Making babies: Genetically Correct

1. Making babies: Genetically Correct Zhi Hua Ran The department of Gastroenterology Ren Ji Hospital

2. A Glossary of Genetics Terms Gene: basic unit of inheritance for all living organisms Genome: Genetic endowment of a species Gene mapping: Determining location of genes on chromosome Gene sequencing: Determining identity of genes from the distinctive order (sequence) of base pairs, such as A-T and G-C Chromosome: Threadlike structure in the nuclei of plant and animal cells; it carries the linearly arranged genetic units (genes)

3. A Glossary of Genetics Terms Nucleic acid: Large, chainlike molecule of phosphric acid, sugar and purine and pyrimidine bases Marker: Gene with a known location on a chromosome Template: Macromolecular model for another macromolecule, as in the synthesis of RNA from a DNA template Transgenic: Organism, such as a mouse, containing experimentally transferred genetic material from another organism, such as mammal Mutation: Abrupt change in the genotype of an organism that is not the result of recombination

4. A Glossary of Genetics Terms Recombination: Formation in offspring of genetic combinations not present in parents Genotype: The genetic constitution of an individual Phenotype: The observable characters of an organism; the result of the way the genes are expressed Genetic defect: Pathological changes that occur by duplication, deletion or rearrangement of DNA Transcription: The process by which RNA is formed from DNA Nucleotide: The structural unit of nucleic acid

5. A Glossary of Genetics Terms RT-PCR: Reverse transcriptase polymerase chain reaction Gene therapy: A technique for correcting defective genes responsible for disease development DNA microarray: An experimental tool for obtaining high-throughput gene expression data Stem cell: have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

6. Milestones of Genetics Discover the double-helix structure of DNA---by James Watson and Francis Crick Create the first recombinant DNA molecule---by Paul Berg Mapping the human genome---The Human Genome Project, completed in 2001

7. Discover the DNA structure 1953---James Watson/Francis Crick Double-helix structure of DNA

8. Biography---James Watson Born in Chicago, April 6, 1928 His father‘s ancestors were originally of English descent His mother‘s father was Scottish-born taylor married to a daughter of Irish immigrants who arrived in the US about 1840 Spent entire boyhood in Chicago

9. Biography---James Watson Study at University of Chicago at 1943 In 1947, received a B.Sc.degree in Zoology During these years, his boyhood interest in bird-watching had matured into a serious desire to learn genetics In 1950, received Ph.D degree in Zoology at Indiana University His Ph.D thesis was a study of the effect of hard X-rays on bacteriophage multiplication

10. Biography---James Watson In the spring of 1951, he change his direction of his research toward the structural chemistry of nucleic acids and proteins Met Crick at 1952, common interest in solving the DNA structure Solved in early March, 1953---the proposal of the complementary double-helical configuration

11. Biography---James Watson 1953~1955 at the California Institute of Technology as Senior Research Fellow in Biology 1956, Assitant Professor, Harvard Biology Department 1958, Associate Professor 1961, Professor 1962, The Nobel Prize in Physiology or Medicine

12. Biography---Francis Crick Born on June 8, 1916 at Northampton, England In 1937, obtained a B.Sc. In Physics at London Started to learn biology in 1937, interrupted by World War Two During the war, he worked as a scientist for the British Admiralty Left the Admiralty in 1947 to study biology

13. Biography---Francis Crick Joined the Medical Research Council Unit since 1949 Restarted in 1950, obtained Ph.D in 1954 Worked out the general theory of X-ray diffraction by a helix 1962, The Nobel Prize in Physiology or Medicine Died at 2004

14. Biography---Paul Berg Born on June 30, 1926, New York Gained early recognition/influence when he delineated the key steps in which DNA produces proteins Best known for his development of a technique for splicing together DNA from different types of organisms. His achievement gave scientists a tool for studying the structure of viral chromosomes and the biochemical basis of human genetic diseases. Awarded the Nobel Prize for Chemistry in 1980

15. The Human Genome Project Began at 1990 Founded by US department of Energy (DOE), US National Institute of Health (NIH) in collaboration with Britains Wellcome trust Draft sequence was published in 2001

16. The Human Genome Project Celera Genomics, a private company based in Maryland, is publishing its findings in Science. A public international effort, led by the United States, is publishing its analysis of the genome in Nature, a British journal. Human have about 30,000 genes Genetic differences between any two people are relatively small

17. The Human Genome Project---more powerful tools Durg development, customizing drugs to individual genetic profiles Earlier diagnosis of disease

18. In Vitro Fertilization---history The technique was developed in the UK by Dr. Patrick Steptoe and Robert Edwards First “test tube“ baby: In UK, Louise Brown (July,1978 Second “test tube“ baby: In India, Kanupriya Agarwal by Dr. Mukhopadhyay (Oct, 1978) The first in US: Elizabeth Carr by Dr. Howard and GS Jones (1981) Since then, IVF has exploded in populatiry, accournts 1% of all birth, 115,000 in total in US

19. In Vitro Fertilization---history 1y The first “test-tube “ baby Louise Brown born in England in July 25, 11:47 PM, 1978 25 y With parents

20. In Vitro Fertilization---history Dr. Patrick Steptoe At birth Oldham General Hospital Dr. Robert Edwards

21. In Vitro Fertilization Phase 1: The first phase consists of stimulating the ovary with hormones injected, in order to cause several eggs to mature Normally, only one egg matures per menstrual cycle, so additional hormones are usually required to prevent the body from negatively to this excess of eggs The last injection given is that of human chorionic gonadotropin (hCG), the hormone normally produced during pregnancy

22. In Vitro Fertilization Phase 2: The second phase, that of egg retrieval, occurs about 34-36 hours after the hCG injection The entire procedure usually takes 8-20 mins

23. In Vitro Fertilization Phase 3: The third phase involves fertilization of the eggs

24. ICSI---Intracytoplasmic sperm injection 3 1 2

25. In Vitro Fertilization Phase 4: Phase four is the actual embryo replacement A pregnancy test usually is done 12-14 days after retrieval 2 Cell embryo 4 Cell embryo 8 Cells embryo

26. Thumbing through the encyclopedia of life Technology often drives science, science drives medicine, and medicine is always pushing society in to ethical corners Dr. Mark Hughes

27. Prenatal Genetic Analysis One of the ethically most problematic applications of genetics If detected in the fetus, are incurable, may lead to selective abortion Prenatal diagnosis of genetic traits typically can only provide information to assist the prospective parents in their decision making whether to carry the pregnancy to term or to terminate it

28. Prenatal Genetic Analysis It requires both a medical indication and informed conset of the parents Parents have a right to refuse medically indicated prenatal diagnosis even if there is a high risk for fetal condition that is incompatible with life There are a few genetic traits (such as gender) are accessible to prenatal diagnosis today but unrelated to health

29. Prenatal Genetic Analysis Prenatal diagnosis is carried out only to give parents and physicians information about the health of the fetus The use of prenatal diagnosis for paternity testing, except in cases of rape or incest, or for gender selection, apart from sex-linked disorders, is not acceptable WHO 1998

30. Prenatal Genetic Analysis Heterozygosity testing for recessive disease could only be attempted for eugenic purposes Gregor Mendel 1822~1884 Mendel‘s law of independent assortment 孟德儿独立分配定律 Mendel‘s law of segregation 孟德儿分离定律

31. Novel parameters for prenatal selection--- gene testing Carrier screening, which involves indentifying unaffected individuals who carry one copy of a gene for a disease that requires two copies for the diasese to be expressed Preimplantation genetic diagnosis (screening Embryos for disease) Newbone screening Presymptomatic testing for predicting developing adult-onset disorders such as Huntington‘s disease Presymptomatic testing for estimating the risk of developing adult-onset cancers and Alzheimer‘s disease Confirmational diagnosis of a symptomatic individual Forensic/identity testing

32. Gene testing---HD Huntington‘s disease (HD): Usually midlife onset; progressive, lethal, degenerative neurological disease Caused by a single abnormal gene An autosomal dominant disorder

33. Gene testing---SMA One of the neuromuscular diseases. Muscles weaken and waste away (atrophy) due to degeneration of motor neurones which are nerve cells in the spinal cord Gene was located Proximal portion of the long arm of chromosome 5 , 1990

34. Gene testing--- Fanconi Syndrome A disorder in which the proximal renal tubules of the kidney do not properly reabsorb electrolytes and nutrients back into the body Excessive drinking, urination and glucose in the urine Muscle wasting, acidosis and poor condition will also occur

35. Pre-implantation diagnosis Single cell analysis

36. Technology: RT-PCR

37. Technology --- RT-PCR Electrophoresis

38. DNA microarray

39. Gene therapy A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common An abnormal gene could be swapped for a normal gene through homologous recombination The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function The regulation of a particular gene could be altered

40. Dr. Mark Hughes A Professor and Director of Molecular Medicine and Genetics at Wayne State University and Director of the Genomics Center Hub for the State of Michigan's Life Sciences Corridor. His work has centered on understanding gene expression in the early human embryo He pioneered the field of PGD for couples at very high reproductive genetic risk and offers this technology in conjunction with IVF Centers in the U.S. and Canada.

41. Ethical challenges Bypassing the natrual method of conception Creating life in the laboratory Fertilizing more embryos than will be needed Discarding excess embryos Unnatural environment for embryos Contributes to overpopulation

42. Ethical challenges Potential to creat embryos for medical purposes Potential to select embryos Potential to modify embryos

43. Potential to modify embryos Alteration of genetic traits: Beauty/handsome, longevity, healthy

44. Potential to select embryos A girl or boy, you pick?

45. Ethical challenges We can test for lots of things, the question is, should we? --- Dr. Mark Hughes