ARLINGTON, Va., Nov. 18, 2002 – Bioengineers have developed the first computer model that can predict the severity of a disease based on a patient's genes.

Bernhard Palsson, Ph.D., of the University of California, San Diego (UCSD), and his group accurately predicted which of 150 genetic mutations would cause chronic anemia and which would result in a milder form of the relatively common disorder.

"This approach is expected to be very useful for drug discovery and development, and may eventually aid physicians in creating effective treatment plans for individuals if their genotypes are known," Palsson said. A UCSD spin-off company, Genomatica, is exploring clinical applications.

The Human Genome Project has revealed hundreds of thousands of possible ways in which two individuals may differ genetically. These subtle differences can also determine who might become ill with a gene-based disease and how sick they could become.

About 150 variations in the genetic code have been associated with hemolytic anemia. Some variations cause a mild disorder, others the more severe chronic hemolytic anemia.

Because of the vast number of variables involved, it is difficult to match these gene differences with their potential health effects. Most match-ups to date have occurred when a known mutation is observed in a patient with symptoms of the disease.

Palsson's approach, published in the November issue of Genome Research, takes advantage of 30 years of chemistry and biology on metabolism in the red blood cell, one of the body's simplest and most understood cell types. This wealth of information makes it possible to model the inner workings of the blood cell.

The model incorporates all the genes in the cell, the products of each, and the intricate process by which these gene products interact to produce cell functions.

"Once we have this computer model, it is, in principle, a fairly straightforward process to alter a specific DNA sequence, run a simulation on the program, and receive information back about how the defect affects the cell's function," Palsson said.

To date, building computer models of complex biological processes has been a daunting task, Palsson said. But new modeling techniques and faster computers, combined with knowledge from the Genome Project, may make it easier to build such models in the future.

"It will take a few years before these kinds of models will become commonplace for diagnosis and management of disease," Palsson said. "Our research is significant in that we are demonstrating the proof of concept for the first time."

Palsson and Whitaker investigator Sangeeta Bhatia, M.D., Ph.D., of UCSD are completing a textbook on tissue engineering with funding from The Whitaker Foundation.

Contact:
Bernhard Palsson, UCSD
The Genome Research paper
Frank Blanchard, The Whitaker Foundation