Transcript Genomics: A new Revolution in Science

Genomics: A new
Revolution in Science:
An Introduction to promises and
Ethical Considerations
Gijs van Rooijen
Chief Scientific Officer
Genome Alberta
Overview
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Genetics, Mendel to Genomics
Genetic Information defined
Genomics and Biotechnology
Genome Alberta
Genome Alberta Projects
• In the 1850’s an Austrian monk Gregory
Mendel started crossing pea varieties
– He used pollen from some plants to carefully
fertilize other plants
– He was able to observe that characteristics are
inherited in a predictable manner.
– He determined that alleles of a single trait segregate
(separate) independently.
– He observed that the alleles for different traits assort
independently.
– This gave rise to a new discipline that we now call
– GENETICS
What is Genomics
• Genetic information is contained with DNA
(deoxyribonucleic acid) and RNA (ribonucleic
acids)
• Each plant, animal or bacteria carries its entire
genetic code inside almost every one of its cells
• Genomics is the discipline that aims to decipher
and understand the entire genetic information
content of an organism
• Genomics marked the beginning of a new age in
biology and medicine
Genomics marked the beginning of
a new age in biology and medicine
Rediscovery of
Mendel's laws helps
establish the science
of genetics
Huntington
disease gene
mapped to
chromosome 4
Sanger and Gilbert derive
methods of sequencing
DNA
1900
1977
1953
Watson and Crick
identify DNA
(the double helix) as
the Chemical basis
of heredity
1983
1980
DNA markers used
to map human
disease genes to
chromosomal
regions
Source: Health Policy Research Bulletin, volume 1 issue2, September 2001
Genetic and
physical
mapping
1994-98
1990
Human Genome
Projects (HPG)
begins-an
international
effort to map and
sequence all the
genes in the
human genome
1998
Working Draft of
the human
genome
sequencing
complete
2000
2005
(or earlier)
DNA markers used
to map human
disease genes to
chromosomal
regions
Gene map
expected to
be complete
25,000
metabolite
Why is it important to know
the sequence of genes?
 A single base change in a gene in a plant or the addition of a
single gene from any other source to this plant can make a crop
herbicide resistant
 Understanding traits, in particular diseases, some inherited
diseases results from the change of 1 base in a sequence
 We can use a gene to make a specific product, for example
insulin
One change in DNA sequence (mutation)
can have a significant effect!
A
601 ACGGTGCCCG CAAAGTGTGG CTAACCCTGA ACCGTGAGGG
B
601 ACGGTGCCCG CAAAGTGTGG ATAACCCTGA ACCGTGAGGG
+ Herbicide
A
B
Simple model of Gene Modification
• DNA cut with endonuclease
• Sticky ends created
Simple model of Gene Modification
• Modified section with similar sticky ends
inserted
• DNA ligase reattaches new components
Biotech Crops
• potential for impact on farm (and biotech
company) income.
• potential impact on the environment
– Reduction of pesticide use
– Allowed environment friendlier farming practices (e.g
zero tilling)
• May be no perceived benefit to the consumer
• questions about long term safety
• different and more controversial approach genetic
engineering
Some Interesting Genome Facts
• Human Genome contains about 3 billion
basepairs
• Corn Genome contains about 2.6 billion
basepairs but…….
• Wheat Genome contains more than 16
billion basepairs
Not all genetic information encodes for
functional molecules or life functions
Some More Interesting Genomics
Facts
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Humans only have 20% more genes than worms
Around 99% of our genes have counterparts in mice
Our genetic overlap with chimpanzees is about 97.5%
The genetic difference between one person and
another is less than 0.1 %
• But because only a few regions of DNA actively
encode life functions, the real difference between one
person and another is only 0.0003 percent
Single Nucleotide Polymorphisms
(SNPs)
• Major discovery of human genome project was
single nucleotide polymorphisms (SNPs): points
in genome where 2 or more alternative alleles are
found in >1% of population
• 93% genes have SNPs
• ~40% will alter an amino acid
• SNPs may have important consequences for
health/disease
SNPs- The International HapMap
Project
• Goal: To develop a haplotype map of the human
genome, the HapMap, which will describe the common
patterns of human DNA sequence variation
• Outcome: Key resource for researchers to use to find
genes affecting health, disease, and responses to drugs
and environmental factors
• Who: Ten centers in Canada, China, Japan, Nigeria, the
United Kingdom, and the United States
• How much: US$ 200M
• When: Start Oct 2002
International Consortium
Completes Map
International Consortium Completes Map Of Human Genetic Variation
New Tool Speeding the Discovery of Genes for Common Diseases
SALT LAKE CITY, Wed., Oct. 26, 2005
- The International HapMap Consortium today published
a comprehensive catalog of human genetic variation, a
landmark achievement that is already accelerating the
search for genes involved in common diseases, such as
asthma, diabetes, cancer and heart disease.
SNPs
• These small differences can make a big difference,
it determines whether you are short or tall, hair and
skin color and…..
These differences are sufficient to make some healthy
and others very sick
– It can determine whether you get cancer or not. Women
who carry a genetic variation known as BRCA-1 are
seven times more likely to get breast cancer
– If you are missing three nucleotides (CTT) at a specific
spot in your genome you have Cystic Fibrosis
Traditional vs Personalized
Medicine
• Traditional medicine
– Educated guess on which treatment might be most
beneficial
• Personalized Medicine
– the use molecular analysis to manage a patient’s
disease by helping physicians and patients choose
the disease management approaches likely to work
best in the context of a patient’s genetic and
environmental profile.
Traditional vs Personalized
Medicine
• Need for Personalized medicine
– Every Year over 106,000 people in the US die
from adverse reaction to correctly prescribed
doses of drugs
– Another 2.2million suffer serious but not deadly
side effects
Goals for Personalized Medicine
• Identify genetic differences between people
that affect drug response
• Develop genetic tests that predict an
individual’s response to a drug
• Tailor medical treatments to the individual
– Increase effectiveness
– Minimize adverse side effects
Wednesday, Oct 19, 2005
Pivotal Herceptin Data in the New England
Journal of Medicine Showed Significant
Improvement in Disease-Free Survival in
Early-Stage HER2-Positive Breast Cancer
-- Interim Analysis of Two Phase III Trials
Showed That Adding Herceptin to Chemotherapy
Reduced the Risk of Breast Cancer Recurrence
by 52 Percent --
Identification of Genetic Susceptibility
to Disease
• Identify genetic differences between people
that predict susceptibility to disease
• Develop genetic tests that predict whether
an individual will develop a particular
disease
• Offer treatment to prevent or delay onset of
disease
Future Research:
Fixing disease at the DNA level
• Identify genetic abnormality that causes
disease
• Introduce new genetic material that corrects
or bypasses the abnormality
– Gene Therapy
• Isolate piece of DNA containing gene with normal
function
• Introduce into gene transfer tool
• Transfer gene into individual with disease
Accumulation of Sequence
Information
Sequencing Cost Have been
Dramatically Reduced
A.$10,000
B.$100
C.1$
D.1 $cts
E. 0.1 $cts
F. 0.001 $cts
G.0.00001 $cts
Some More Interesting Facts
• Human Genome:
– Took 12 years to complete at a cost of
US$3 Billion
• Mouse Genome
– Took 3 years to complete at a cost of US
$300 million
• Bovine Genome
– Took about 1 year at an estimated cost of
US $30 million
Availability of Personal Genetic
Information Poses Challenges
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Privacy
Confidentiality
Discrimination
Psychological Impact
Something to Think About:
• Who should have access to stored genetic
information? Who owns and controls it?
• How can families resolve conflict when some
members want to be tested for a genetic disorder
and others do not?
• Should employers be able to require job
applicants to take genetic tests as a condition for
employment?
• How would you feel if you tested positive for a
genetic disorder. How would you feel if you tested
negative?
Privacy and Confidentiality of
Genetic Test Results
• Clinical test results are normally included in
a person’s medical records, this could have
serious complications
– For example, when applying for medical, life,
or disability insurance, people may be asked to
reveal their medical history.
Genome Alberta
• Independent not-for-profit corporation
• One of the six regional Genome Centers supported by
Genome Canada
• Genome Canada receives its funds from Industry Canada
• Support research in plant, animal and human genomics,
bioinformatics, instrumentation development and bioethics
• Gather together and link the genomics and proteomics
communities in Alberta regionally, nationally and
internationally
• Assist projects in obtaining co-funding
• Manage the projects and the science & technology
platforms related to those projects
Genome Alberta Ongoing Projects
• International Bovine sequencing project (Start
date Aug 1, 2004)
– Tissue selection and fl cDNA library construction
(approx $400k)
• Applied Health Genomics (Start dates Jan 1
2005)
– Building the Metabolomics toolbox ($7.5M)
– Transplant Transcriptome. ($12.2M)
Genome Alberta-led CompIII
Projects/Platform
• Designing Oilseeds for Tomorrow’s Markets
(DOTM)($17.0M)
• Translating Science: Genomics and Health
Systems ($2.6M)
• Four-Dimensional Modeling Of Genetic Disease
Patterns (4.6M)
• An Integrated and Distributed Bioinformatics
CompIII Platform for Genome Canada ($5.0M,
Start date Jan 1, 2006)
Alberta’s Investment in Science
&Technology
Some Examples
• Alberta Heritage Foundation for Medical
Research ($1B endowment)
• Alberta Ingenuity ($500M endowment)
– Alberta Prion Research Institute
• Genome Alberta