1. Biology Sylvia S. Mader Michael Windelspecht Chapter 11 Mendelian Patterns of Inheritance Lecture Outline Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. See separate FlexArt PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes. 1

2. 2 Outline 11.1 Gregor Mendel 11.2 Mendel’s Laws 11.3 Extending the Range of Mendelian Genetics

3. 11.1 Gregor Mendel Austrian monk  Studied science and mathematics at the University of Vienna  Conducted breeding experiments w/ garden pea (Pisum sativum)  Apply mathematics to biology! Formulated laws of heredity: early 1860s  No knowledge of cells or chromosomes  No microscope 3

4. Gregor Mendel Concept of Blending Inheritance:  Parents = contrasting appearance produce offspring = intermediate appearance Mendel’s findings contrasted this  Particulate Theory of Inheritance Inheritance involves reshuffling of “particles” (genes) from generation to generation 4

5. Gregor Mendel 5 land of the lost

6. 6 Gregor Mendel: The garden pea  Organism in Mendel’s experiments  A good choice: Easy to cultivate Short generation self-pollinating, but can be cross-pollinated by hand True-breeding varieties Simple, objective traits

7. Garden Pea Anatomy 7 stamen anther a. Flower Structure filament stigma style ovules in ovary carpel Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

8. 8 All peas are yellow when one parent produces yellow seeds and the other parent produces green seeds. Brushing on pollen from another plant Cutting away anthers Garden Pea Anatomy Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

9. Garden Pea Anatomy Trait *Dominant Characteristics *Recessive Stem length Pod shape Seed shape Seed color Flower position Flower color Pod color b. Green Purple Axial Yellow Round Inflated TallShort Constricted Wrinkled Green Terminal White Yellow Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

10. 11.2 Mendel’s Laws Monohybrid cross:  Used “true-breeding” (homozygous) plants  Varieties differed in 1 trait  Performed reciprocal crosses Parental generation = P First filial generation (offspring) = F 1 Second filial generation (offspring) = F 2  Law of Segregation!!! 10

11. Mendel’s Laws Law of Segregation: 1.Each individual= 2 factors (alleles) for each trait 2.Factors segregate (separate) during gamete (sperm & egg) formation 3.Gamete= 1 factor from each pair 4.Fertilization= offspring has 2 factors for each trait (1 from each parent) 11

12. Mendel’s Laws Classical Genetics & Mendel:  Each trait is controlled by 2 alleles (alternate forms of a gene)  Dominant allele (capital letter) masks the expression of the recessive allele (lower-case)  Alleles occur on homologous pairs at particular gene loci Homozygous = identical alleles Heterozygous = different alleles 12

13. Classical View of Homologous Chromosomes 13 Replication alleles at a gene locus sister chromatids b. Sister chromatids of duplicated chromosomes have same alleles for each gene. a. Homologous chromosomes have alleles for same genes at specific loci. G R S t G R S t G R S t g r s T g r s T g r s T Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

14. Monohybrid Cross done by Mendel 14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. TTtt Phenotypic Ratio short1 tall3 Allele Key T tall plant = t short plant =

15. Monohybrid Cross done by Mendel 15 P generation TTtt Phenotypic Ratio short1 tall3 Allele Key T tall plant = t short plant = Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

16. Monohybrid Cross done by Mendel 16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P generation TTtt t T P gametes Phenotypic Ratio short 1 tall 3 Allele Key T tall plant = t short plant =

17. Monohybrid Cross done by Mendel 17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. tt P generation TTtt t T Tt P gametes F 1 generation Phenotypic Ratio short1 tall3 Allele Key T tall plant = t short plant =

18. Monohybrid Cross done by Mendel 18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. eggs sperm P generation Tt T t TTtt t T Tt P gametes F1 gametes F1 generation Phenotypic Ratio short 1 tall 3 Allele Key T tall plant = t short plant =

19. Monohybrid Cross done by Mendel Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. eggs sperm P generation Tt T t TT tt t T Tt TT P gametes F 1 gametes F 1 generation Phenotypic Ratio short 1 tall 3 Allele Key T tall plant = t short plant = 19

20. Monohybrid Cross done by Mendel 20 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. eggs sperm Tt T t TTtt t T Tt TTTt F 1 gametes Phenotypic Ratio short1 tall 3 Allele key F 1 generation P gametes F 1 generation T tall plant = t short plant =

21. Monohybrid Cross done by Mendel 21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. eggs sperm P generation Tt T t TTtt t T Tt TTTt P gametes F 1 gametes F 1 generation Phenotypic Ratio short 1 tall 3 Allele Key T tall plant = t short plant =

22. Monohybrid Cross done by Mendel 22 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. eggs sperm Offspring P generation Tt T t TTtt t T Tt TTTt tt P gametes F 1 gametes F 2 generation F 1 generation Phenotypic Ratio short1 tall3 Allele Key T tall plant = t short plant =

23. Phenotypic Ratio = 3:1!!! Trait Stem length Pod shape Seed shape Seed color Flower position Flower color Pod color Dominant Characteristics Recessive Tall Inflated Round Yellow Axial Purple Green Short Constricted Wrinkled Green Terminal White Yellow Dominant F 2 Results RatioRecessive Totals: 2.84:1277787 8822992.95:1 2.96:1 3.01:1 3.14:1 3.15:1 2.82:1 2.98:1 2,001 1,8505,474 6,022 651 705 428 14,949 207 224 152 5,010 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

24. G vs. P Genotype  Refers to alleles an individual has  genotype is homozygous (TT, tt)  genotype is heterozygous (Tt) Phenotype  Refers to physical appearance resulting from genotype 24

25. Mendel’s Laws Dihybrid cross- cross 2 true-breeding plants differing in 2 traits  Start w/ true-breeding plants differing in two traits  F 1 plants- dominant for both traits  F 1 self-pollinates 25

26. Mendel’s Laws Law of Independent Assortment 1. Alleles (pair) segregate independently of other alleles (pair) 2.All possible combinations of alleles can occur in gametes Applies only to alleles on different chromosomes!!!  Expected phenotypic ratio of F 2 plants= 9:3:3:1 !!!!! 9=dominant for both traits, 3= dominant for 1 trait, recessive for the other, 1= recessive for both traits 26

27. Dihybrid Cross Done by Mendel Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. × = = = = T t G g 9 3 3 1 ttggTTGG P generation P gametes F 1 generation F 1 gametes F 2 generation sperm eggs TtGg TG tg tGTgTG TtGg Tg tG tg TTGGTTGgTtGG TtggTtGgTTggTTGg ttGgttGGTtGgTtGG ttggttGgTtggTtGg Allele Key Offspring Phenotypic Ratio Yellow pod green pod short plant tall plant tall plant, green pod tall plant, yellow pod short plant, green pod short plant, yellow pod

28. Independent Assortment and Segregation during Meiosis 28 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A a B b Parent cell has two pairs of homologous chromosomes.

29. Independent Assortment and Segregation during Meiosis 29 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A AA a aa B BB b bb either Parent cell has two pairs of homologous chromosomes.

30. Independent Assortment and Segregation during Meiosis 30 A AA a aa B BB b bb AA bbBB aa either or Parent cell has two pairs of homologous chromosomes. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

31. Independent Assortment and Segregation during Meiosis 31 A AA a aa B BB b bb A A bbBB aa either or Parent cell has two pairs of homologous chromosomes. All orientations of ho- mologous chromosomes are possible at meta- phase I in keeping with the law of independent assortment. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

32. Independent Assortment and Segregation during Meiosis 32 A AA AA a a a a a B BB BB b bb AA bbBB aa bb either or Parent cell has two pairs of homologous chromosomes. All orientations of ho- mologous chromosomes are possible at metaphase I in keeping with the law of independent assortment. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

33. Independent Assortment and Segregation during Meiosis 33 A AA AA a a a a a AA aa B BB BB BB b bb AA bbBB aa bb bb either or Parent cell has two pairs of homologous chromosomes. All orientations of ho- mologous chromosomes are possible at metaphase I in keeping with the law of independent assortment. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

34. Independent Assortment and Segregation during Meiosis 34 A AA AA a a a a a AA aa B BB BB BB b bb AA bbBB aa bb bb either or Parent cell has two pairs of homologous chromosomes. All orientations of ho- mologous chromosomes are possible at meta- phase I in keeping with the law of independent assortment. At metaphase II, each daughter cell has only one member of each homologous pair in keeping with the law of segregation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

35. Independent Assortment and Segregation during Meiosis 35 Parent cell has two pairs of homologous chromosomes. All possible combi - tions of chromosomes and alleles occur in the gametes as suggested by Mendel's two laws. All orientations of ho- mologous chromosomes are possible at metaphase I in keeping with the law of Independent assortment. At metaphase II, each daughter cell has only one member of each homologous pair in keeping with the law of segregation A AA AA A A AB ab Ab aB a a a a a a a A A b A aa a B B BB B B B B B B a B b bb AA bbBB aa b b b b b A b b either or Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

36. Mendel’s Laws Punnett Square: Table listing all possible genotypes from a cross All possible sperm genotypes are on one side All possible egg genotypes are on the other side Every possible zygote genotypes are within squares easily calculate probability of genotypes & phenotypes of offspring 36

37. Mendel’s Laws  Punnett square in next slide shows a 50% (or ½) chance The chance of E = ½ The chance of e = ½  An offspring will inherit: The chance of EE =½  ½=¼ The chance of Ee =½  ½=¼ The chance of eE =½  ½=¼ The chance of ee =½  ½=¼ 37

38. Punnett Square 38 eggs spem Punnett square Offspring Parents Ee E e Ee EE Ee Allele key Phenotypic Ratio unattached earlobes 3 1 E = e = unattached earlobes attached earlobes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ee

39. Mendel’s Laws Test crosses  homozygous recessive genotype  recessive phenotype  homozygous dominant OR Heterozygous  dominant phenotype 39

40. One-Trait Testcross 40

41. One-Trait Testcross 41 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. b. tT Tt Offspring eggs sperm TTtt Allele Key Phenotypic Ratio All tall plants T = tall plant t = short plant

42. 42 Mendel’s Laws Two-trait testcross:  dominant pheno. X recessive pheno.  If heterozygous dominant for both traits?  phenotypic ratio is 1:1:1:1  If homozygous dominant for both traits?  all offspring are dominant phenotype

43. Mendel’s Laws Genetic disorders are medical conditions caused by alleles inherited from parents Autosome – chromosomes 1-22 (not X or Y) autosomal disorders: genetic disorders caused by genes on autosomes  Autosomal dominant AA = disorder  Aa = disorder  aa = NO disorder  Autosomal recessive AA = NO disorder Aa = NO disorder, but carrier  aa = disorder  43

44. Autosomal Recessive Pedigree 44 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. I II III IV Key Generations Autosomal recessive disorders Most affected children have unaffected parents. Heterozygotes (Aa) have an unaffected phenotype. Two affected parents will always have affected children. Close relatives who reproduce are more likely to have affected children. Both males and females are affected with equal frequency. A? aa A? Aa A? Aa * A? aa aa = affected Aa = carrier (unaffected) AA = unaffected A? = unaffected (one allele unknown)

45. Autosomal Dominant Pedigree 45 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Affected children usually have affected parent. Heterozygotes (Aa) are affected. Two affected parents can produce an unaffected child. Two unaffected parents will not have affected children. Both males and females are affected with equal frequency. AA = affected Aa = affected A? = affected (one allele unknown) aa = unaffected I II III Aa aa Aa * A? aa Aa Key Generations Autosomal dominant disorders

46. Mendel’s Laws Autosomal Recessive Disorders: 1.Methemoglobinemia Relatively harmless disorder Accumulation of methemoglobin in the blood causes skin to appear bluish-purple 2.Cystic Fibrosis Mucus in bronchial tubes and pancreatic ducts is particularly thick and viscous 46

47. Methemoglobinemia 47 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Courtesy Division of Medical Toxicology, University of Virginia

48. Cystic Fibrosis 48 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cl - H2OH2O H2OH2O H2OH2O thick mucus defective channel nebulizer percussion vest © Pat Pendarvis

49. Mendel’s Laws Autosomal Dominant Disorders: 1.Osteogenesis Imperfecta Weakened, brittle bones Most cases are caused by mutation in genes required for synthesis of type I collagen 2.Hereditary Spherocytosis Caused by a mutation in ankyrin-1 gene Red blood cells become spherical, are fragile, and burst easily 49

50. 11.3 Extending the Range of Mendelian Genetics Some traits are controlled by multiple alleles (multiple allelic traits) >2 allelic forms, but each individual= 2 alleles 1. Codominance: >1 allele fully expressed  Ex. ABO blood type  Both I A and I B are expressed in presence of the other  Alleles: I A = A antigen on red blood cells, anti-B antibody in plasma I B = B antigen on red blood cells, anti-A antibody in plasma i = Neither A nor B antigens on red blood cells, both anti-A and anti- B antibodies in plasma 50

51. ABO Blood Type 51 Genotype I A I A, I A i I B I B, I B i I A I B ii Phenotype A B AB O

52. Extending the Range of Mendelian Genetics 2. Incomplete Dominance: Heterozygote has intermediate phenotype between either homozygote Homozygous red has red phenotype Homozygous white has white phenotype Heterozygote has pink (intermediate) phenotype  Phenotype reveals genotype w/out test cross!! 52

53. Incomplete Dominance 53 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. R 1 R 2 R 1 R 2 R 1 R 2 R 1 R 2 R 1 R 1 R 2 R 2 R 1 R 2 R 1 R 2 eggs sperm Offspring Key 1 R 1 R 1 2 R 1 R 2 1 R 2 R 2 red pink white

54. 54 Human ex:  Familial Hypercholesterolemia (FH) Homozygotes (F 1 F 1 ) for mutant allele develop fatty deposits in skin & tendons, may have heart attacks during childhood Heterozygotes (F 1 F 2 ) may suffer heart attacks during early adulthood Homozygotes (F 2 F 2 ) for normal allele- No disorder Incomplete Dominance

55. 55 Human ex: 2A. Incomplete penetrance dominant allele may not always lead to dominant phenotype in heterozygote Many dominant alleles exhibit varying degrees of penetrance Ex: polydactyly –Extra digits on hands, feet, or both –Not all individuals who inherit dominant polydactyly allele will exhibit the trait (have an extra digit) Incomplete Dominance

56. Extending the Range of Mendelian Genetics 3. Pleiotropy: 1 mutant gene affects >2 distinct, seemingly unrelated traits.  Ex. Marfan syndrome: Mutations in connective tissue result in: disproportionately long arms, legs, hands, and feet weakened aorta poor eyesight 56

57. Marfan Syndrome 57 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chest wall deformities Long, thin fingers, arms, legs Scoliosis (curvature of the spine) Flat feet Long, narrow face Loose joints SkeletonSkinLungsEyes Lens dislocation Severe nearsightedness Collapsed lungs Stretch marks in skin Recurrent hernias Dural ectasia: stretching of the membrane that holds spinal fluid Mitral valve prolapse Enlargement of aorta Heart and blood vessels Aneurysm Aortic wall tear Connective tissue defects (Left): © AP/Wide World Photos; (Right): © Ed Reschke; (Sickled cells, p. 203): © Phototake, Inc./Alamy

58. Extending the Range of Mendelian Genetics 4. Polygenic Inheritance:  1 trait governed by >2 genes w/ different alleles  dominant alleles have quantitative & additive effect on phenotype  Results in continuous variation of phenotypes w/in pop.  traits may be affected by environment  Examples Human skin color Height Eye color 58

59. Polygenic Inheritance 59 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. aabbcc Aabbcc AaBbcc AaBbCc AABbCc AABBCc AABBCC 20 — 64 15 — 64 6 — 1 Proportion of Population Genotype Examples F 2 generation — F 1 generation P generation

60. Extending the Range of Mendelian Genetics 5. X-Linked Inheritance  X-linked genes carried on X chromosome.  Y chromosome doesn’t carry these genes  Males are affected more than females!  Discovered in early 1900s by group at Columbia University; Thomas Hunt Morgan. Performed experiments w/ fruit flies –easily & inexpensively raised –have same sex chromosome pattern as humans 60

61. X – Linked Inheritance 61 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. XrYXrY XRYXRY XRXR XrXr Y XrYXrY XrXr XRXR Y Offspring eggs sperm P generation P gametes F 2 generation F 1 generation F 1 gametes Allele Key = = XRXR XrXr red eyes white eyes Phenotypic Ratio all red-eyed red-eyed white-eyed females: males: 1 1 XRYXRY XRXrXRXr XRXRXRXR XRXR XRXrXRXr XRXRXRXR

62. X-linked Recessive Disorders Color blindness  allele for blue-sensitive protein is autosomal  alleles for the red- and green-sensitive pigments are on X chromosome. Menkes syndrome  defective allele on X chromosome  Disrupts movement of copper in/out of cells.  Phenotypes include kinky hair, poor muscle tone, seizures, and low body temperature  Rare, but fatal by 1-2 yrs Muscular dystrophy  Wasting away of muscle  Caused by absence of muscle protein dystrophin  Fatal by 20 yrs 62

63. X-linked Recessive Disorders Adrenoleukodystrophy  Failure of carrier protein to move enzyme or v. long chain fatty acid into peroxisomes.  Fatty acids build up in cell, cause severe damage to nervous system  Fatal by 5-6 yrs Hemophilia  Absence or minimal presence of clotting factor VIII or clotting factor IX  Blood does not clot or clots very slowly  Queen Victoria was a carrier!! Spread disease to other royal families 63

64. X-Linked Recessive Pedigree 64 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. XBXBXBXB XbYXbY grandfather daughterXBXbXBXb XBYXBYXBYXBYXbXbXbXb XbYXbY XBXbXBXb grandson XBYXBYXBXBXBXB XbYXbY Key X B X B = Unaffected female X B X b = Carrier female X b X b = Color-blind female X b Y = Unaffected male X b Y = Color-blind male X-Linked Recessive Disorders More males than females are affected. An affected son can have parents who have the normal phenotype. For a female to have the characteristic, her father must also have it. Her mother must have it or be a carrier. The characteristic often skips a generation from the grandfather to the grandson. If a woman has the characteristic, all of her sons will have it.