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

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 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 percent

Sequencing Cost Have been Dramatically Reduced A.$10,000 B.$100 C.1$ D.1 $cts E.0.1 $cts F $cts G $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

Genome Alberta’s Areas of Interest

Nutrigenomics Study of the Link between our Diet and our Genes

The burden of obesity Cardiovascular disease $20 billion Diabetes $13 billion Self esteem ? billion Slide Courtesy David Wishart U of A

Food and Phenotype Same Junk Food Diet - Different Outcomes -- Why? Slide Courtesy David Wishart U of A

Genomics may have the answer C G C T C C C/G polymorphism In PPAR gamma C/T polymorphism In PPAR gamma No polymorphism In PPAR gamma Slide Courtesy David Wishart U of A

Metabolomics could have the answer as well Fat challenge Serum oxy-lipids Time Slide Courtesy David Wishart U of A

Food & 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 - 2 Different Diet - Different Outcomes -- Why? Slide Courtesy David Wishart U of A

Genomics may have the answer ! Gut microflora & metagenomics Slide Courtesy David Wishart U of A

Metabolomics may have an answer too Diet + metabolism monitored via urine Slide Courtesy David Wishart U of A

Food & 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

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, CO 2, 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 Host Pine Trees Bark Beetle Fungal Pathogens Slide Courtesy Joerg Bohlmann U BC

Mountain Pine Beetle Project 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.