Mendelian Genetics: How a monk and his peas changed the world

1. Mendelian Genetics: How a monk and his peas changed the world January 18, 2008

2. La Ferrassie, France Neandertal Qafzeh, Israel Modern Human

3. Today’s Talk: • Briefly run through the basics of Mendelian genetic principles • Talk about Mendelian applications to humans

4. Darwin’s Problem: • Generally not known how hereditary information was passed from generation to generation

5. Early Concepts of Inheritance The Humunculus

6. Early Concepts of Inheritance + • Blending Inheritance: • Discredited 19th century idea of heredity • Each parent contributed equally, but they blended together, like two buckets of paint

7. Blending Inheritance

8. Gregor Mendel • Born in 1822 • Czech Republic • Joined priesthood as his only way of furthering his education

9. Mendel’s Experiments Mendel’s seven different pea plant characteristics

10. Yellow Seed crossed w/ Green Seed P1 F1 All Yellow Self-fertilize F1 Plants ¾ Yellow ¼ Green F2 Mendel’s Experiments: Seed Color

11. Dominant: The trait expressed in the F1 generation or the allele that prevents expression of the recessive trait Recessive: The trait unexpressed in the F1 generation but re-expressed in some members of the F2 generation or the unexpressed allele in the heterozygote

12. Homozygote YY gg Y Y Y Y g g g g Heterozygote Yg Yg Yg Yg

13. Definitions Phenotype = or YY, Yg, or gg Genotype = Different genotypes can have the same phenotype

14. b B What was actually happening… Original Cell BB bb Chromosome Pairs Split and Each Duplicated BB bb B B b b

15. Yellow Seed crossed w/ Green Seed P1 F1 All Yellow Self-fertilize F1 Plants ¾ Yellow ¼ Green F2 Mendel’s Experiments: Seed Color gg YY Yg Yg Yg Yg

16. Yg Yg Yg Yg g g Y Y YY gg Punnett Square

17. F1 SwYg Self-fertilize F1 Plants F2 9/16 Smooth Yellow 3/16 Smooth Green 3/16 Wrinkled Yellow 1/16 Wrinkled green Two Traits P1 SSYY wwgg

18. Punnett Square YS Yw gS gw YS YYSS YYSw YgSS YgSw Yw YYSw YYww YgSw Ygww gS YgSS YgSw ggSS ggSw gw YgSw Ygww ggSw ggww

19. What was actually happening…

20. What Mendel really figured out… 1) Heredity traits are governed by discrete units (genes) that do not blend 2) Different forms of genes for the same trait (alleles) express dominant and recessive relationships 3) Genes are sorted out into gametes independently of each other

21. After Mendel • No one read it, not even Darwin • “Re-discovered” in 1900

22. Mendelian Genetics:When it works… Sickle-Cell Anemia

23. Case Study: Sickle-cell Anemia Normal Red Blood Cell Sickle Red Blood Cell • Abnormal hemoglobin causes Sickle-shaped red blood cell

24. Case Study: Sickle-cell Anemia • Effects of Sickle Cell Anemia: • Poor oxygen transport • Easily tired • Blood vessel blockage • Pain • Ulcers and sores • Stroke • Paralysis • Death

25. s s A As As A As As Only heterozygotes produced Case Study: Sickle-cell Anemia s = Sickle Cell (Recessive) A = Normal (Dominant) s A AA As A AA As A 1:1 ratio

26. Case Study: Sickle-cell Anemia s = Sickle Cell (Recessive) A = Normal (Dominant) s s A s As As A A AA As s ss ss s As ss 1:1ratio 1:2:1ratio

27. If the homozygote recessive combination is lethal, why is the sickle cell allele is in the gene pool?

28. Case Study: Sickle-cell Anemia Distribution of Sickle-Cell alleles (Darker colors indicate an increasing percentage of people carrying the allele) Malaria Zones, 1920

29. Case Study: Sickle-cell Anemia Heterozygote advantage: • Those who are homozygous sickle-cell (ss) do tend to die early and painfully • Those who are homozygous for the normal blood allele (AA) have a tendency to catch malaria, which kills you even faster than sickle-cell • But the heterozygotes (As) don’t die of sickle-cell and are resistant to malaria

30. Case Study: Sickle-cell Anemia As AA ss

31. Case Study: Sickle-cell Anemia

32. When is a genotype not a phenotype? • Temperature Regulated

33. Testosterone 1 (in utero) Masculinize gentalia in utero Testosterone 2 (at puberty) Masculinize gentalia at puberty When is a genotype not a phenotype? Testis 5 alpha-reductase deficiency

34. Mendelian Genetics:When it doesn’t work… The American Eugenics Movement

35. American Eugenics

36. American Eugenics • American Social Origins: • Labor unrest • Rising immigration • Declining birthrate among wealthy • Failure of social programs to mitigate urban poverty

37. American Eugenics • Charles Davenport: • Zoologist from Harvard • Director of Cold Springs Harbor lab 1904 • Founder of American Eugenics Movement

38. American Eugenics:Research Methods

39. American Eugenics:Research Methods

40. American Eugenics: The Threat of the Feeble-minded They were feeble-minded, and no amount of education or good environment can change a feeble-minded individual into a normal one, any more than it can change a red-haired stock into a black-haired one. -- Henry Goddard, in The Kallikak Family, a eugenics family history

41. American Eugenics:Better babies, fitter families “Yea, I have a goodly heritage” Fitter Families Winner, Large Family division, 1925

42. American Eugenics: Immigration and Marriage Laws

43. American Eugenics: Sterilization Laws First state to institute a sterilization law was Indiana (1907) Eventually, 33 states would follow their lead

44. American Eugenics: Sterilization Laws • Based on a model law from Cold Spring Harbor researcher: • Advocated sterilization for“feeble-minded, insane, criminalistic, epileptic, inebriate, diseased, blind, deaf, deformed, and dependent, including orphans, ne’er-do-wells, tramps, the homeless, and paupers”

45. American Eugenics: Buck vs. Bell • Famous legal case of Buck vs. Bell in 1927 to test the legality of Virginia’s sterilization law Carrie Buck and her mother, a day before the trial

46. American Eugenics: Buck vs. Bell It is better for all the world, if instead of waiting to execute degenerate offspring for crime or let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind…Three generations of imbeciles is enough. -- Justice Oliver Wendell Holmes, Jr.

47. American Eugenics: Buck vs. Bell They done me wrong. They done us all wrong. -- Carrie Buck, shortly before her death, in 1983 Last picture of Carrie Buck taken before her death

48. American Eugenics: Sterilization Laws • In the end, 66,000 people were legally sterilized in the name of Eugenics, and improving the human race through the new science of heredity • Some states were still sterilizing people in the 1970’s

49. American Eugenics:Sterilization Laws “I have studied with great interest the laws of several American states concerning prevention of reproduction by people whose progeny would, in all probability, be of no value or be injurious to the racial stock…” - Adolf Hitler

50. American Eugenics: The Take-Home Message • Genetics in humans are usually more complicated than simple Mendelian systems • Multiple alleles (Blood types, co-dominant) • Multiple affects of a single gene • Environmental interactions (height)