Genetic-Environmental Links to Diseases Decoded

By J.R. Pegg

WASHINGTON, DC, April 18, 2003 (ENS) - Scientists have reached a key milestone in identifying which human genes can increase an individual's susceptibility to environmentally linked diseases.

Researchers with the Environmental Genome Project say that they have completed the first phase of the project, and have resequenced and cataloged 200 environmentally responsive genes, identifying links to vascular disease, leukemia and other ailments.

This work sets the stage for researchers to aggressively study the possible links between environmental exposure, human genes and disease development, according to Dr. Kenneth Olden, director of the U.S. National Institute for Environmental Health Sciences (NIEHS), which is spearheading the Environmental Genome Project.

"Gene-environment interactions contribute to many of the most common diseases affecting Americans," Olden said at a press briefing Wednesday that marked the completion of the project's first phase. "The Environmental Genome Project has enabled the health science community to take a major step forward in understanding and potentially preventing environmentally induced disease in susceptible individuals," Olsen said.

The project is an offshoot of the recently completed Human Genome Project. (Photo courtesy National Institute of General Medical Sciences (NIGMS))

The sequence of the human genome has 2.91 billion base pairs and approximately 35,000 genes.

Only a few, relatively rare, diseases are caused by defects in a single gene, and scientists have come to believe that it is the interaction between human genes and environmental exposures that sets the stage for the majority of disease development.

Timing is the third factor thought to play a role in disease development - children, for example, are often found to be more susceptible to exposures.

Environmental exposures are not just pollutants and industrial byproducts, they include diet, pharmaceuticals, infectious organisms and natural compounds.

If researchers can identify how environmental exposures act in concert with particular genetic susceptibilities, they will have the ability to better target treatments and outline specific disease risks.

Scientists hope a better understanding of the links between genetic variation and environmental exposure will lead to better treatment of disease and improved identification of those at risk. (Photo courtesy NIGMS)

The first, and now completed phase, of the project has focused on the polymorphic variants in a spectrum of 200 genes from some 1,000 individuals of various ethnic backgrounds. In particular, researchers have honed in on genes that regulate DNA repair and the cell cycle.

During this first phase of the project, NIEHS has also developed a publicly accessible database of human DNA variation and established a program to develop mouse models for functional analysis of human environmentally associated disease genes.

And it has initiated studies of human haplotypes, which are a set of closely linked genetic markers present on one chromosome that tend to be inherited together.

The governmental health institute is also investigating the ethical, legal and social issues related to Environmental Genome Project research and the development of technology and informatics to support the project.

National Institute for Environmental Health Sciences Director Kenneth Olden has been driving force behind the Environmental Genome Project. (Photo courtesy National Institute for Environmental Health Sciences)

Having identified a specific gene involved in the disease process, researchers can now highlight a specific set of DNA pathways to target for more effective therapies, Olden explained.

"That the polymorphism occurs similarly in black and white Americans, although blacks experience higher rates of death and illness, indicates the complex nature of gene-environment interactions and the need for further research," Olden said.

The second phase of the project will include polymorphism discovery in genes regulating metabolism, signal transduction, and apoptosis, which is often described as programmed cell death.

Olden said researchers expect to sequence more than 350 other genes identified by the scientific community as having possible roles in environmentally linked diseases.

More genes may be added over time, Olden said.

"These results and case studies illustrate how the Environmental Genome Project will lead to improved disease prevention and health management," Olden said.

"We have great hope about our ability to map environmental factors in disease."