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Gene Function Within The Context Of Systems Biology

By combining gene traits with biological functions, Medical College of Wisconsin researchers have made the first global assessment of cardiovascular function in rats.

Their paper is published in the current issue of Science.

"By matching physiological traits of rats with their genetic 'maps,' we hope to link specific clusters of genes to physical characteristics that contribute to cardiovascular diseases, including high blood pressure. With the draft of the human genome available, there is a need to better define gene function in the context of systems biology," explains Howard Jacob, Ph.D., director of the Human and Molecular Genetics Center.

The Medical College team of researchers has already found significant relationships between particular rat chromosomes and physiological traits such as vessel response, lipid levels in the blood, and kidney function -- all of which are important contributors to the cardiovascular system.

The researchers were able to take the genetic infrastructure of the rat genome and study it in context of physiologic functions. As a result of the study, they were able to develop the systems biology of the rat to better understand kidney, vessel and nerve and hormonal functions.

In addition to developing a comprehensive physiological model of the physical, biochemical and physiological makeup of the animal (phenotypes) they have developed tools to visualize the genetic and physiologic models.

These tools are necessary because hypertension, or high blood pressure, is caused by a complex combination of behavioral, physical and genetic components. Medical College researchers are using the recent flood of genetic information initiated by the Human Genome Project to look for the possible roots of the disorder, which affects as many as one in every four American adults.

The project was funded by the Specialized Center of Research (SCOR) in Hypertension at the Medical College through a grant from the National Heart, Lung, and Blood Institute. Allen W. Cowley, Jr. Ph.D., professor and chairman of physiology, is lead investigator of the SCOR grant.

Rats are typically used for this type of study because 90 percent of their gene sequence is identical to that of humans. In addition, researchers can breed rat groups that have uniform genetic backgrounds and study them closely for minute changes due to gene manipulation.

The results of their study are being used for further investigation of cardiovascular traits and their relationships to genetic elements, in the hope that these links will contribute to understanding of hypertension in humans at the gene and physiological level.

The study is a cooperative effort of Dr. Jacob and Medical College colleagues Monika Stoll, Ph.D., former post doctoral fellow; Dr. Cowley; Peter J. Tonellato, Ph.D, assistant professor of physiology; Andrew S. Greene, Ph.D., professor of physiology; Mary L. Kaldunski, analyst and project programmer in physiology; Richard J. Roman, Ph.D., professor of physiology, Pierre Dumas, postdoctoral fellow in physiology and Zhitao Wang, analyst and project programmer in physiology; and Nicholas J. Schork, Ph.D., associate professor of epidemiology and biostatistics, Case Western Reserve University, Ohio. - By Toranj Marphetia


[Contact: Toranj Marphetia ]

26-Nov-2001

 

 

 

 

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