In a blizzard of more than 30 scientific papers published today in multiple basic scientific journals, an international research collaboration has flung open the door of the “wiring closet” of human cells–exposing at least four million gene switches that can both flick our genes on and off, and, like an electric outlet dimmer, work together in minute adjustments to turn genes up or down.
Scientists had originally assumed that only 3% of DNA was active in directing cell functions through the genes, with the other 97% of the human genome nicknamed “junk DNA” or DNA “dark matter.”
“We now know that this conclusion was wrong,” said Eric D. Green, M.D., Ph.D. , director of the National Human Genome Research Institute (NHGRI), a part of the National Institutes of Health.
Understanding the other 97% of DNA will help scientists understand how both genetics and environmental exposures can cause diseases—from lupus to heart disease to cancer—to appear, even in one identical twin but not the other.
ENCODE (the Encyclopedia of DNA Elements) is a nine-year effort involving hundreds of researchers across the U.S., United Kingdom, Spain, Singapore and Japan performing more than 1,600 sets of standardized experiments, with the help of the equivalent of 300 years of lightning-fast computer analyses on more than 15 trillion bytes of raw data, and biochemical technology that didn’t exist five years ago.
Today, the U.S.-funded project simultaneously published the findings of 9 years of work in a series of scientific papers, including one main integrative paper and five others in Nature; 18 in Genome Research; six in Genome Biology; and other affiliated papers in Science, Cell, and other scientific journals.
“This is a paradigm shift in terms of how we look at the genetic basis for disease,” wrote senior author Dr. John Stamatoyannopoulos, an associate professor in the departments of genome sciences and medicine at the University of Washington in Seattle. With diseases, “it’s not necessarily the gene but probably a network of genes that are working together,” and these “switches” or “regulatory” DNA orchestrate entire networks, Stamatoyannopoulos explained.
”I think it’s going to change considerably how people use the genome to identify targets for pharmaceuticals,” he added. The researchers also found that many seemingly different diseases such as Crohn’s and lupus may actually share some regulatory genes. That means that a specific treatment might work in several different subtypes of diseases.
“It’s Google Maps,” Eric Lander, president of the Broad Institute–a joint research endeavor of Harvard and the Massachusetts Institute of Technology–told The New York Times science reporter Gina Kolata. The Human Genome Project, which determined the entire sequence of human DNA, “was like getting a picture of Earth from space,” he said. “It doesn’t tell you where the roads are, it doesn’t tell you what traffic is like at what time of the day, it doesn’t tell you where the good restaurants are, or the hospitals or the cities or the rivers.”
What it means for understanding cancer
The discoveries also can reveal which genetic changes are important in cancer, and why. “These papers are very significant,” said Dr. Mark A. Rubin, a cancer genomics researcher at Weill Cornell Medical College. Continuing the Google Maps analogy, Rubin explained: “Now you can follow the roads and see the traffic circulation. That’s exactly the same way we will use these data in cancer research.” ENCODE results, he said, will help provide a road map with traffic patterns for alternate ways to go after cancer genes.
Sources: National Human Genome Research Institute press release; NIH News Sept. 5 2012 ; AAAS Science Now ; Sept. 5 2012 New York Times .