1. Biology 2250 Principles of Genetics Announcements Lab 4 Information: B2250 (Innes) webpage Lab 4 Information: B2250 (Innes) webpage download and print before lab. download and print before lab. Virtual fly: log in and practice Virtual fly: log in and practice http://biologylab.awlonline.com/ http://biologylab.awlonline.com/http://biologylab.awlonline.com/

2. Test 2 Thursday Nov. 17 http://webct.mun.ca:8900/ All quizzes on WebCT for Review Office Hours: 1:30 – 2:30 Tue, Wed., Thr or by appointment: 737-4754, dinnes@mun.ca

3. Mendelian Genetics Topics: -Transmission of DNA during cell division -Transmission of DNA during cell division Mitosis and Meiosis Mitosis and Meiosis - Segregation - Segregation - Sex linkage (problem: how to get a white-eyed female) - Sex linkage (problem: how to get a white-eyed female) - Inheritance and probability - Inheritance and probability - Independent Assortment - Independent Assortment - Mendelian genetics in humans - Mendelian genetics in humans - Linkage - Linkage - Gene mapping - Gene mapping -Gene mapping in other organisms (fungi, bacteria) (fungi, bacteria) - Extensions to Mendelian Genetics - Gene mutation - Chromosome mutation (- Quantitative and population genetics) B2900 B2900          

4. Penetrance, expressivity and G X E PURPOSE: To provide a concise review for human cancer risk related to low-penetrance genes and their effects on environmental carcinogen exposure. CONCLUSION: Sporadic cancers are caused by gene- environment interactions rather than a dominant effect by a specific gene or environmental exposure.

5. Mutation Source of genetic variation: Gene Mutation (Phenotypic effects) - somatic, germinal - somatic, germinal Chromosome mutations (Ch. 11 prob. 1, 2) Chromosome mutations (Ch. 11 prob. 1, 2) - structure - structure - number - number

6. Mutation Gene Mutation: a + ------>a Forward mutation a ------>a + Reverse mutation 1. Somatic mutation - not transmitted to progeny - not transmitted to progeny 2. Germinal Mutation - transmitted to next generation - transmitted to next generation

7. Somatic Mutations Petal colour: Rr red rr white Plant genotype: Rr mutation: Rr rr mutation: Rr rr

9. Somatic mutations

10. Germinal mutations AA (blue) mutation mutation Aa  self  aa(white)

11. Mutant Phenotypes MorphologicalLethalBiochemicalResistance Conditional - DTS (David T. Suzuki) (permissive and restrictive conditions) (permissive and restrictive conditions)

12. Mutation Frequency Drosophila eye-colour w +  w 4 x 10 -5 per gamete Humans Hemophilia (X-linked recessive) 4 x 10 -5 per gamete (1 in 25,000) (1 in 25,000) “It is estimated that up to 30% of cases of hemophilia have no known family history. Many of these cases are the result of new mutations. This means that hemophilia can affect any family.”

13. Mutation Frequency Drosophila eye-colour w +  w 4 x 10 -5 per gamete Mutation rate for a particular gene: very low (efficient repair) but, Large number of genes in a genome: mutations occur every generation 4 x 10 -5 x 50,000 genes = 2 mutations

14. Gene Mutation Mutations are rare and random Ultimate source of genetic variation Cancer: Proto-oncogene  oncogene  cancer mutation mutation “…in an oncogene mutation, the activity of the mutant oncoprotein has been uncoupled from its normal regulatory pathway, leading to its continuous unregulated expression.”  tumor growth

15. Chromosome Mutations Gene mutation: detected genetically Chromosome Mutations: detected genetically and cytologically cytologically 1. Structure 1. Structure 2. Number 2. Number

16. Chromosome Mutations 1. Structure Ch. 11 363 – 372 1. Structure Ch. 11 363 – 372 2. Number Ch. 11 p. 350 - 363 2. Number Ch. 11 p. 350 - 363

17. 1. Chromosome Structure Karyotype: 1. size and number 2. centromere position: telocentric telocentric acrocentric acrocentric metacentric metacentric submetacentric submetacentric acentric acentric (lost)

18. Chromosome Structure 3. Heterochromatin pattern - heterochromatin (dark) - heterochromatin (dark) - euchromatin (light) - euchromatin (light) 4. Banding patterns: a) staining Giemsa bands a) staining Giemsa bands b) polytene chromosomes (flies) b) polytene chromosomes (flies)

19. G-bands

20. Paint of Chr-22

21. “Paint”

22. Structural Abnormalities Normal a b c d e f Normal a b c d e f 1. Deletion a c d e f 2. Duplication a b b c d e f 3. Inversion a e d c b f 4. Translocation a b c d j k g h i e f a b c d j k g h i e f

23. Structural Abnormalities 1. Deletions: deletion homozygote---->usually lethal deletion homozygote---->usually lethal deletion heterozygote----> viable deletion heterozygote----> viable deletion loop b (pairing of a c d homologues) a c d homologues) a c d deletion deletion

24. Deletion heterozygote deletion loop

25. Pseudodominance Deletion Heterozygote: deletion loop b (pairing of a c d homologues) + + + homologues) + + + deletion deletion Phenotype: + b + +

26. Deletion Mapping Prune pn

27. Structural Abnormalities Deletion: notch-wing (Drosophila) Phenotype Phenotype Genotype wing survival N + N + normal alive N + N + normal alive N + N notch alive N + N notch alive N N - dead N N - dead (recessive lethal) (recessive lethal)

28. Genetics of Deletions Reduced map distance ( chromosome shortened)Reduced map distance ( chromosome shortened) Recessive lethalRecessive lethal Deletion loop (detected during meiosis)Deletion loop (detected during meiosis)

29. Structural Abnormalities 2. Duplications: tandem duplication tandem duplication a b b c d a b b c d maintain original evolve new maintain original evolve new function function function function

30. deletion Tandem duplication Unequal crossing over

31. Bar Eye Mutation (Dominant)

32. Gene Duplication and Evolution Gene duplication - Evolution of new function Example: Hemoglobin genes - duplication Express in different stages: Express in different stages: embryo – fetus – adult embryo – fetus – adult

33. Hemoglobin: Alpha Beta Gamma ………..

34. Structural Abnormalities 3. Inversions - different gene order - usually viable - usually viable a b c d e f a b e d c f a b e d c f a b c d e f a b c d e f a b e d c f homozygote heterozygote homozygote N N N I I I N N N I I I normal (N) inversion (I) normal (N) inversion (I)

35. Cytological consequences of an Inversion Heterozygote: Inversion Loop a b c d e a d c b e X crossover Inversion Loop Fig. 11-21

36. Cytological consequences of an Inversion Heterozygote: Inversion Loop Cross-over within an inversion dicentric bridge (broken) dicentric bridge (broken) acentric fragment (lost) acentric fragment (lost) deletions deletions

37. Inversion heterozygote with crossing over Fig. 11-22

38. Inversion Heterozygote Reduced recombination frequency Reduced recombination frequency (suppression of crossing over) (suppression of crossing over) Semisterile Semisterile

39. 4. Translocation a b c d j k g h i e f Translocation Heterozygote (meiosis) N1N1N1N1 T2T2T2T2 T1T1T1T1 N2N2N2N2

40. Translocation

41. Translocation Translocation heterozygote heterozygote Fig. 11-24

42. Translocation heterozygote Adjacent segregation T1T1 N1N1 N2N2 T2T2 inviable

43. Translocation heterozygote Alternate segregation T1T1 N1N1 N2N2 T2T2 viable

44. Translocation Change linkage relationships (position effects) (position effects) Change chromosome size Semisterile - unbalanced meiotic products normal aborted Corn Pollen

45. Structural Abnormalities Normal a b c d e f Normal a b c d e f 1. Deletion a c d e f 2. Duplication a b b c d e f 3. Inversion a e d c b f 4. Translocation a b c d j k g h i e f a b c d j k g h i e f

46. Human Chromosomes

47. Mutation Source of genetic variation: Gene Mutation - somatic, germinal - somatic, germinal Chromosome mutations (Ch. 11) Chromosome mutations (Ch. 11) - structure - structure - number - number  

48. Chromosome Mutation (2. changes in number) Euploidy: variation in complete sets of chromosomes chromosomes Aneuploidy: variation in parts of chromosome sets sets

49. Euploidy 1x monoploid (1 set) = n 2x diploid (2 sets) = 2n 3x triploid 4x tetraploid 5x pentaploid polyploid (> 2 sets) 6x hexaploid n = # chromosomes n = # chromosomes in the gametes

51. Polyploids Autopolyploids: within one species Allopolyploids: from different, closely related species related species

52. Polyploids Larger than Diploids

53. Polyploids Triploids: = 3n - problems with pairing during - problems with pairing during meiosis meiosis - unbalanced gametes - unbalanced gametes - usually sterile - usually sterile Applications: seedless fruits, sterile fish Applications: seedless fruits, sterile fish aquaculture aquaculture

54. Formation of Triploids n n n = 3n = 3n n Polarbodies n 2n2n2n2n n

55. Triploids (3x) Why can’t a triploid produce viable gametes ?

56. Fig. 11-5

57. Triploids (3x) x = 1 Gametes

58. Triploids x = 2 Gametes or viable Non-viable

59. Triploids Probability (2x or x gamete) = ( ) ( ) if x = 10 Prob. = 0.002 of viable gametes 1 2 x - 1

60. Autotetraploid

62. Autotetraploid Doubling of chromosomes: 2x----> 4x Even number of chromosomes: normal meiosis 2 2 segregation------> functional gametes 2 2 segregation------> functional gametes

63. Triploid 2n = 42 x = 7 n = 21 2n = 14, n = x = 7 Chromosome sets: A, B, D 7 7 7 hybrid Origin of Wheat Fig. 11-10 2n = 28 n = 14 714 Allopolyploid

64. Polyploidy Plants: speciation Animals: - rare (sex determination) - fish (salmon) - fish (salmon) - parthenogenetic animals - parthenogenetic animals 123 11 22 12 12

65. Plant Polyploids

66. Chromosome Mutation (changes in number) Euploidy: variation in complete sets of chromosomes chromosomes Aneuploidy: variation in parts of chromosome sets sets

67. Aneuploidy Nullisomics (2n - 2) Monosomics (2n - 1) Trisomics (2n + 1)

69. Aneuploidy Nullisomics (2n - 2) - lethal in diploids - lethal in diploids - tolerated in polyploids - tolerated in polyploids Monosomics (2n - 1) - disturbs chromosome balance - disturbs chromosome balance - recessive lethals hemizygous - recessive lethals hemizygous Trisomics (2n + 1) - sex chromosomes vs autosomes - sex chromosomes vs autosomes - size of chromosome - size of chromosome

72. Aneuploidy Non-disjunction: Gametes Meiosis I n + 1 n - 1 Meiosis II n + 1 n - 1 n n x n - 1 ---------> 2n - 1 monosomic n x n + 1 ---------> 2n + 1 trisomic

73. Aneuploidy Humans: (live births) Monosomics - XO Turner syndrome Monosomics - XO Turner syndrome - no known autosomes - no known autosomes Trisomics XXY Klinefelter sterile male Trisomics XXY Klinefelter sterile male XYY fertile male ( X or Y gametes) XYY fertile male ( X or Y gametes) XXX sometimes normal XXX sometimes normal 21 Down 21 Down 18 Edwards syndromes 18 Edwards syndromes 13 Patau 13 Patau

74. G-bands 1318 21 X Y

75. Downs Births per 1000

77. Mutations Causing Death and Disease in Humans % of live births % of live births Gene mutations: 1.2 Chromosome mutations: 0.61

78. Chromosome Mutations (Humans) % of spontaneous abortions % of spontaneous abortions Trisomics 26 % XO 9 % Triploids 9 % Tetraploids 3 % Others 3 % Chromosome 50 % abnormalities abnormalities

79. Chromosome Mutations Comparison of euploidy with aneuploidy Aneuploids more abnormal than euploids: likely due to gene imbalance likely due to gene imbalance Plants more tolerant than animals to aneuploidy and polyploidy (animal sex determination) (animal sex determination)

80. Summary Mutation - gene - chromosome - chromosome (structure, number) (structure, number) Detecting - cytology - phenotype - phenotype Rate of mutation - low Mutation - source of genetic variation - evolutionary change - evolutionary change geneticanalysis

81. Chapter References Recombination, linkage maps Recombination, linkage maps Ch. 6 p. 148 – 165 Prob: 1-5, 7, 8, 10, 11, 14 Extensions to Mendelian Genetics Ch. 14 p. 459 – 473 Prob: 2, 3, 4, 5, 6, 7 Chromosome Mutations Ch. 11 p. 350 – 377 Prob: 1, 2

82. Mendelian Genetics Topics: -Transmission of DNA during cell division -Transmission of DNA during cell division Mitosis and Meiosis Mitosis and Meiosis - Segregation - Segregation - Sex linkage (problem: how to get a white-eyed female) - Sex linkage (problem: how to get a white-eyed female) - Inheritance and probability - Inheritance and probability - Independent Assortment - Independent Assortment - Mendelian genetics in humans - Mendelian genetics in humans - Linkage - Linkage - Gene mapping - Gene mapping -Gene mapping in other organisms (fungi, bacteria) (fungi, bacteria) - Extensions to Mendelian Genetics - Gene mutation - Chromosome mutation            