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Genes & Medicine: How DNA is Improving Your Health U3A Mountford, June 2004 Dr Martin Kennedy Department of Pathology Christchurch School of Medicine &

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Presentation on theme: "Genes & Medicine: How DNA is Improving Your Health U3A Mountford, June 2004 Dr Martin Kennedy Department of Pathology Christchurch School of Medicine &"— Presentation transcript:

1 Genes & Medicine: How DNA is Improving Your Health U3A Mountford, June 2004 Dr Martin Kennedy Department of Pathology Christchurch School of Medicine & Health Sciences University of Otago

2 What this talk is not about No, I’m not the waiter. I’m the genetic engineer. How would you like your lamb?

3 What this talk is about: Why is genetics important? Disease genes –inherited disease –complex diseases The human genome project Genetically modified animals Treating disease –finding new drugs –tailored drug treatment –gene therapy

4 Conquering disease Recognition and naming Observation and measurement Understanding of aetiology/pathology Understanding of molecular mechanisms Development of treatments & preventative strategies

5 DNA, chromosomes & genes

6 Chromosome structure

7 Why is recombinant DNA needed?

8 Recombinant DNA (GM)

9 1980 Run for the hills - the recombinant DNA has escaped!

10 1978

11 Why try to understand genes? To provide a window on the disease process Diagnostic or prognostic markers Drug targets Prediction/prevention The vast majority of our knowledge about human genes comes via genetic modification techniques

12 Genetics contributes to most disease Genetics Environment cystic fibrosis Genetics Environment AIDS adult onset diabetes Genetics Environment

13 Genetics contributes to most disease Genetics Environment cystic fibrosis Genetics Environment AIDS Genetics Environment depression

14 Genetics contributes to most disease Genetics Environment cystic fibrosis Genetics Environment AIDS Genetics Environment coronary artery disease

15 Genetic disease Mendelian disease –one gene –genes are causative –genetic mutations –environmental influences eg CF, PKU, haemochromatosis

16 Genetic disease Complex disease –polygenic –genes confer susceptibility or risk –genetic variants (polymorphisms) –environmental influences eg Diabetes, IBD, CAD, autism, anorexia, coeliac disease, Alzheimer’s, asthma, bipolar disorder

17 Genetic disease Congenital disorders –loss or gain of genes –usually sporadic eg Down’s, Williams, PWS

18 Cancer All cancer is caused by damage to genes Damage to several or many genes is required to initiate and progress cancer Some cancers display an inherited susceptibility

19 The human genome project

20 The Human Genome “This scaffold has been handed down to us from our ancestors, and through it we are connected to all other life on earth.” Svante Pääbo, 2001

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25 Molecular characterization of Mendelian diseases

26 Understanding major disease Alzheimer’s DiseaseThird leading cause of death AsthmaAffects 150 million people worldwide Breast cancerAccounts for 20% of female deaths Heart diseaseThe world’s biggest killer Migraine1.4 billion attacks worldwide each year DepressionRanked 4th in W.H.O. global burden of disease analysis

27 Isolation of “susceptibility genes” Korstanje & Paigen 2002, Nature genetics 31, 236-7

28 Major outcomes of HGP Discovery of: –causative genes in Mendelian disorders –susceptibility genes in complex disease Understanding of human history Improved: –drug design –drug treatment –disease management

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30 Microbial genomes

31 Completed microbial genomes 165 Bacteria including: –Yersinia pestis –Helicobacter pylori –Haemophilus influenzae 1790 Viruses including: –SARS –HIV –Several herpes viruses –Several papilloma viruses –Several influenza viruses –Polio

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33 Transgenic organism A plant, animal or microbe that has incorporated, in its own genome, genetic material from another organism.

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35 Transgenic mice Adding genes “Conventional” transgenics (developed early 1980s) Subtracting genes “Knockouts” (developed late 1980’s)

36 Why? Transgenic animals Understanding gene function Modelling diseases “Bioreactors” for vaccines, drugs, etc

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38 Nature Genetics, 2000 Approximately 280 research papers. Of these, 80 (28%) directly focused on GM mice: Cancer:11 Cardiovascular disease:7 Development:15 Neurological or behavioural:11 Reproduction:7 Obesity and diabetes:7 Vision or hearing:7 Technology development: 9 –(including two large scale international programs that generated and screened 40,000 mice, producing 747 new mutants) Others:6

39 DNA and the treatment of disease

40 GE and drug development Identification of new drug targets Production of drugs Structure aided drug design Pharmacogenetics

41 The study of genetic variation underlying differential responses to drugs

42 Adverse drug effects

43 Why pharmacogenetics? Prediction of adverse drug reactions –100,000 deaths annually and 2 million hospitalizations (USA alone) More appropriate prescribing Medicines targeted for specific genotypes Rescue “failed” drugs Making better use of existing drugs

44 Antidepressant treatment of depression

45 Bronchodilators treatment of asthma

46 Inflammatory Bowel Disease

47 Pharmacogenomics

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50 DNA is a potentially powerful drug

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54 Brave new world?

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56 Where is GM in medicine taking us? Better understanding of mammalian biology Better understanding of disease Improved ability to predict disease Improved ability to diagnose disease Improved ability to control disease –safer, more specific drugs –gene guided management –gene therapy

57 Controls and constraints

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