Scientists Unveil 'Google Maps' For Human Genome

Sep 5, 2012
Originally published on September 5, 2012 4:56 pm

Scientists unveiled the results of a massive international project Wednesday that they say debunks the notion that most of our genetic code is made up of so-called junk DNA.

The ENCODE project, which involved hundreds of researchers in dozens of labs, also produced what some scientists are saying is like Google Maps for the human genome.

"We like to think about the ENCODE maps similarly," said Elise Feingold at the National Human Genome Research Institute."It allows researchers to look at the chromosomes and then zoom into genes and even down to individual nucleotides in the human genome in much the same way that someone interested in using Google Maps can do so."

For decades, scientists thought that most of our genetic code was essentially useless — basically filler between our genes. Only a tiny fraction — the part that has genes in it — really mattered, according to this thinking.

"The phrase that was thrown around was junk DNA," said Michael Snyder, a geneticist at Stanford University who participated in the project. "I think all of us would agree that really wasn't a good term because it was simply something that we didn't know what it did."

So in 2003, the National Institutes of Health launched the ENCODE (Encyclopedia of DNA elements) project, at a cost of $288 million. The researchers conducted more than 1,600 experiments to understand what is going on in this supposed genetic wasteland.

The results appear in more than 30 papers published in a slew of leading scientific journals, including Science, Nature and Genome Research.

"So the most amazing thing that we found was that we can ascribe some kind of biochemical activity to 80 percent of the genome. And this really kind of debunks the idea that there's a lot of junk DNA or really if there is any DNA that we would really call junk," NHGRI's Feingold said.

What has been called junk DNA is actually teeming with an intricate web of molecular switches that play crucial roles in regulating genes. The ENCODE project scientists found at least 4 million of these regulatory regions so far.

These switches rev genes up. Calm them down. They orchestrate how the whole complex system works. Scientists have already started to figure out which switches control which genes. And that's uncovered even more surprises. Genes can get instructions from up to dozens of switches. And some of the switches are nowhere near the genes they control.

"Most of the human genome is out there mainly to control the genes," said John Stamatoyannopoulis, a geneticist at the University of Washington School of Medicine, who also participated in the project.

The findings help explain why so many studies have found genetic mutations that appear to be associated with diseases in places where no genes reside. It turns out, these areas contain the molecular switches that, when damaged, are behind the diseases.

"The whole way that we look at the genetic basis of disease is going to change. And it's going to change from this model from trying to look at particular this gene or that gene etc to trying to look at genes operating as a system or a network," Stamatoyannopoulis said

Other scientists hailed the findings as providing crucial new insights. But they warned that any payoff probably won't be seen any time soon. "I think it would be irresponsible and really counterproductive to try to massage this into a situation where you're going to go to the doctor's office in the next year and see these things playing out," said James Evans of the American College of Medical Genetics. "That's not the way science works."

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Scientists drew their first rough map of the human genome back in 2000. But parts of our genetic blueprint are still not well understood. Today, researchers unveiled the results of a massive international project that explored parts of our DNA that are not genes, the pieces in between the genes.

As NPR's Rob Stein explains, the effort has produced some surprising findings.

ROB STEIN, BYLINE: For years, scientists thought that most of our DNA was essentially useless, mostly filler between the genes that carry instructions for everything in our bodies. The conventional wisdom was that only a tiny fraction of DNA, the part that has genes, really mattered. There was even a catchy name for this vast genetic wasteland.

MICHAEL SNYDER: The phrase that was thrown around was junk DNA.

STEIN: That's Michael Snyder, a geneticist at Stanford University.

SNYDER: I think all of us would agree that that really wasn't a good term because it was simply something we didn't know what it did.

STEIN: So in 2003, the National Institutes of Health launched the ENCODE Project. More than 400 scientists in 32 labs around the world scoured this supposed junk DNA. They conducted more than 1,600 experiments to try to understand what was really going on there. Today, they unveiled the results in more than 30 papers being published in a slew of leading scientific journals.

Elise Feingold is with the National Human Genome Research Institute.

ELISE FEINGOLD: So the most amazing thing that we found was that we can ascribe some kind of biochemical activity to 80 percent of the genome. And this really kind of debunks the idea that there's a lot of junk DNA.

STEIN: Instead, this DNA is actually teeming with a web of complex molecular switches, switches that play crucial roles in regulating genes. The scientists have found more than four million of these switches so far.

Here's John Stamatoyannopoulis of the University of Washington.

JOHN STAMATOYANNOPOULIS: Most of the human genome is out there to control the genes. In other words, to sort of have the programming of the genome or sort of its operating system, if you will.

STEIN: These DNA switches rev genes up, shut them down. They orchestrate what makes skin cells skin, brain cells brain, and so forth. They choreograph everything for making individuals who they are.

STAMATOYANNOPOULIS: There's a complicated web of connections that run along the genome that sort of specifies how its operations work.

STEIN: Scientists have already started to figure out which switches control which genes. And that's uncovered even more surprises. Genes can get instructions from dozens of these switches. And some of the switches are nowhere near the genes they control.

Stamatoyannopoulis says an early analysis of some of the data appears to explain some of the mysteries about how mutations in DNA make people sick.

STAMATOYANNOPOULIS: The whole way that we look at the genetic basis of disease is going to change. And it's going to change from this model of trying to look at that gene or this gene, et cetera, to trying to look at genes operating as a system or a network.

STEIN: Other scientists hailed the findings as providing crucial new insights. But they warned that the payoff probably won't happen anytime soon.

James Evans is a geneticist at the American College of Medical Genetics.

JAMES EVANS: I think it would be irresponsible and really counterproductive to try to massage this into a situation where you're going to go to the doctor's office in the next year and see these things playing out. That's not the way science works.

STEIN: It'll take years to sort through the millions of combination of genes and genetic switches to sort it all out. But Elise Feingold at the NIH says the ENCODE Project has provided a kind of genetic Google Map to guide the way.

FEINGOLD: It allows researchers to look at the chromosomes and then zoom in to genes, even down to individual nucleotides in the human genome, in much the same way that anyone using Google Maps can do so.

STEIN: That, Feingold says, would help scientists explore what was once dismissed as a meaningless void in our DNA.

Rob Stein, NPR News. Transcript provided by NPR, Copyright NPR.