Genetics Revolution Arrives

June 13, 2007 -- Researchers today announced they have decoded the first 1% of the human genetic code -- and the results already are rewriting the rules of biology.

The massive, four-year, $42 million effort, organized by the U.S. National Human Genome Research Institute, is called the Encyclopedia of DNA Elements, or ENCODE. It involved 35 researcher groups from 80 organizations scattered across 11 nations.

It's a huge success, says NHGRI Director Francis Collins, MD, PhD. The project builds on the Human Genome Project, which in 2003 finally pieced together the DNA sequences that make up the human genome.

"But the genome is written in a language we are still trying to learn how to understand," Collins said in a news conference. "ENCODE is building an encyclopedia to tell us what functions are encoded in this remarkable 3-billion-letter script. That script ... somehow carries within it all of the instructions necessary to take a single-celled embryo and turn it into the very complex biological entity called a human being."

Collins says that the success of this pilot project means that over the next four years, researchers will undertake a $100 million effort to decode the remaining 99% of the human genome.

The early findings already rewrite the human biology rulebook -- especially the rules about what genes are and what they do. The biggest surprises:

• Human genes aren't discrete boxes of DNA. Instead, DNA from all over the genome contributes to the units of inheritance we call genes.
• It was once thought that all functional genes encode protein molecules, the building blocks of the body. The rest of the DNA was called "junk DNA." Now it turns out that this "junk" is just as important as the rest of the genome.
• Genes, once supposed to have only one specific function, are now shown to have, on average, at least five different functions.
• Very few genes actually code for proteins. The vast majority of genes regulate the function of other genes, telling them when, where, and how they should work.
• Many of our genes are just along for the ride, doing us neither good nor harm. But these "bystander" genes may be the stuff from which future human evolution will be made.

It's all much more complicated than had been supposed, says Michael Snyder, PhD, director of the Yale University Center for Genetics and Proteomics.

"I envision this like a sports car," Snyder said at the news conference. "When you first look at it, it looks pretty, simple, and elegant. But as soon as you start prodding under the hood, you find out how complicated it is."

For medicine, the new findings hold a great deal of promise. Nearly all of the recently discovered genes linked to disease risk turn out to be the regulatory genes.

"This may be a good thing, because there is only a subtle tweaking of a gene in a person with disease," Collins said. "Changing that with a small-molecule drug has a good chance of success. We will have some work to do to figure out how that works, and whether the gene is expressed too high, too low, in the wrong place, and so on."

Finishing the human genome encyclopedia will give medical research an extraordinarily valuable tool, says Ewan Birney, PhD, leader of the Birney Research Group at the European Bioinformatics Institute in Cambridge, England.

"We can now start to say why it is that a certain part of the genome is changing the risk for a certain disease," Birney said at the news conference. "And as we go across the genome, we will be providing researchers with a broader and broader set of annotations to understand how diseases really happen, and therefore get more insight into how to cure them."

The ENCODE Project Consortium reports the findings in the June 14 issue of the journal Nature. Twenty-eight companion papers appear in the June issue of Genome Research.