Mike Pazin: As difficult as it was to find
all of the information of the genome, to sequence the genome,
this next step of figuring out what all the information is in
the genome is a much more complex problem. We're just
beginning to understand how this works.
Ross Hardison: Our genome is very, very large
and we're trying to figure where the parts of it make a
difference in our lives, in our susceptibility to disease, and
maybe even impact our behaviors in some ways.
Elise Feingold: The fundamental question we're
trying to answer is what does all the genome do.? What are
all the different functional elements.?
Rick Myers: The whole purpose of the ENCODE
project is to try to figure out which base pairs in the human
genome are important. And that's a big question because
there are a lot of base pairs, and the important ones are not
all in one little package, they are spread throughout.
Ewan Birney: And the human genome when
it was finished, were the letters, okay. What ENCODE is saying is,
"Aha, I think this is a word, and this is a word, and this is a word
and this is a word.
Ross Hardison: If we could understand that,
then we could start to figure out who's really likely to come
down with type 2 diabetes, who's likely to get lung cancer, who
should be making changes in their lifestyles to try to
prevent this, who's going to be most responsive to
certain drugs.
Mike Pazin: There's on the order of 5 percent
of the genome, one-twentieth, that you can ascribe function to.
But that still leaves a large fraction of the genome, maybe 95 percent,
that embarrassingly we don't know what it does. And what
ENCODE is able to do, attribute function to a larger
fraction of the genome than we were able to see before.
Rick Myers: A big part of the project is to
try to figure out where all the proteins that interact with DNA
-- where they're bound in a particular cell at a particular
time during a particular process. You basically freeze
the proteins onto the place in the DNA in the nucleus while the
cell's still alive and then analyze it afterwards.
Ross Hardison: You can get antibodies against
those proteins and we can purify out that subset of the genome
that has a special property. We get those molecules, we put them
into the sequencers. Map them back to the genome and figure
out where these particular chemical processes are
happening. This is just amazing.
Elise Feingold: So it really gets you just a
blueprint, where are you landing and what genes are nearby.
what tissues might that be active in, so really it's a starting point.
Mike Pazin: Very little of our genomes are junk.
80 percent of the genome is engaged in at least one biochemical activity.
For a large fraction of the genome, not now 5 percent, but 80 percent of
the genome, we can say that we know that it does something.
Ewin Birney: This metaphor about junk DNA,
it's become, very entrenched. It's been entrenched publicly and
entrenched scientifically. And ENCODE totally challenges
that. We just don't have big, blank, boring bits of the genome.
All the genome is alive at some level.
Peter Good: What ENCODE does is it provides
a general catalogue of how the genome functions, and so what
they can do is, is they can take their disease tissue -- in the
case of a diabetes researcher, it would be a pancreas or a
muscle cell in a diabetes patient -- and they can ask what
genes are expressed, and then they can look to see how genes
are misregulated in these tissues, and then they can start
back to our catalogue and say, okay, what are the elements,
ENCODE elements, in front of these genes?
Ewan Birney: We can take a disease like
Crohn's disease, which is a pretty bad disease of the
gut, and say to the people studying it, "Well, have you
thought about this particular mechanism? Or this?" And
sometimes they have; sometimes it's a bit of surprise. And they say,
oh I am very interested in that. let me go of and have a look.
But we do that comprehensively for hundreds of diseases compare
alongside hundreds of different mechanisms, and that's been
quite exciting.
Ewan Birney: Well there's 2,000 binding
proteins in the genome. We looked at about 100 of those,
116 of those. So there's a long way to go yet. So there's a lot
more of these guys to study.
Mike Pazin: By having that larger store of
information, I think that will accelerate the pace of health
care. The better we understand it, the more of a chance that we
could intervene in the system in a beneficial way.