems Inc. have successfully tested a technique for identifying newly recognized DNA variations that may influence disease risk.

Rather than focus on errors and alterations in DNA sequence, the new technique highlights variations in the number of copies of a particular gene. Additional copies of a gene may lead to overproduction of that gene's protein, and this may affect both easily identifiable traits such as body size or more difficult-to-discern traits such as cancer risk.

Scientists report in Public Library of Science Genetics that they refined an analysis technique to assess variations in gene copy number in 20 different mouse strains. According to the paper's lead author, this budding area of study is likely to have wide-ranging implications for scientists' understanding of how DNA variations contribute to human health and illness.

"Right now, our results and other early assessments of human and other mammalian genomes are suggesting that about 10 percent of the genome features copy number variations," says Timothy Graubert, M.D., assistant professor of pathology and immunology and of medicine. "That's a huge number. As a percentage of the genome, variations in gene copy number could explain more person-to-person variability than the single-letter changes in the genetic code known as SNPs [single nucleotide polymorphisms]."

Graubert's lab uses human samples and mouse models to study leukemia, cancer that occurs in the bone marrow cells that make blood cells. Using Nimblegen's technique for assessing gene copy number, they identified approximately 80 variations in the number of gene copies in each of the mouse genomes. Graubert will incorporate the results into his lab's search for genetic factors that protect against or increase susceptibility to leukemia.

Much of the analytic work was led by graduate student P
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
30-Jan-2007


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