Discovery of New Genes May Help Asthma Sufferers Breathe Easier
by Rosalind Schrempf
Decreasing the activity of two newly discovered genes could help reduce susceptibility to asthma attacks, suggests a new research finding at the Lawrence Berkeley National Laboratory. The discovery of two genes that contribute to the development of asthma is a breakthrough for the more than 14 million people in the United States who suffer from asthma and other chronic respiratory conditions.
Asthma is a complex genetic condition in which several genes work in concert, ultimately determining an individual's susceptibility to attacks. Because scientists were not looking for a single gene responsible for a disorder, Edward Rubin and Derek Symula of Lawrence Berkeley National Laboratory (LBNL) and their team from the University of California, San Francisco used an unconventional approach for identifying genetic links to a specific disease. Instead of looking at one gene at a time, they introduced 8-10 human genes at a time into the genome of transgenic mice (mice carrying human genes) to examine several genes simultaneously.
 Eddy Rubin and Derek Symula of LBNL's Life Sciences Division are part of the team that discovered two important genes that contribute to asthma. (Photo courtesy of Lawerence Berkeley National Laboratory) |
The scientists knew that one region of the human genome on chromosome 5 tended to be inherited in individuals with asthma, so they began with this region that contains several million base pairs. Their strategy was to subdivide the region into a few large pieces of DNAwith each piece composed of several hundred thousand letters of the genetic alphabet coding for several genesand introduce these DNA pieces into the transgenic mice. They then looked for changes in processes controlled by these genes. Each mouse contained a different segment of the human chromosome, so the team could rapidly sift through 25 genes located in the genetic region where the "asthma suspicious" genes had been localized. They then matched physical features, or phenotypes, of the mice with characteristics seen in human asthmatics to eventually identify interleukin genes IL 4 and IL13 as those responsible for asthma susceptibility in these animals.
While this study was not conducted on humans, evidence exists that supports the role of these interleukins in human asthma susceptibility. Interleukins have long been known to play a role in regulating the immune system and in particular modulating inflammatory response. The team's approach to pursuing asthma genes may be applied in future research into other common complex genetic conditions such as hypertension and obesity.
These research results were reported in the October 1 issue of the journal Nature Genetics. This project was supported by the U.S. Department of Energy's Office of Biological and Environmental Research, and the National Institutes of Health.
Contact: Eddy Rubin, Lawrence Berkeley National Laboratory, emrubin@lbl.gov
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