1. Chapter 15 Chromosomes, Morgan & Mutations

2. Figure 15-01

5. Chromosome Basis of Inheritance Genes have specific positions on chromosomes It is the chromosomes that undergo segregation and independent assortment

7. LE 15-2a P Generation Gametes Meiosis Yellow-round seeds (YYRR) Fertilization Green-wrinkled seeds (yyrr) All F 1 plants produce yellow-round seeds (YyRr)

8. LE 15-2b All F 1 plants produce yellow-round seeds (YyRr) Meiosis Two equally probable arrangements of chromosomes at metaphase I Anaphase I LAW OF INDEPENDENT ASSORTMENT Metaphase II Gametes F 1 Generation LAW OF SEGREGATION

9. LE 15-2c Fertilization among the F 1 plants F 2 Generation

10. Why use Fruit Flies in genetic experiments? Small / vials can hold hundreds Short Generation Time Many offspring Only 8 chromosomes

11. Morgan originally an Embryologist He was the one that came up with the term “Wild Type” for the trait that was normally found in nature All other traits he called “Mutants” Born in Lexington, KY - 1866 Awarded the Nobel Prize 1933 (Physiology & Medicine) Died in 1945

12. Figure 15-03

13. More Morgan Sex linked traits He was responsible for determining that genes are located on the “X” chromosome

14. LE 15-4a P Generation F 1 Generation F 2 Generation

15. LE 15-4b P Generation F 1 Generation Ova (eggs) Sperm F 2 Generation Ova (eggs) Sperm

16. Linked Genes Each chromosome has hundreds or even thousands of genes Genes that are on the same chromosome and are close together are called linked genes Often these are inherited together

17. Linked Genes – Two Traits Morgan did other experiments with fruit flies to see how linkage affects inheritance of two or three traits Morgan crossed flies that differed in traits of body color, wing size and/or eye color.

18. LE 15-UN278-1 Parents in testcross Most offspring or

19. LE 15-5 P Generation (homozygous) Parental-type offspring Double mutant (black body, vestigial wings) Recombinant (nonparental-type) offspring b b vg vg Double mutant (black body, vestigial wings) b b vg vg Ova Sperm TESTCROSS 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Wild type (gray body, normal wings) b + b + vg + vg + F 1 dihybrid (wild type (gray body, normal wings) b + b vg + vg

20. Morgan & Crossing Over He discovered that genes can be linked, but sometimes the connection between genes on the same chromosome appears to break Morgan realized that crossing over of homologous chromosomes – was responsible for this

21. LE 15-6a Testcross parents Gray body, normal wings (F 1 dihybrid) Sperm Ova Gametes Replication of chromosomes Black body, vestigial wings (double mutant) Replication of chromosomes Meiosis I and II: No new allele combinations are produced. Meiosis I: Crossing over between b and vg loci produces new allele combinations. Recombinant chromosomes Meiosis II: Separation of chromatids produces recombinant gametes with the new allele combinations.

22. LE 15-6b Parental-type offspringRecombinant offspring Ova Sperm 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Testcross offspring Recombination frequency 391 recombinants 2,300 total offspring  100 = 17% = Gametes Ova Sperm

23. Parentals & Recombinants Morgan noticed that sometimes traits in the offspring were different than either parent Offspring with a phenotype matching one of the parental phenotypes are called parental types Offspring with nonparental phenotypes (new combinations of traits) are called recombinants A 50% frequency of recombination is observed for any two genes on different chromosomes

24. LE 15-UN278-2 Gametes from green- wrinkled homozygous recessive parent (yyrr) Parental-type offspring Gametes from yellow-round heterozygous parent (YyRr) Recombinant offspring

25. Linkage Map Alfred Sturtevant: one of Morgan’s protégés, made a genetic map, a list of the location of genes “loci” on a chromosome He predicted that the farther apart two genes are, the higher the chance that a crossover will occur, so the higher the recombination frequency

26. Map units or CentiMorgans = cM A linkage map is a genetic map of a chromosome based on recombination frequencies Distances between genes can be shown as map units: –one map unit, or centimorgan = 1% recombination frequency Map units indicate relative distance and order, not exact locations of genes

27. LE 15-7 Recombination frequencies 9%9.5% 17% bcn vg Chromosome

28. Cytogenetic Maps Unlike linkage maps that just show general position – Cytogenetic maps show the positions of genes and the chromosomal features “banding patterns” exact locations

30. LE 15-8 Short aristae Black body Cinnabar eyes Mutant phenotypes Vestigial wings Brown eyes Wild-type phenotypes Red eyes Normal wings Red eyes Long aristae (appendages on head) Gray body 104.567.0 57.548.5 0 III I IV X Y II

31. Morgan’s gene representation: For example: –b = black = mutant –b+ = normal body = WILD –vg = vestigial = mutant –vg+ = normal wings = WILD –w = white = mutant –w+ = red eyes (normal) = WILD – ♀ = female – ♂ = male

32. Example Wild (normal) body & Wild (normal) wings crossed with a Black body & Vestigial wings: –b+ b+ vg+ vg+ X b b vg vg –AABB x aabb (representing the same thing) RESULT: –b+ b vg+ vg (heterozygote) –This is sometimes confusing – –AaBb = same thing – much easier

33. If on separate chromosomes & not linked Aa Bb X aabb Counts will be even: –100AB (AaBb) –100Ab(Aabb) –100aB(aaBb) –100ab(aabb) AaBbAabbaaBbaabb ABAbaBab ab

34. If genes located on same chromosome = LINKED … Aa Bb X aabb Counts will be NOT even: –150AB (AaBb) –50Ab(Aabb) –50aB(aaBb) –150ab(aabb) To calculate the map distance: – add the recombinants (50 + 50) / total (400) 100/400 = 25 (x 100) = 25% cM

35. Three Point Cross AABBCC x aabbcc = AaBbCc AaBbCc x aabbcc (test cross counts) – to determine the linkage distance: Example: –ABC 95aBC50 –ABc5aBc700 –AbC700abC5 –Abc50abc95

36. A few hints … –ABC 95aBC50 –ABc5aBc700 –AbC700abC5 –Abc50abc95 Parentals: (largest number) AbC & aBc –Notice they are reciprocals AbC & aBc Recombinants: all others Double Crossovers: the smallest number & the “middle” gene (ABc & abC)

37. –ABC 95aBC50 –ABc5aBc700 –AbC700abC5 –Abc50abc95 Compare Parentals & Double Crossovers: –ABc5abC5 –aBc700AbC700 Notice the only gene that is different when comparing the two is the “A” gene That tells you that “A” is in the middle

38. It is an excellent idea to rewrite the offspring chart in correct order … –ABC 95aBC50 –ABc5aBc700 –AbC700abC5 –Abc50abc95 ------------------------------------ –BAC 95BaC50 –BAc5Bac700 –bAC700baC5 –bAc50bac95

39. Calculations –BAC 95BaC50 –BAc5Bac700 –bAC700baC5 –bAc50bac95Total: 1700 95 + 95 + 5 + 5 = 200/1700 = 11.8 (bet. B & A) 50 + 50 + 5 + 5 = 110/1700 = 6.5 (bet. A & C) 95 + 95 + 50 + 50 = 290/1700 = 17.1 (bet. B & C) –(all of the above totals are x 100) = 11.8 / 6.5 / 17.1

40. Order of genes B A C 11.8 6.5 17.1

42. Sex Determination An organism’s sex is determined by the presence or absence of certain chromosomes In humans and other mammals, there are two sex chromosomes, X and Y Other animals have different chromosome arrangement to determine male / female

43. LE 15-UN282 X Y

44. LE 15-9a The X-Y system Parents Sperm Ova Zygotes (offspring)

45. LE 15-9b The X-0 system Grasshoppers, Cockroaches, Crickets, Praying Mantis & some other insects

46. LE 15-9c The Z-W system Birds, some fish and some insects

47. LE 15-9d The haplo-diploid system Bees & Ants

48. LE 15-9 The X-Y system The X-0 system The Z-W system The haplo-diploid system Parents Sperm Ova Zygotes (offspring)

49. Sex Linked The sex chromosomes can have other genes on them – not related to sex determination A gene located on either sex chromosome is called a sex-linked gene Sex-linked genes follow specific patterns of inheritance

50. Sex Linked Diseases Some disorders caused by recessive alleles on the X chromosome in humans: –Color blindness –Muscular dystrophy (Duchenne MD) –Hemophilia

51. LE 15-10a Sperm Ova

52. LE 15-10b Sperm Ova

53. LE 15-10c Sperm Ova

54. X-Inactivation in Females In mammals, one of the two X chromosomes is randomly inactivated when “embryo” If a female = heterozygous for a gene located on the X chromosome, she will be a mosaic for that character Very little is understood about how this works

55. LE 15-11 Early embryo: X chromosomes Allele for orange fur Cell division and X chromosome inactivation Allele for black fur Active X Inactive X Black fur Orange fur Active X Two cell populations in adult cat:

57. Mutations In non-disjunction, pairs of homologous chromosomes do not separate normally during meiosis As a result: –one gamete receives two chromosomes –the other gamete receives zero

58. LE 15-12 Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n + 1 Number of chromosomes Nondisjunction of homologous chromosomes in meiosis I n + 1n – 1 n + 1n – 1nn Nondisjunction of sister chromatids in meiosis I

59. Abnormalities Aneuploidy = abnormal number of a particular chromosome

60. Trisomy 3n = three copies of a particular chromosome Monosomic = chromosome missing in the zygote (only one present) Polyploidy = is a condition in which an organism has more than two complete sets of chromosomes Tetraploidy = 4n = four sets of chromosomes

63. Chromosome Breaking Apart Breakage = four types of changes in chromosome structure: –Deletion removes a chromosomal segment –Duplication repeats a segment –Inversion reverses a segment within a chromosome –Translocation moves a segment from one chromosome to another

64. LE 15-14a Deletion A deletion removes a chromosomal segment.

65. LE 15-14b Duplication A duplication repeats a segment.

66. LE 15-14c Inversion An inversion reverses a segment within a chromosome.

67. LE 15-14d Reciprocal translocation A translocation moves a segment from one chromosome to another, nonhomologous one.

69. Genetic Disorders Down syndrome is an aneuploid condition that results from three copies of chromosome 21 (Trisomy 21) It affects about 1 / 700 children born in the United States The frequency of Down syndrome increases with the age of the mother (several theories here…)

70. Down’s Syndrome Maternal Age < Risk of chromosomal abnormality Risk of Down’s Syndrome 15-241/5001/1500 25-291/3851/1100 351/1781/350 401/631/100 451/181/25

71. Figure 15-15

72. Sex Chromosome Abnormalities Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable (survivable) monosomy in humans

73. Chromosomal Abnormalities One syndrome, cri du chat (“cry of the cat”), results from a deletion in chromosome 5 A child born with this syndrome is mentally retarded and has a catlike cry; individuals usually die in infancy or early childhood Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

74. LE 15-16 Reciprocal translocation Normal chromosome 9 Normal chromosome 22 Translocated chromosome 9 Translocated chromosome 22 Philadelphia chromosome

75. Exceptions to the Rule There are two normal exceptions to Mendelian genetics One involves genes located: –in the nucleus –involves genes located outside the nucleus

76. Genes located in Organelles Extra-nuclear genes are genes found in organelles in the cytoplasm This depends on the maternal parent because the zygote’s cytoplasm comes from the egg The first evidence of extra-nuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

77. Figure 15-18

78. Genetic Imprinting For a few traits in mammals - the phenotype depends on which parent the trait came from This is called genetic imprinting This involves the silencing of certain genes that are “stamped” with an imprint during gamete production

79. LE 15-17a Normal lgf2 allele (expressed) Normal lgf2 allele (not expressed) Wild-type mouse (normal size) Paternal chromosome Maternal chromosome A wild-type mouse is homozygous for the normal lgf2 allele.

80. LE 15-17b Normal lgf2 allele (expressed) Mutant lgf2 allele (not expressed) Normal size mouse Paternal Maternal Mutant lgf2 allele (expressed) Normal lgf2 allele (not expressed) Dwarf mouse Paternal Maternal When a normal lgf2 allele is inherited from the father, heterozygous mice grow to normal size. But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype.

81. Human Example Depends on whether the deletion is inherited from Mother or Father on chromosome 15q: If deletion in Father’s 15q: (Child inherits both copies of 15q from Mother) –Prader-Willi syndrome: developmental delay, small or undescended testes, obesity (never feel satisfied), short stature, and mild retardation. If deletion in Mother’s 15q (Child inherits both copies of 15q from Father) –Angelman syndrome: seizures, severe mental retardation, inappropriate laughter, and a characteristic face that is small with a large mouth and prominent chin.

82. Angelman’s Syndrome Prader-Willi Syndrome

85. Figure 15-13