The Human Genome Project? in your classroom

1. The Human Genome Project?in your classroom Fiona Cunningham Education Officer the gene CRC CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

2. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

3. The Human Genome Project • Established 1988 • Initiated 1990 • Predicted to revolutionise human medicine: • investigating molecular basis of genetic disease • testing • prevention • new therapies CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

4. DNA • Twisted ladder or DOUBLE HELIX • Rungs of ladder - bases A G C T • Sequence of AT & GC pairs determines proteins structure and function • Alter base sequence - MAY change protein • GOOD, BAD or INDIFFERENT CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

5. First Draft published Feb 2001 First Draft completed June 2000 CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

6. The Map….. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

7. ? Francis Collins, NIH Craig Venter, Celera Genomics The players CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

8. Whose genome was sequenced? • How many individuals? • Public effort (NIH, DOE etc) • 1 (15%) + 1 (70%) + some (the rest) • Could they miss any genes? • Celera’s 5 individuals • all sequenced, aligned • identified polymorphisms, SNPs, where differences occurred CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

9. Sequencing every base….. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

10. Why sequence every base pair? • Maps of the genome are important • Why? • localisation of genes • homologies between species • why else? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

11. Arabidopsis Drosophila Baker’s Yeast Chicken Genome Project? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

12. Has every base pair been sequenced? • No • 3.2Gb estimated size • 84% of the genome • ~30,000 genes • What does it mean? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

13. ~30 000 genes …. • NIH - 31 000, 22 000 listed • Celera - ~26 000 • ~740 non-protein coding RNAs - cell housekeeping (many more not IDd) • Compared to: • yeast 6 000, fly 13 000, worm 18 000, plant 26 000 • Only 30 000 genes: are humans really quite biologically simple? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

14. Human complexity? • Most genes from our evolutionary past • Only ~94 of 1278 protein families specific to vertebrates • Diff between us and worms is the complexity of our proteins: • more domains per protein • greater regulation of transcription & translation CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

15. The future….. • First there was HUGO • Now there is HUPO! • Proteomics: the cash ‘crop’ of research in the future? • Functions and expression patterns of proteins encoded by the genes CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

16. Why genetics for my students? • Will it change anything? • Knowledge of genes role in diseases • Immediately ~ still woke up and had cornflakes the next day • Short term • Long term CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

17. Genes, disease & testing • Over 6000 single gene disorders identified • Many diseases are multifactorial • many genes interact with each other • & with the environment • eg Alzheimer disease, diabetes, CHD, asthma • (many other common diseases may have a genetic component: inherit predisposition or increased risk to develop these) CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

18. Genetics in the 21st century (1) • Genetic testing: • carrier, diagnostic, predictive, predisposition • newborn • prenatal • Risk vs certainty • Uses of this info? • Non-disease traits? • IQ, aggression, height? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

19. Screening programs in Victoria • Newborn screening • PKU, Congenital Hypothyroidism, Cystic fibrosis, (other metabolic conditions?) • Tay Sachs disease • Neurodegenerative disorder, Jewish schools • HAEMscreen (pilot study) • Iron overload disorder - affects adults • Common and preventable • Pilot screening program in workplace CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

20. Genetics in the 21st century (2) • Gene & related therapies • better drug therapies • better environmental modification strategies • cell & cloning technologies • gene therapy • therapeutic • enhancement CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

21. Genetics in the 21st century (3) • pharmacogenomics CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

22. Genetics in the 21st century (4) • Forensic science: genetics is used in • identifying suspects in criminal cases • food contamination testing • paternity testing CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

23. Genetics in the 21st century (4) • Not just medical applications: • GMO’s • food • agriculture • environment • industry • Cloning • nothing really to do with HGP CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

24. Cloning in the 21st century • Reproductive vs therapeutic • Sevorino Antinori et al. • Raelian cult & Clonaid • Can personality be cloned? • Can we live for ever? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

25. Therapeutic cloning • Involves stem cell technology • Stem cells are derived from the inner cell mass of a 1-week-old embryo (blastocyst) • Unlimited, prolonged self-renewal • Can divide and differentiate into any type of body cell (!!!!!) CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

27. Stem cell uses? • Screening of drugs that may cause birth defects • Discovery & study of rare human proteins • Study of early human development • Gene therapy vector • For transplantation of tissues • still problem with rejection from patient CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

29. unethical ES cell lines: tissue for transplantation Human cloning may be ethical? ETHICAL? CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

30. Why the controversy? Deriving stem cells from embryos destroys them! CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

31. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

32. ELSI: Ethical, legal & social issues • Privacy • Confidentiality • Discrimination • Right to know • Right not to know • Family issues • Social issues CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

33. Insurance & Patenting • Health insurance in Aust • Life insurance in Aust • What can be patented? • Gene • gene product • specific drugs which target the gene or gene product CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

34. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

35. Gbenetics in your school? • How can we ensure responsible & ethical use of genetic knowledge & technology? b CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

36. Strategies for the classroom • Don’t start with peas, flies or worms • Start with human stories • Encourage students to express their views (try not to be directive) • But also to give solid argument & reasons for these views • Encourage them to think beyond their own personal field: • legal, economic, social, religious views, family, community CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

37. Equipping your students: • An understanding of genetics • Skills to • ethically analyse genetic technologies • critically read and evaluate media reports • actively seek out appropriate information - • www, institutes, medical & research institutes CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

38. Biomedical ethics: a simple framework • Maximising benefits • (beneficence) • Minimising harm • (non-maleficence) • Autonomy • includes individual rights and freedom of choice • Justice • fairness, equality, non-discrimination CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

39. Equipping you: • Be informed • Professional development • Critically read newspaper articles • Actively seek out appropriate news and documentaries • Participate in debate CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

40. Equipping you: • Integration into other areas of the curriculum • Biology/science • English, philosophy, religion & society, physical education, legal studies etc • Resources: • www, geneTHINK, geneTALK etc CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

41. Figure 5. An example of a worksheet and teacher notes. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

42. GENE Think 2000 CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

43. GENETalk 1General GeneticsNovember 2000 MCRI Education Unit MaryAnne Aitken Fiona Cunningham Eilís Hughes Sylvia Metcalfe CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

44. SPERM 23 chromosomes in nucleus EGG 23 chromosomes in nucleus fertilised egg (ZYGOTE) 46 chromosomes in nucleus MEIOSIS halves chromosome number MITOSIS Where do our chromosomes come from? Every somatic cell in body has the same 46 chromosomes CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

45. Mother’s Genotype Cc Father’s Genotype Cc Possible Offspring C c C c C C C c C c c c Autosomal recessive pedigree (cont.) Probability of CF = (Prob ofcallele from mother) x(Prob of callele from father) Probability of CF = 1/2 x1/2 = 1/4 CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

46. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

47. The Genethics Challenge “A controversial technology with enormous potential. And our challenge? To fulfil this potential without compromising our ethical ideals.” Ling San Lau, Genethics 2000 winner CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

48. CRC for Discovery of Genes for Common Human Diseases (the gene CRC)

49. The Eutopian Times GENEdreams, a human biotechnology company in Eutopia, has captured the attention of parents-to-be with their offer of ‘Design your own healthy baby!’ after launching a proposal to conduct genetic screening of unborn babies to prospective mothers. This program uses their patented “BABY BODY microchip” that uses DNA microarray technology to screen foetuses between the 10th & 12th week of pregnancy for gene alterations that cause deafness, dwarfism & predisposition to breast & colon cancer. All for a mere cost of Eut$10 000!

50. Civil rights & right-to-life activist groups have been outraged by this proposal, along with disability groups such as the Eutopian Cultural Deaf Foundation & SSPE (Short Statured People of Eutopia). A spokesman from the Eutopian Health Ministry ridiculed the proposal, stating that “all babies are offered newborn screening for treatable genetic conditions such as PKU & cystic fibrosis free of charge. The GENEdreams service preys on the fears of parents & and is unnecessary.” GENEdreams commented “it is the right of every parent to choose whether or not to have a baby with or without a disability and to desire the best possible health outcomes for their children. If most parents decide against having a child with a disability, there will be more money available to help those who are born with a disability.”