Today: Onward through Mendelian Genetics and Exceptions Adding Chromosomes to the Story

1. Today: • Onward through Mendelian Genetics and Exceptions • Adding Chromosomes to the Story

2. Testing Mendel’s Law of Segregation: The Punnett Square

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

4. The Punnett Square for Mendel’s Experiments:

5. vs

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

7. Using Simple Mendelian Genetics Sickle Cell Disease

8. Sickle Cell Disease Questions: • 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?

9. Sickle Cell Disease Questions: 2. 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?

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

11. Mendelian Genetics- Example 2: Cystic Fibrosis is also an Autosomal Recessive Trait with Unusual Gene Frequencies • If two carriers of the cystic fibrosis trait have children, what is the probability that their first child will be affected? • It they eventually have three children, what is the probability that all three will be affected?

12. Calculating Probabilities

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

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

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

16. Practice Problem: Monohybrid Cross In pea plants, spherical seeds (S) are dominant to dented seeds (s). In a genetic cross of two plants that are heterozygous for the seed shape trait, what fraction of the offspring should have spherical seeds? • None B. ¼ • C. ½ D. ¾ • E. All

17. Practice Problem: Dihybrid Cross In a dihybrid cross, AaBb x AaBb, what fraction of the offspring will be homozygous for both recessive traits? • 1/16 B. 1/8 • C. 3/16 D. 1/4 • E. 3/4

18. 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?

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

20. 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

21. Another Exception:Codominance Example: Tay-Sachs disease- Heterozygous individuals produce both functional, and dysfunctional enzymes. organismal level = recessive, biological level = codominant. 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.

22. Three Important Points about Dominant/Recessive Traits: • They range from complete dominance  incomplete dominance  codominance. (can be a subtle distinction!) • 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) • They’re not related to the abundance of an allele within a population!

23. Codominance Practice Question: • The Palomino horse is a hybrid exhibiting a golden color with lighter mane and tail. • A pair of codominant alleles (D1 and D2) control the inheritance of these coat colors. • Genotypes homozygous for the D1 allele are chestnut-colored (reddish), heterozygous genotypes are Palamino-colored, and genotypes homozygous for the D2 allele are almost white and called cremello.

24. Codominance Practice Question: • 1. From the matings between two Palaminos, determine the expected Palamino : non-Palamino ratio among the offspring. • What percentage of the non-Palamino offspring in part 1 will breed true? • 3. What kind of mating will produce only Palaminos?

25. From the matings between two Palaminos, determine the expected Palamino : non-Palamino ratio among the offspring. • P = D1D2 x D1D2F1 = 1/4 D1D1 + 1/2 D1D2 + 1/4 D2D2Ratio 1 Palomino : 1 non-Palomino • What percentage of the non-Palamino • offspring in part (a) will breed true? • all non-Palomino offspring will breed true • (c) What kind of mating will produce only Palaminos? • chestnut-colored x cremello will produce all Palominos

26. Further Complications: Multiple Alleles

27. Further Complications: Multiple Alleles

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

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

30. 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.

31. 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.

32. Epistasis and Lab Pups Coat color in labradors is determined by 2 genes, a pigment gene (B), and a pigment delivery gene (E). 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.

33. Epistasis and Lab Pups Your Question: 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?

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

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

36. Next: Creating the CHROMOSOME THEORY OF INHERITANCE

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

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

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

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

41. 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)

42. 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.

43. 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??

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

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

46. Morgan Discovers Sex-Linked Genes! (and wins Nobel Prize, 1933)

47. Sex Determination Happens in a Variety of Ways Sex chromosomes (especially the X chromosome) carry genes for many other characters. In humans, the term “sex-linked” generally refers to genes on the X chromosome.

48. The Transmission of SEX-LINKED RECESSIVE Traits In this diagram “A” represents a dominant allele carried on the X chromosome; “a” represents the recessive allele. White boxes indicate unaffected individuals, light-colored boxes are carriers, and dark-colored boxes are affected individuals. Note that both males and females are affected by sex-linked disorders!

49. An Aside: X Inactivation in Female Mammals

50. In females, one X chromosome is inactivated (at random) and condenses into a compact Barr body along the inside of the nuclear envelope. Most genes on this X chromosome are not expressed. Because it is random which X chromosome forms the Barr body during development, females are Mosaics of the two cell types.