Revolution in Science:

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Oct 22, 2013 (3 years and 7 months ago)

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Genomics: A new
Revolution in Science:

An Introduction to promises and
Ethical Considerations



Gijs van Rooijen

Chief Scientific Officer

Genome Alberta

Overview


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







1900

1953

1977

1980

1983

1990

1994
-
98

1998

2000

2005

(or earlier)

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

Human Genome
Projects (HPG)
begins
-
an
international
effort to map and
sequence all the
genes in the
human genome

DNA markers used
to map human
disease genes to
chromosomal
regions

Gene map
expected to
be complete

Sanger and Gilbert derive
methods of sequencing
DNA

Huntington
disease gene
mapped to
chromosome 4

Genetic and
physical
mapping

Working Draft of
the human
genome
sequencing
complete

Rediscovery of
Mendel's laws helps
establish the science
of genetics

Source: Health Policy Research Bulletin, volume 1 issue2, September 2001



25,000

metabolite














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

Why is it important to know

the sequence of genes?


One change in DNA sequence (mutation)


can have a significant effect!




601 ACGGTGCCCG CAAAGTGTGG
C
TAACCCTGA ACCGTGAGGG



601 ACGGTGCCCG CAAAGTGTGG
A
TAACCCTGA ACCGTGAGGG

+ Herbicide

A

B

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


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


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