The NHLBI "Grand Opportunity" Exome Sequencing Project

Uploaded by NHLBI on 17.05.2012


WILLER: We're doing science now
that we couldn't even have imagined
three or four years ago.
We're doing science now
that simply wasn't technically possible even one year ago.
SILVERMAN: It opens up whole new biological opportunities,
whole new ways of looking at the disease
that we would not have appreciated before.
KATHIRESAN: it's really the culmination
of a decade of work to get to this point.
And it's been extremely satisfying.
O'DONNELL: The Exome Project really developed
out of the knowledge that cardiovascular disease,
lung disease, and some blood diseases
comprise the leading cause of death in the United States.
It's terribly important that we try to understand
not only the environmental causes but the genetic causes.
We believe that by understanding more about the genome,
we can take ourselves even that much further
towards completely preventing heart disease and stroke,
lowering these risk factors,
preventing lung diseases,
and also predicting those who are going to have the diseases
in the future.
WILLER: We put together
this sort of large team-science approach
that's much stronger
than any unique groups of individuals working alone.
So, rather than waiting five or ten years
for many different scientists to, in a step-wise fashion,
move science forward,
we're moving it forward at incredible speeds.
And so what that means for the average American
is that we'll be much quicker to understand disease
and to identify new drugs
that will hopefully make people live healthier, longer lives.
O'DONNELL: We have top-level genome scientists
who are working to help us understand
what the sequence of the genome means,
statisticians and epidemiologists
who are working to help understand
how populations can be studied,
clinicians, cardiologists, pulmonologists,
general internists, hematologists,
all working together in a remarkable fashion
and bringing together many of the cohorts
that have been assembled
by National Heart, Lung and Blood Institute
to make this one big project
that's really clicking on all cylinders.
SILVERMAN: So the Exome Project is a collaborative effort
between many institutions.
It's led by the University of Washington
and the Broad Institute in Boston.
And it's focusing on a variety
of key heart, lung, and blood diseases.
We were glad that one of the diseases
they decided to focus on was COPD.
So in COPD Gene,
we selected a subset of individuals
who had severe disease at a very early age
and lots of emphysema,
and we compared that to smokers who were older,
who had no emphysema
and who had completely normal lung function.
So by looking at those extremes of the distribution,
we thought we might find genetic factors
that make some people susceptible
and other people resistant to the effects of smoking.
WILLER: I've been involved in the LDL portion
of the Exome Sequencing Project,
and so we're focused on individuals
with extremely high or extremely low LDL cholesterol,
and we're looking at differences in their DNA
to try to understand
which will change their risk of heart attack.
So if we can understand the differences in their DNA
that increase their risk of heart disease,
we might be able to develop much better treatments
to prevent heart attack across the whole population.
KATHIRESAN: Our overall project is trying to understand
what genes cause heart attack in people.
Our approach is to look at individuals
who developed heart attack
and compare them with individuals
who never developed heart attack.
And the specific genetic approach we've taken
is called sequencing.
The human DNA sequence is about three billion letters.
Of these three billion letters,
about 30 million of the letters code for genes,
and this portion of the genome are called exons or the exome.
O'DONNELL: With the new technology,
we can look at the sequence of these exons in the genome,
the protein-coding genes,
and we can really take to another level
our understanding of how genetics
predisposes to diseases.
One of the most exciting aspects of the Exome Sequencing Project
is the fact that we are studying on both men and women
and also multiple ethnic groups.
So, the findings that come out of the Exome Sequencing Project
will be relevant to all segments of the population
of the United States.
Now about two years into the project,
we've already completed sequencing
in over 5,000 of the individuals that we slated for sequencing.
We've begun studies of patients with heart attacks,
with strokes,
patients with high and low blood pressure,
high and low levels of LDL cholesterol,
which is the damaging type of cholesterol,
and also those with high levels of blood sugar
and obese individuals,
as well as a variety of lung diseases.
SILVERMAN: Our goal has been to deposit all of the information
that we're collecting from our volunteers --
their clinical tests, their breathing tests,
their imaging tests, and their genetic tests --
into a central monitor repository
so that in a safe and confidential way
other investigators throughout the U.S.
and throughout the world can get this information
for their own research.
O'DONNELL: Sharing of data
is one of the most important contributions
that will come out of the Exome Sequencing Project.
By putting these data out into the public domain,
there will be many more discoveries
that come out of the data that's been put in there,
not only this year, next year, but for many years to come.
We believe that medicine is moving towards
what we call genomic medicine,
where many of the decisions that are made
by doctors and practitioners are based on information
in the human genome on each patient.
Without conducting studies like the Exome Sequencing Project,
we really won't be able to realize this goal
of genome sequencing and genomic medicine
in any near future time.