The Human Genome Project

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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
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History
Human Genome Project

• 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.

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Ahead of schedule
Human Genome Project

• 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.

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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 lt1 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

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Similarity of man and mouse
Human Genome Project

• There is a difference of only a few hundred genes
  between man and mouse.
• We shouldnt 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.

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New insights for coronary disease
Human Genome Project
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
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Finding causative genes
Human Genome Project
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.
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Pathophysiological insight
Human Genome Project
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.
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Systematic approach
Human Genome Project
I think it is going to change medicine the same
way the periodic table changed chemistry. -Eric
Lander
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Too many variants?
Human Genome Project

• 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.

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When will see a major impact?
Human Genome Project

• 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.

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Cancer treatment vs CV treatment
Human Genome Project

• 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.

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Optimism for the future
Human Genome Project
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