Toxicology Goes Genomic

All-American gene. This "visual genotype" shows how the breast cancer gene BRCA1 varies in 90 people representing the U.S. population.

Environmental health researchers reached a milestone in genomics last week, completing the first phase of an ambitious project to explore how Americans vary genetically in their response to environmental toxins. The data will give toxicologists and other scientists a jump-start in figuring out individual susceptibility to diseases triggered by pollutants, diet, and other environmental factors.

The Environmental Genome Project (EGP) set out 6 years ago to sequence a set of genes that seemed involved in environmentally related diseases. EGP scientists wanted to determine how these genes vary from person to person and whether those changes are associated with susceptibility to disease. It planned to do so by first "resequencing" these genes in DNA samples from a cross-section of the U.S. population, looking for single-base mutations known as SNPs. Initially, some experts were skeptical, but sequencing costs have dropped, and genome researchers have recognized that SNPs occur in patterns that can make them simpler to relate to disease.

Last week, the National Institute of Environmental Health Sciences (NIEHS) in North Carolina, which sponsors the project, announced it has produced a catalog of variation in 200-and-counting genes involved in everything from detoxifying pesticides to metabolizing hormones. Using a set of DNA samples from NIH from 90 individuals, sequencer Debbie Nickerson's group at the University of Washington, Seattle, has now found 17,000 SNPs, about the number expected.

Hundreds of users--from academic scientists to drug companies--are already using the EGP's SNPs database, Nickerson says. Martyn Smith of the University of California, Berkeley, for example, had noticed that workers who don't consume enough folate are prone to developing leukemia from benzene exposure. He suspected that genes for metabolizing folate could also play a role in leukemia in the general population; indeed, he has found that leukemia patients tend to lack certain SNPs in folate genes that are present in healthy people.

Over the next few years, the EGP plans to analyze some 350 more genes involved in other pathways, including signal transduction and apoptosis. NIEHS is also funding related animal and population studies for a total EGP budget of $33 million a year. The ultimate goal is to help people make lifestyle changes to lower their risk and also reduce guesswork involved in setting safe levels of chemicals, says Ken Olden, director of NIEHS.

Related site
The Environmental Genome Project
The EGP's SNPs database

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