Genomics: A new Revolution in Science:

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

4. 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

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

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 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

10. 25,000 metabolite

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

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

27. Simple model of Gene Modification • DNA cut with endonuclease • Sticky ends created

28. Simple model of Gene Modification • Modified section with similar sticky ends inserted • DNA ligase reattaches new components

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

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

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 0.0003 percent

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

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

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, 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.

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

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.

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

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, 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 --

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

45. Sequencing Cost Have been Dramatically Reduced • $10,000 • $100 • 1$ • 1 $cts • 0.1 $cts • 0.001 $cts • 0.00001 $cts

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

47. Availability of Personal Genetic Information Poses Challenges • Privacy • Confidentiality • Discrimination • Psychological Impact

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?

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.

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 www.genomalberta.ca