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

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

3. Overview Genetics, Mendel to Genomics Genetic Information defined
Genomics and Biotechnology
Genome Alberta
Genome Alberta Projects
A more detailed breakdown of the organization and curricular fit of this presentation is available on additional documentation.

4. This gave rise to a new discipline that we now call
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
The assumption is that Mendelian Genetics has already been presented prior to this section related to molecular genetics. This slide is presented as a review of Mendelian and segue into molecular.

5. 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
The new science of genomics is defined.

6. 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
2000
2005
(or earlier)
1953
1980
1990
1998
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
The Human Genome Project represents a milestone in that it ushered in a comprehensive plan to map the entire genome sequence. Prior efforts often had individual labs working on smaller sections of specific interest. Cooperation greatly reduced the costs of sequencing and access to the entire information has led to many new research areas not available prior to this.
Source: Health Policy Research Bulletin, volume 1 issue2, September 2001

7. The goals of the Human Genome Project were to identify all of our genes, sequence our entire 3 billion nucleotide genome and store all the information in a massive database that is available to the public.

8. The Human Genome Project was a global effort
The Human Genome Project was a global effort. Anonymous DNA samples were sent to facilities around the world where researchers mapped, sequenced and analyzed the samples. The information they collected was sent to a central database, where it serves as an incredible resource for human genetics researchers.

9. Scientists are busily sequencing the genomes of animals as well
Scientists are busily sequencing the genomes of animals as well. They select which genomes to sequence based on many factors. Take dogs for example. Dogs share many diseases with humans, live in the same environments as people, come in wildly diverse breeds and often have well-documented pedigrees. Different dog breeds are being sequenced such as the poodle and the boxer. Genome Alberta and the University of Alberta have been involved with the sequencing of the Bos taurus (cow).

10. What makes this slide different of significance is that it shows not only the result of translation to a specific protein, but that in some cases genes can affect the the way to metabolites are produced by the cell.
Also of significance, the estimated number of genes that code for proteins has been greatly reduced since the discovery that many proteins undergo post-translational modification.
25,000
metabolite

11. Use this slide to describe more details about the structure of DNA
Use this slide to describe more details about the structure of DNA. A major contribution of the Watson-Crick model for DNA when proposed in 1953 was that it predicted a mechanism to move genetic information from one generation to the next, one cell to daughter cells, and for the information to be used by the cell. “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material”. By providing a mechanism for copying of genetic information, a scientific revolution began leading to, molecular biology, manipulation of DNA for genetic engineering and medical research, and ultimately to the human genome project.

12. DNA is made up of four building blocks
DNA is made up of four building blocks. The nucleotides adenine (A), thymine (T), cytosine (C) and guanine (G).

13. The building blocks make up the DNA helix
The building blocks make up the DNA helix. DNA is normally a double stranded molecule forming a helical spiral.

14. The building blocks that make up DNA are arranged in long strands, called a sequence, that makes up the DNA code. When scientists sequence a gene, they are determining this order. Adenine (A) on one strand binds with Thymine (T) on the other. Likewise, Cytosine (C) binds with Guanine (G). One strand is called the template, the other strand is the complimentary strand. When we know the sequence of the template, we can determine the sequence of the complimentary strand. We can also determine the sequence of messenger RNA produced, and the sequence of amino acids produced.

15. The DNA molecule is organized into segments called genes.

16. Genes contain the information needed to build proteins which do much of the work in our bodies. Each gene codes for a different type of protein. You may wish to discuss transcription and translation at this point.

17. Proteins are responsible for carrying out specific functions
Proteins are responsible for carrying out specific functions. They might be responsible for breaking down the food we eat, making our muscles contract or keeping our skin tight.

18. The genes that code for particular proteins can be turned on and off
The genes that code for particular proteins can be turned on and off. When a gene is on, that particular protein is being made in the cell. When a gene is off, the protein it codes for isn’t being produced.

19. Every cell in our body contains a copy of the exact same genetic code
Every cell in our body contains a copy of the exact same genetic code. This means that each of our cells contain every gene needed to produce every protein. BUT every cell doesn’t produce every protein - only the proteins needed by the particular cell type are produced.

20. Our body’s ability to turn genes on and off is what allows us to have many different kinds of cells that do different jobs. For example, a nerve cell has some genes turned on and other genes turned off. And a muscle cell has a different set of active and inactive genes.

21. Variations in our genes are not the only thing that make us who we are
Variations in our genes are not the only thing that make us who we are. Environmental effects like how much we exercise, what we eat, who our friends are and exposure to toxins play a big role in shaping our individuality.

22. Complex traits like asthma are influenced by both genes and the environment. For example, there may be genes that make someone more susceptible to asthma or modify the severity of the disease. But environmental factors like smoking and allergens also play a big part in someone’s likelihood of developing asthma.

23. The entire DNA sequence makes up what we call the “human genome”
The entire DNA sequence makes up what we call the “human genome”. The genome is the term used for all of the DNA in a cell which includes 3 billion DNA building blocks, or nucleotides. That’s roughly 200 one-thousand page phone books worth of information in each cell!

24. 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
Scientists study the genome for a variety of reasons. This slide begins a discussion on some applications of the technology.

25. The nucleotide variations present in genes can result in physical differences in the proteins they produce. Shown here, are two variations of a gene. These variants produce protein products that are folded slightly differently in this region. Since the amino acid sequence directed by the DNA sequence influences the three dimensional folding of the protein, and since a change of one amino acid in the biologically active region of the protein, this difference in shape could make the protein variants function differently from one another.

26. 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
A resistant phenotype may be produced with a simple change of one nucleotide in the genetic sequence leading to one different amino acid in the protein leading to herbicide resistance. Shown in this slide is a known sequence change in a protein which binds to the herbicide.

27. Simple model of Gene Modification
DNA cut with endonuclease
Sticky ends created
There are several avenues of research allowing scientists to control the rearrangement of DNA sequences. This includes translocations and recombinant DNA. There are available for students a variety of simple demonstration labs – paper and pencil exercises for this concept.

28. Simple model of Gene Modification
Modified section with similar sticky ends inserted
DNA ligase reattaches new components
This is a very simple model of how a gene is inserted into a DNA sequence. It is interesting to know that all of the enzymes now used for the technology were first discovered by scientists occurring in nature.

29. The adoption rate of biotech crops continues to grow
The adoption rate of biotech crops continues to grow. Interestingly, developing countries were initially slow to adopt the technologies but in recent years the adoption rate in Developing Countries has outpaced the growth in Industrial Countries.

30. 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
There are some interesting issues for discussion on this point. In Europe it is the process which is important and considered for Biotech crops. In North America, the product is under scrutiny. Biotech crops may be produced by selective breeding or by mutagenesis after doses of radiation or chemicals. These methods are acceptable in Europe. In North America, Biotech crops may also be produced by genetic engineering by insertion of selected DNA sequence.

31. 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
Polyploidy is a common condition in plants. Some species of ferns are know to have over 1000 pairs of chromosomes. This must make for interesting complexity in mitosis and meiosis.

32. 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
In very closely related species, the difference in chromosome number and sequences is usually related to fusion or splitting of chromosomes and of inversions of large sections of the DNA sequence.

33. 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
If a change of one nucleotide in a specific location occurs in at least 1% of the population, then it is operationally defined as a SNP. These SNPs are considered to be evolutionarily stable, i.e., not changing in frequency from generation to generation. This is an example of Hardy-Weinberg equilibrium.

34. 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
According to their homepage, “The International HapMap Project is a partnership of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States to develop a public resource that will help researchers find genes associated with human disease and response to pharmaceuticals.”

35. 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, 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.
The goal of the International HapMap Project is to develop a haplotype map of the human genome, the HapMap, which will describe the common patterns of human DNA sequence variation.

36. 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
The genotype of a person describes the set of alleles a person has. This includes all the persons SNP alleles. About 10 million SNPs exist. The closer together they are, the more likely they will be inherited together. This reaffirms our model of crossing over and linked genes. The SNPs in a region of the chromosome are called haplotypes.

37. 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.
The technology is already available in some cases to do a quick genetic test determining haplotypes, and prescribing the appropriate medicine and dose based on the individual genetic information.

38. 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
Under traditional medicine, medicines are prescribed based on population based evidence. There are sometime extreme side effects. Personalized medicine uses an individual’s own genetic information to predict treatments and dosages.

39. 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

40. Wednesday, Oct 19, 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 --
In the past, it was considered a major medical breakthrough if the risk was reduced by 5%. In this study, the risk was reduced by 52%. This was an extremely important announcement for scientists and medical practitioners in the field.

41. Calgary Herald. Monday, Feb 12, 2007

42. 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

43. 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

44. Accumulation of Sequence Information
This points out the significance of research in the short period of time since the Human Genome Project was undertaken.

45. Sequencing Cost Have been Dramatically Reduced
$10,000
$100 1$
1 $cts
0.1 $cts
0.001 $cts
$cts
Notice here that the costs of sequencing have changed dramatically in the similar time period. In October 2006, the X Prize Foundation announced a prize of $10 million award for a cheap way to read a full genome. The previous X prize was for the first private space flight.

46. 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
The cost of “doing the science” is coming down drastically.

47. Availability of Personal Genetic Information Poses Challenges
Privacy
Confidentiality
Discrimination
Psychological Impact
These are some issues for discussion.

48. 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?
Additional issues for discussion. The movie “The Score” examines the issues of how a woman deals with the whether or not to have a genetic test for Huntington’s Disease after the death of her mother. If time permits discussion of such issues is highly recommended. The movie is available for classroom use on request from Genome Alberta.

49. 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.
Issues for discussion.

50. 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
Science and technology research is a very expensive and organized activity. This is an exciting new arena with many career opportunities at varous levels of interest.