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Researchers substitute whole chromosomes to speed the search for genes in common diseases

Medical researchers know that most common human diseases, such as hypertension and diabetes, have a large genetic component. Many genes, interacting with the environment, contribute to these diseases. For researchers, a major challenge is finding all the genes involved with a particular disease.

Researchers from Case Western Reserve University School of Medicine, the Whitehead Institute for Biomedical Research, and Baylor College of Medicine have developed a new method that they believe will revolutionize the search for these genes. In a new research paper, they report that by swapping one chromosome at a time in mice, they can more simply, yet thoroughly, detect the locations of genes involved with complex medical conditions. Their study appears in the April 16 issue of the journal Science, and was posted earlier on the Web site, Science Express.

Through breeding two mouse strains, called AJ and B6, they substituted each chromosome in B6 with one from AJ. They tracked the substitutions through molecular labels marking the ends of each chromosome. The resulting strains are called Chromosome Substitution Strains (CCSs). They developed 22 CSSs of mice, one for each of the 21 chromosomes (including the two sex chromosomes), plus a strain with substituted mitochondria.

They put theory into practice by searching the mice for genetic factors involved with 53 complex traits, related to cholesterol/lipid levels, diet-induced obesity, anxiety and amino acids. By holding everything constant except one chromosome, the researchers could then ask if there were anything on that chromosome causing a change in the mouse. If something did change, it allowed the researchers to know that at least one gene related to the disease was located on that chromosome.

For diet-induced obesity, they found 17 locations compared with past studies by others identifying only two to four genes. In lipids (sitosterol and campesterol, linked with hear
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Contact: George Stamatis
George.Stamatis@case.edu
216-368-3635
Case Western Reserve University
15-Apr-2004


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