1. Wheeler High School The Center for Advanced Studies in Science, Math & Technology Course Introduction Genetics Lecture 1 Post-AP DNA/Genetics – Mrs. Kelavkar

2. What Is A Gene? We shall begin with the physical definition of a gene. Conceptually, this is quite simple and gives us a chance to refresh our minds. Post-AP DNA/Genetics – Mrs. Kelavkar

3. Genes are made of DNA

4. Watson & Crick 1953 Deduced structure of DNA as double helix –With a little help from Rosalind Franklin Complementary base pairing (Chargaff) –Showed how information could be encoded in a molecule & duplicated Thus REPLICATION Post-AP DNA/Genetics – Mrs. Kelavkar

5. Gene Expression: From DNA to Phenotype TRANSCRIPTION –Uses complementary base pairing –Makes mRNA RNA is chemically less stable than DNA Think of mRNA as a temporary molecule that stores DNA’s information Post-AP DNA/Genetics – Mrs. Kelavkar

7. TATA binding protein Initiation of Transcription DNAGG TATA Transcription begins Promoter Gene sequence to be transcribed TATA box Transcription begins at the 5’ end of the gene in a region called the promoter. When a complete transcription complex is formed RNA polymerase binds and transcription begins. The promoter recruits TATA protein, a DNA binding protein, which in turn recruits other proteins. Transcription factor

8. The process of reading the RNA sequence of an mRNA and creating the amino acid sequence of a protein is called translation. Transcription Codon Translation DNA TT CAG T CAG template strand mRNA AAGUCAGUC Messenger RNA Protein LysineSerineValine Polypeptide (amino acid sequence) Translation

9. Make me a protein! (Remember…”Structure equals function”) You see… it’s all about the proteins.

10. Cellular processes depends on protein structure AND the amino acid combinations that make them!

11. Having Said That… What is a GENE? A DNA segment that is needed to make a protein. Post-AP DNA/Genetics – Mrs. Kelavkar

12. Genes Usually 10 3 – 10 4 bp in size –Human dystrophin gene is 2 x 10 6 bp Connects muscle fibers to cell membrane E. coli has ~4,200 genes –Not very many –There are more than 1,000 different enzymes needed to carry out the necessary biological reactions in an E. coli cell Post-AP DNA/Genetics – Mrs. Kelavkar

13. Dystrophin Connects the muscle fibers to the cell’s membrane through the extra- cellular matrix. ‘Irregular’ dystrophin = muscular dystrophy Post-AP DNA/Genetics – Mrs. Kelavkar

14. More Complex Organisms Humans have ~35,000 genes –Genes are located on chromosomes There is a fairly predictable flow to it all… Gene → Protein → Cell Processes → Organism It may be simple, but it illustrates 2 very powerful aspects of genetic analysis. Post-AP DNA/Genetics – Mrs. Kelavkar

15. The 2 Important Aspects 1.We can study microscopic changes in DNA and these changes are revealed by phenotype 2.We can study the function of individual proteins by examining the consequences of eliminating that one protein function (‘knockout’ mice) These are 2 of the main themes studied in genetics!

17. Some Terms You Should Know Alleles: Different versions of the same gene Mutation: An altered version of a gene Genotype: All of the alleles in an organism Phenotype: The physical result of the genotype Wild Type: It’s the standard (think of it like the control) Post-AP DNA/Genetic – Mrs. Kelavkar

18. Any Questions? Post-AP DNA/Genetics – Mrs. Kelavkar

19. Wheeler High School The Center for Advanced Studies in Science, Math & Technology Model Organisms & Key Players Genetics Lecture 2 Post-AP DNA/Genetics – Mrs. Kelavkar

20. Table 1-2 Copyright © 2006 Pearson Prentice Hall, Inc.

21. Model Organisms Why do genetic studies rely on the use of model organisms? 1.Short life cycle 2.Easy to maintain in the lab (usually ) 3.Lots of offspring 4.Fairly straightforward genomes & anatomy Post-AP DNA/Genetics – Mrs. Kelavkar

22. Escherichia coli E. coli Gram negative Different serotypes –Different serotypes = different surface antigens Named after Austrian doctor, Theodor von Escherich, who isolated it from the intestines of animals –Isolated in 1922 –First bacterium to have genome sequenced –~4.6 million bases –Important because it has many genes that are found in common organisms Post-AP DNA/Genetics – Mrs. Kelavkar

23. Escherichia coli E. coli Studied by many early geneticists –Most famous is Avery, MacLeod & McCarty’s 1944 experiment illustrating transformation Remember that “transformation” was first described by Griffith in 1928 –Experiment showed DNA was genetic material Post-AP DNA/Genetics – Mrs. Kelavkar

24. Figure 1-7 Copyright © 2006 Pearson Prentice Hall, Inc. T Phage infecting E. coli Viruses that infect bacteria are called bacteriophages (geeky geneticists call them ‘phages’ for short). Seymour Benzer genetically mapped >2400 mutations in the T4 rII gene.

25. Saccharomyces cerevisiae Yeast Why do geneticists love yeast? 1.Non pathogenic eukaryote 2.Grows rapidly on glucose 3.Easy transformation 4.~6,000 genes, all sequenced

26. Drosophila melanogaster Fruit fly Used to study human- specific diseases 3 pairs of autosomes and an X and Y Life cycle & mating behavior very well understood –Morgan & Benzer –Many mutants identified –Almost ALL genes have human orthologs Figure 1-6 Copyright © 2006 Pearson Prentice Hall, Inc.

27. Drosophila melanogaster Fruit fly Thomas Hunt Morgan & his “Raiders” Discovered the following (and many more): –White-eye mutation –Sex-linkage & segregation –Nondisjunction & crossing-over –The “clock” gene Benzer worked on this too. He was convinced that our circadian rhythms had a genetic basis. –“Notch” gene Led to discovery of Huntington’s mutation Post-AP DNA/Genetics – Mrs. Kelavkar

28. Caenorhabditis elegans C. elegans Soil dwelling nematode ~1 mm Sydney Brenner (1974) Has nervous system First multicellular organism to have it’s genome sequenced Many conserved protein sequences & human orthologs –Shows quick evolutionary patterns Post-AP DNA/Genetics – Mrs. Kelavkar

29. Danio rerio Zebrafish Vertebrate, Freshwater Used to study embryonic development and development of vertebrates –Large, transparent eggs Mutations in the two cell singaling genes, PSEN1 and PSEN2, are studied in zebrafish –Mutations in these genes can lead to Alzheimers disease Post-AP DNA/Genetics – Mrs. Kelavkar Mutation in the pigment gene (1 bp difference in humans).

30. Mus musculus The common mouse Mammals and therefore share a high degree of homology with humans ~3 billion bp’s Knockout mice – gene is ‘knocked out’; used to study function of genes Oncomice – activated oncogene mutant; lead to cancer Transgenic mice – foreign genes inserted in to their genome Post-AP DNA/Genetics – Mrs. Kelavkar

31. What causes obesity? Genetics, environment, combo of both? Post-AP DNA/Genetics – Mrs. Kelavkar

32. Some Terms You Should Know Homologue: A gene related to a second gene by descent from a common ancestral DNA sequence. There are 2 main types of homologues… –Ortholog: genes in different species that evolved from a common ancestral gene by speciation (normally, orthologs retain the same function in the course of evolution) Always the result of speciation –Paralogs: genes related by duplication within a genome Orthologs retain the same function in the course of evolution, whereas paralogs evolve new functions Post-AP DNA/Genetics – Mrs. Kelavkar

33. Any Questions? Yes…we will study C. elegans and you will need to understand their mating patterns. Post-AP DNA/Genetics – Mrs. Kelavkar

34. 1.1From Mendel to DNA in Less Than a Century 1.1.2The Chromosome Theory of Inheritance: Uniting Mendel and Meiosis

35. Figure 1-2 Copyright © 2006 Pearson Prentice Hall, Inc.

36. Figure 1-3 Copyright © 2006 Pearson Prentice Hall, Inc.

37. Figure 1-5 Copyright © 2006 Pearson Prentice Hall, Inc.

38. 1.1From Mendel to DNA in Less Than a Century 1.1.3Genetic Variation Mendel 1857

39. 1.1From Mendel to DNA in Less Than a Century 1.1.4The Search for the Chemical Nature of Genes: DNA or Protein? Fredrick Griffith 1928 Non-virulent bacteria transformed to virulent strain Thomas Morgan 1933 Chromosome as heredity material

40. 1.2Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.1The Structure of DNA and RNA Rosalind Franklin 1953-56 Maurice Wilkins and Watson & Crick 1953-58

41. Figure 1-8 Copyright © 2006 Pearson Prentice Hall, Inc.

42. 1.2Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.2Gene Expression: From DNA to Phenotype Edwin Chargaff 1940’s AT & GC Complimentary rule

43. Figure 1-9 Copyright © 2006 Pearson Prentice Hall, Inc.

44. 1.2Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.3Proteins and Biological Function Messelson and Stahl Semiconservative mode of replication 1958-59

45. Figure 1-10 Copyright © 2006 Pearson Prentice Hall, Inc.

46. 1.2Discovery of the Double Helix Launched the Recombinant DNA Era 1.2.4Linking Genotype to Phenotype: Sickle-Cell Anemia

47. Figure 1-11 Copyright © 2006 Pearson Prentice Hall, Inc.

48. Figure 1-12 Copyright © 2006 Pearson Prentice Hall, Inc.

49. Figure 1-13 Copyright © 2006 Pearson Prentice Hall, Inc.

50. 1.3Genomics Grew Out of Recombinant DNA Technology 1.3.1Making Recombinant DNA Molecules and Cloning DN

51. Figure 1-14 Copyright © 2006 Pearson Prentice Hall, Inc.

52. 1.3Genomics Grew Out of Recombinant DNA Technology 1.3.2Sequencing Genomes: The Human Genome Project 1992-93 Beginning 2002-2003 Completed Craig Venter Celera Genomics & J. Craig Venter Institute Francis Collins Physician - geneticist Director of National Institutes of Health

53. Figure 1-15 Copyright © 2006 Pearson Prentice Hall, Inc.

54. 1.4The Impact of Biotechnology Is Growing 1.4.1Plants, Animals, and the Food Supply

55. Table 1-1 Copyright © 2006 Pearson Prentice Hall, Inc.

56. Figure 1-16 Copyright © 2006 Pearson Prentice Hall, Inc.

57. 1.4The Impact of Biotechnology Is Growing 1.4.2Who Owns Transgenic Organisms?

58. Figure 1-18 Copyright © 2006 Pearson Prentice Hall, Inc.

59. 1.5Genetic Studies Rely On the Use of Model Organisms Why? What are the advantages to researchers?

60. 1.5Genetic Studies Rely On the Use of Model Organisms 1.5.1The Modern Set of Genetic Model Organisms

61. 1.5Genetic Studies Rely On the Use of Model Organisms 1.5.2Model Organisms and Human Diseases Zoonotic Diseases Animals to Humans transmission & visa versa