1. Today: Microbial Genetics Wrap-up Mendelian Genetics Adding Chromosomes to the Mix?? Tomorrow: UW Fieldtrip!

2. Back to Eukaryotes: Bringing in Mendel… If DNA replication and cell division are both so precise, and so accurate, why are we all so unique??

3. Meiosis Creates Genetic Diversity: 1. Independent Assortment Homologous Chromosomes are INDEPENDENTLY (randomly) parceled out during Meiosis I

4. INDEPENDENT ASSORTMENT contributes to GENETIC DIVERSITY

5. 2. CROSS-OVER produces RECOMBINANT CHROMOSOMES, contributing to GENETIC DIVERSITY Cross-over occurs as duplicated chromosomes pair with their homologues in SYNAPSIS. During this process, nonsister chromosomes cross at CHIASMATA.

6. #3: Random Fertilization 8 million possible chromosome combinations in each egg, and each sperm… = >70 trillion possibilities! How are we able to predict ANYTHING about inheritance??

7. Gregor Mendel, 1822-1884 Charles Darwin, 1809-1882 Looking forward to Genetics: The Paradox

8. Setting the Stage for Mendel Leading theory at the time is Blended Inheritance Mendel will need a good model organism! What makes a good model??

9. Mendel’s Technique: Studies peas: Typically Self- Fertilizing Multiple distinct CHARACTERS, with easy to identify TRAITS Several TRUE- BREEDING varieties available

10. What Mendel Observes, Part 1: What does this data suggest about “blended inheritance”?

11. What Mendel Observes, Part 2:

12. How would you explain Mendel’s results? (Can you reconcile what he observed with what we know about chromosomes and meiosis??) Create a hypothesis to explain his new results!

13. Mendel’s Hypothesis- Part 1 Different genes account for the variation in inherited characters

14. For each character, an organism inherits two alleles, one from each parent. Mendel’s Hypothesis- Part 2

15. If the alleles are different, than one will control the organism’s appearance (the dominant allele) while the other will have no noticeable effect (the recessive allele) Mendel’s Hypothesis- Part 3

16. The two alleles are separated during gamete production (At what stage??) Mendel’s Hypothesis- Part 4

17. Testing the Law of Segregation: The Punnett Square

18. The Punnett Square for Mendel’s Experiments: What will the F1 Generation look like? The F2 Generation?

19. The Punnett Square for Mendel’s Experiments:

20. vs

21. Understanding the predicted results of a PUNNETT SQUARE, allows for a TESTCROSS What’s my phenotype? My genotype?

22. Try a Test Cross! Part 1: In dogs, there is an hereditary deafness caused by a recessive gene, “d.” A kennel owner has a male dog that she wants to use for breeding purposes if possible. The dog can hear, so the owner knows his genotype is either DD or Dd. If the dog’s genotype is Dd, the owner does not wish to use him for breeding so that the deafness gene will not be passed on. This can be tested by breeding the dog to a deaf female (dd). Draw the Punnett squares to illustrate these two possible crosses. In each case, what percentage/how many of the offspring would be expected to be hearing? deaf? How could you tell the genotype of this male dog?

23. Using Simple Mendelian Genetics Sickle Cell Disease

24. Sickle Cell Disease Questions: Part 2A: Two individuals who are heterozygous at the Sickle Cell locus have four children together. One of the children is affected with the disorder. Based on this information, is the sickle cell trait dominant or recessive?

25. Sickle Cell Disease Questions: 2B. If the affected offspring has a child with an unaffected individual (who does not carry the sickle allele), what is the probability that any given child will be unaffected? Be a carrier? Be affected?

26. An Aside: Unusual Gene Frequencies!? What do you notice? What does this suggest?

27. Mendelian Genetics- Example 3: Cystic Fibrosis is also an Autosomal Recessive Trait with Unusual Gene Frequencies A. If two carriers of the cystic fibrosis trait have children, what is the probability that their first child will be affected? B. If they eventually have three children, what is the probability that all three will be affected?

28. Calculating Probabilities

29. Huntington’s Disease Figure 1. Samples of coronal and sagittal magnetic resonance imaging from a patient with Huntington's disease (top row) and a normal control (bottom row) showing the outlines of caudate and putamen (left), cerebral (center) and cerebellar volumes (right). H.H. Ruocco, I. Lopes-Cendes, L.M. Li, M. Santos-Silva and F. Cendes. 1129 Striatal and extrastriatal atrophy in Huntington’s disease and its relationship with length of the CAG repeat. Braz J Med Biol Res 2006; 39: 1129-1136

30. Dependent Assortment? Mendel’s Next Question: What happens in a dihybrid cross? What would the outcome look like if it’s dependent assortment??

31. What Mendel Sees: So is it dependent assortment??

32. Try a Messy Dihybrid Cross! 5A. What fraction (or number) of the offspring of the couple described would be homozygous tongue-rollers who are non-tasters (RRtt)??

33. Mendel’s Contributions Law #1: Segregation Law #2: Independent Assortment

34. Complication #1: (Mendel was lucky!) INCOMPLETE DOMINANCE Heterozygotes have a unique phenotype, between that of the homozygous dominant or recessive parents. Note: This is not blended inheritance! Why?

35. Complication #1: (Mendel was lucky!) INCOMPLETE DOMINANCE

36. Another Exception: Codominance In codominance, both alleles affect the phenotype in separate, distinguishable ways. Example: Human blood groups M, N, and MN Group MN produce both antigens on the surface of blood cells

37. Another Exception: Codominance Example: Tay-Sachs disease- Heterozygous individuals produce both functional, and dysfunctional enzymes. A section of the brain of a Tay Sachs child. The empty vacuoles are lysosomes that had been filled with glycolipid until extracted with alcohol in preparing the tissue. organismal level = recessive biological level = codominant

38. Three Important Points about Dominant/Recessive Traits: 1.They range from complete dominance  incomplete dominance  codominance. (can be a subtle distinction!) 2.They reflect mechanisms through which specific alleles are expressed in the phenotype (i.e. this is not one allele subduing another at the DNA level) 3.They’re not related to the abundance of an allele within a population!

39. Further Complications: Multiple Alleles

40. Further Complications: Multiple Alleles

41. Scenario : Suppose mother is Type A, baby is Type B. Consider these three putative fathers: can any be the biological father? #1 (Type A) : Yes or No? #2 (Type B) : Yes or No? #3 (Type O) : Yes or No?Yes or No Practice Question 6: Paternity Testing

42. Further Complications: Pleiotropy Most genes have multiple phenotypic effects!

43. Further Complications: Pleiotropy No production of melanocytes during development causes: 1. White fur color and 2. Inability to transmit electrical signals to brain from hair cells in the ear.

44. More Complications: EPISTASIS Example: The “color gene”, C, allows pigment to be deposited in hair. When lacking, a mouse is albino, regardless of its genotype at the other locus.

45. Epistasis and Lab Pups Black is dominant to Brown, so Heterozygotes (Bb) are black. The delivery gene is also dominant, so EE or Ee individuals both express their pigments. Only ee individuals are yellow. Coat color in labradors is determined by 2 genes, a pigment gene (B), and a pigment delivery gene (E).

46. Your Question (7): If I cross a Brown Lab (bbEe) with a Black Lab (BbEe), can I expect any yellow puppies? If so, what proportion of the pups would I expect to be yellow? Epistasis and Lab Pups

47. There’s more… Polygenic Inheritance This results in a broad norm of reaction

48. Many factors, both genetic and environmental, influence the phenotype. Other Issues: Environmental Effects on Phenotype

49. Similarities between the behavior of chromosomes and Mendel’s “factors”:

50. Chromosomes and genes are both present in paired in diploid cells Homologous chromosomes separate and alleles segregate during meiosis Fertilization restores the paired conditions for both chromosomes and genes Similarities between the behavior of chromosomes and Mendel’s “factors”:

51. In 1902 the Chromosome Theory of Inheritance was proposed. In states that Mendelian genes have specific loci on chromosomes, and these chromosomes undergo segregation and independent assortment. Similarities between the behavior of chromosomes and Mendel’s “factors”:

52. Correlating the results of Mendel’s dihybrid crosses with the behavior of chromosomes during meiosis

53. Thomas Hunt Morgan’s contributions: Fruit Fly Genetics Single mating produces 100+ offspring A new generation can be bred every two weeks Only four pairs of chromosomes- 3 pairs of autosomes, 1 pair sex chromosomes (XX and XY)

54. Unlike Mendel, Morgan does not have access to true- breeding strains. He breeds flies for a year, looking for distinct varieties. He discovers a male fly with white eyes, instead of red. In Drosophila, red eyes = Wild type (the most common phenotype in a natural population) white eyes = a Mutant Phenotype.

55. Morgan’s Results: First Experiment: Morgan crosses a red- eyed female with a white-eyed male. ALL the offspring have red eyes. How would Mendel explain these results?? What would Mendel do next??

56. Next Experiment: Morgan crosses two of the red-eyed F1 flies with each other. What should he see if Mendel is correct?? Morgan’s Results:

57. He DOES find a 3:1 ratio, but ALL the white- eyed flies are male!! Was Mendel wrong?? What happened?!? Morgan’s Results: