Genomics: A new Revolution in Science:

An Introduction to promises and Ethical Considerations by

Genome Alberta

Overview• Genetics/Genomics described• 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

Anti-parallel strands

Anti-parallel strands

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• Collectively, small differences can make a

big difference.• It determines whether you are short or tall,

hair and skin color and• Differences sufficient to make you are

healthy or not

• Women who carry a genetic variation known as BRCA-1 are seven times more likely to get breast cancer

• Persons missing three nucleotides (CTT) at a very specific spot in have Cystic Fibrosis

Genetics - 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

Genetics - Genomics

– Metabolomics– Proteomics– Transcriptomics

Genomics marked the beginning of a new age in biology and medicine

1900

1953

1977

1980

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1990

1994-98

1998

2000

2005

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

Release of Human Genome Project

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

A single base change in a gene or the addition of a single gene

from another source can make a crop herbicide resistant

Understanding traits, in particular diseases, some inherited

diseases results from the change of 1 base in a sequence

A gene can be used to make a specific product, for example

insulin

Scientists study the genome for a variety of reasons.

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

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

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

Sequencing Cost Have been Dramatically Reduced

A.$10,000B.$100C.1$D.1 $cts E. 0.1 $ctsF. 0.001 $ctsG.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.

Calgary Herald. Monday, Feb 12, 2007

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• Supports research in plant, animal and human genomics,

bioinformatics, instrumentation development and bioethics • additional information is available at www.genomalberta.ca

Genome Alberta’s Areas of Interest

NutrigenomicsNutrigenomics

Study of the Link between Study of the Link between our Diet and our Genesour Diet and our Genes

The burden of obesityThe burden of obesity

Cardiovascular disease$20 billion

Diabetes$13 billion

Self esteem? billion

Slide Courtesy David WishartU of A

Food and PhenotypeFood and Phenotype

Same Junk Food Diet - Different Outcomes -- Why?

Slide Courtesy David WishartU of A

Genomics may have the answerGenomics may have the answerC

G

C

T

C

C

C/G polymorphismIn PPAR gamma

C/T polymorphismIn PPAR gamma

No polymorphismIn PPAR gamma

Slide Courtesy David WishartU of A

Metabolomics could have the Metabolomics could have the answer as wellanswer as well Fat challenge

Seru

m o

xy-li

pids

TimeSlide Courtesy David WishartU of A

Food & phenotypeFood & phenotype

• Genomics and metabolomics allows at-risk individuals to be identified before symptoms appear

• Allows lifestyle changes to be made early on (prevention)

• Allows customization of diet and nutrition to match genotype or metabotype (personalized nutrition)

Food and phenotype - 2Food and phenotype - 2

Different Diet - Different Outcomes -- Why?Slide Courtesy David WishartU of A

Genomics may have the answer !Genomics may have the answer !Gut microflora & metagenomics

Slide Courtesy David WishartU of A

Metabolomics may have an answer Metabolomics may have an answer tootoo Diet + metabolism

monitored via urine

Slide Courtesy David WishartU of A

Food & phenotype - 2Food & phenotype - 2

• Genomics and Metabolomics allow detailed characterization of gut microflora and their nutritional or phenotypic consequences

• Allows customization of diet and nutrition to change gut microflora to a “better” type (personalized nutrition)

Environmental Genomics

Metagenomics or Environmental Genomics

Creating Novel Opportunities for Enhanced Recovery and Reduced Environmental Impact in

the Alberta Oil Sands through Metagenomics

Oilsands Environmental Genomics Concept

Oilsands Environmental Genomics Concept

• Describes a new approach to reduce the environmental and improve production and footprint of present and future oil sands operations by harnessing the activity of indigenous microbial communities active in oil sands deposits and tailings ponds

• Sets out a program area based on creation of a microbial genomics resource for the oil sands as a springboard for innovation

Reduction of Green House Gas Emissions and Improved Water

Recycling• Tailings ponds don’t settle and release

methane, a potent greenhouse gas– Manipulation of the indigenous microbial

community could prevent methane release and accelerate settling

Reduced Energy and Water Use, Higher Recovery, More Producible

Reserves

• Pre-treatment of target deposits by fostering biosurfactant production, CO2, reactive intermediates in the indigenous microbial community could “soften” deposits prior to steam injection

Methane Where we Need it!

• Final energy harvest from residual hydrocarbon left in situ after SAGD or other production technologies have been exhausted– Based on in situ biomethanation

• Process active in heavy oil and oil sands formation• Luca Technologies, Colorado, USA has estimated 37

TCF of methane could be produced from Athabasca Oil Sands*

Opportunities Create Challenges

Creation of a Synthetic Organisms• Could solve Energy challenges and address

Global warming• What are the risks?

Mountain Pine Beetle

The Mountain Pine Beetle Epidemic: A Disease System of Three Genomes

HostPine Trees

Bark BeetleFungal PathogensSlide Courtesy Joerg BohlmannU BC

Mountain Pine BeetleProject Deliverables

1. The first complete genome sequence for a tree-killing, bark beetle-associated fungal pathogen.

2. Expressed genome sequences for the MPB and the pine host.

3. Identification of genes that are linked to bark beetle fitness, fungal pathogenicity, and tree resistance.

4. Application of information from (1) - (3) to improve forest pest management practices by making predictive forest management models more accurate, and developing diagnostics for forest pests and diseases.