Genomics: A new Revolution in Science:

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• Genomics A new Revolution in Science
• An Introduction to promises and Ethical
  Considerations by Genome Alberta

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• Genomics A new Revolution in Science
• This presentation is available
• at
• genomealberta.ca

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Overview

• Genetics, Mendel to Genomics
• Genetic Information defined
• Genomics and Biotechnology
• Genome Alberta
• Genome Alberta Projects

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• In the 1850s 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

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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

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Genomics marked the beginning of a new age in
biology and medicine
Working Draft of the human genome sequencing
complete
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
Genetic and physical mapping
1900
1977
1983
1994-98
2000
2005 (or earlier)
1953
1980
1998
1990
Watson and Crick identify DNA (the double helix)
as the Chemical basis of heredity
DNA markers used to map human disease genes to
chromosomal regions
DNA markers used to map human disease genes to
chromosomal regions
Gene map expected to be complete
Human Genome Projects (HPG) begins-an
international effort to map and sequence all the
genes in the human genome
Source Health Policy Research Bulletin, volume 1
issue2, September 2001
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25,000
metabolite
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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

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One change in DNA sequence (mutation) can have a
significant effect!
601 ACGGTGCCCG
CAAAGTGTGG CTAACCCTGA ACCGTGAGGG 601 ACGGTGCCCG
CAAAGTGTGG ATAACCCTGA ACCGTGAGGG
A
B
Herbicide
A
B
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Simple model of Gene Modification

• DNA cut with endonuclease
• Sticky ends created

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Simple model of Gene Modification

• Modified section with similar sticky ends
  inserted
• DNA ligase reattaches new components

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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

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Some Interesting Genome Facts

• Human Genome contains about 3 billion basepairs
• Corn Genome contains about 2.6 billion basepairs
  
• Wheat Genome contains more than 16 billion
  basepairs
• Not all genetic information encodes for
  functional molecules or life functions

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Some More Interesting Genomics Facts

• 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

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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 gt1 of population
• 93 genes have SNPs
• 40 will alter an amino acid
• SNPs may have important consequences for
  health/disease

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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

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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.
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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

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Traditional vs Personalized Medicine

• Traditional medicine
• Educated guess on which treatment might be most
  beneficial
• Personalized Medicine
• the use molecular analysis to manage a patients
  disease by helping physicians and patients choose
  the disease management approaches likely to work
  best in the context of a patients genetic and
  environmental profile.

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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

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Goals for Personalized Medicine

• Identify genetic differences between people that
  affect drug response
• Develop genetic tests that predict an
  individuals response to a drug
• Tailor medical treatments to the individual
• Increase effectiveness
• Minimize adverse side effects

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• Wednesday, Oct 19, 2005Pivotal 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 --

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Calgary Herald. Monday, Feb 12, 2007
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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

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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

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Accumulation of Sequence Information
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Sequencing Cost Have been Dramatically Reduced

1. 10,000
2. 100
3. 1
4. 1 cts
5. 0.1 cts
6. 0.001 cts
7. 0.00001 cts

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Some More Interesting Facts

• Human Genome
• Took 12 years to complete at a cost of US3
  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

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Availability of Personal Genetic Information
Poses Challenges

• Privacy
• Confidentiality
• Discrimination
• Psychological Impact

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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?

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Privacy and Confidentiality of Genetic Test
Results

• Clinical test results are normally included in a
  persons 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.

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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
• Much more information is available at
  www.genomalberta.ca