Download The Human Genome Project Eric Lander PhD

The Human Genome Project
Eric Lander PhD
Director
Whitehead Center for Genome Research
Cambridge, MA
Eric Topol MD
Provost and Chief Academic Officer
Chairman and Professor
Department of Cardiology
Cleveland Clinic
Cleveland, OH
Human Genome Project
History
The Human Genome Project has been
underway for 15 years.
1997-2001 were dedicated to sequencing with
a final intensive push over the last 18 months.
February, 2001: dual publication of the
genome maps, with some 94% of the human
genome now freely available on the web.
Human Genome Project
Ahead of schedule
Every milestone in the project was met ahead
of schedule.
The schedule was a shot in the dark; when the
project started, no one knew how long it would
take.
Human Genome Project
Incomplete
Despite the headlines, the sequence is still
incomplete.
The project will be finished when:
every last gap closed in the sequence
errors are at a rate of <1 in 10,000
Expect most of the gaps to be filled by summer,
2001; another 18 months to tidy up the
sequence
The target date to have everything pristine is
April 23, 2003
Human Genome Project
Similarity of man and mouse
There is a difference of only a few hundred
genes between man and mouse.
We shouldn’t be very surprised since man and
mouse show great homology in physical
systems.
While the large physiological systems are
similar, the details in physiology and drug
reaction are not; small variations in proteins
have large consequences.
Human Genome Project
New insights for coronary disease
Two distinct effects are likely:
more sophisticated population
studies to find causative genes will be
possible
availability of the genome sequence will
allow the detection of gene expression
and proteomic analyses
Human Genome Project
Finding causative genes
A substantial fraction of cardiovascular disease
is heritable, but finding the responsible genes
has been difficult.
We already have identified 1.5 million (out of 4
million) sites of genetic variation in the
genome.
When we have all major genetic variants, we
can test each variant for correlation with CVD.
Human Genome Project
Pathophysiological insight
DNA arrays and proteomic analyses will
become available.
Researchers will look at diseased and healthy
tissue in different circumstances to examine
the RNA and proteins expressed.
This will lead to an explosion of ideas and
hypotheses on the pathophysiology and
treatment of disease.
Human Genome Project
Systematic approach
“I think it is going to change medicine the
same way the periodic table changed
chemistry.”
-Eric Lander
Human Genome Project
Too many variants?
The human population is 5000 generations
removed from a small founding population.
Variants in the genome tend to group together
in ancestral segments up and down the
chromosome, making analysis easier.
The number of segments is probably between
30 and 40,000.
Studies will probably end up only involving
some 100,000 genetic variants.
Human Genome Project
When will see a major impact?
Within the next 3 years, everything should be in
place to begin large studies.
2 or 3 years after that should start netting us
many of the important genes.
A decade out we will have a pretty solid
understanding of etiology, pathophysiology and
an explosion of treatment ideas, not unlike what
has been happening in cancer already.
Human Genome Project
Cancer treatment vs CV treatment
A lot of progress has been made recently in
understanding the genetics and treatment of
certain types of cancers.
It may be more difficult to find therapies for
CVD because in cancer, you just have to kill a
diseased/aberrent cell while CVD requires more
subtlety, since it deals with normal cells and
normal responses.
Human Genome Project
Optimism for the future
“I am extremely optimistic that the ground
work is set now for a real molecular
understanding that I think will then translate
into the clinic.”
-Eric Lander