Human Genome Yields Up More Secrets

But Collins and other experts believe the neutral regions may, in fact, be key players in evolution and disease, swinging into action occasionally and triggering either helpful or harmful changes.

"It's like clutter in the attic," Collins said. "It's not the kind of clutter that you would get rid of without consequences, however, because you might need it."

"Most of the time the human genome is operating on the 'first and second floor,' with maybe 5 percent of the genome doing whatever needs to be done in terms of daily activities," Collins added. "But over evolutionary time, a much larger fraction of the genome -- this stuff up in the attic -- becomes important. In fact, it's probably responsible for getting us where we are in terms of [our] complexity. It's still there, waiting for natural selection to call upon it."

ENCODE is also revealing that epigenetics -- factors that modify the function of DNA but don't change its sequence -- are a major player in disease.

For example, a team at the University of Virginia has found that the degree to which DNA is bound within the chromosome's chromatin structure strongly influences whether that gene can express, or produce, a protein.

While smaller studies have hinted at that before, "this genome-wide survey really shows that these factors are beautifully coordinated," lead researcher Dr. Anindya Dutta, a professor of molecular genetics at the university, toldHealthDay. "Portions of the chromosome that are lightly packed are replicated early, and they also have the highest amount of gene expression."

That means that a too-loose or too-tight "packing" can cause changes in how a gene functions, much like a mutation would. The ENCODE survey found that, "in cancer cells, this happens in 20 percent of our genes," Dutta noted.

Indeed, revelations from ENCODE should, in the long run, greatly enhance research into a variety of diseases, the experts said. The findings come on the heels of a major study, released last week inNature, in which British scientists substantially increased the number of genes implicated in such common diseases as bipolar disorder, diabetes, heart disease and rheumatoid arthritis.

In many cases, the new complexity arising from ENCODE means that "it will take us a bit longer to sort out exactly what is the mechanism of disease risk," Collins said. "We will have some work to do to figure out exactly how [a genetic aberration] works and what is the consequence."

The results announced Wednesday, he added, are merely those of a pilot project. "We aim to scale this up in the not-too-distant future and apply these same approaches to the entire human genome," he said.

And, Collins noted, "I think that we are all, regardless of our philosophical perspective, rather awed by what we are seeing."

A host of related articles on the ENCODE project were also published Wednesday in the June issue ofGenome Research.

More information

For more on the human genome, visit the U.S. National Human Genome Research Institute.

SOURCES: June 13, 2007, news conference,Nature, including Francis Collins, M.D., Ph.D., director, U.S. National Human Genome Research Institute, Bethesda, Md., and Ewan Birney, Ph.D., head, genome annotation, European Molecular Biology Laboratory's European Bioinformatics Institute, Hinxton, England; Anindya Dutta, M.D., professor, biochemistry and molecular genetics, University of Virginia, Charlottesville