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. Quiz – 3 answers 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)         

4. Linkage: Summary Recombination: generates new combinationsRecombination: generates new combinations (inter and intrachromosomal) (inter and intrachromosomal) Genetic maps:Genetic maps: - genes linked on the same chromosome - genes linked on the same chromosome - location of new genes relative to genes - location of new genes relative to genes already mapped already mapped

5. Linkage: Summary Hunting for genes (Human Diseases)Hunting for genes (Human Diseases) - genetic markers: DNA variation - genetic markers: DNA variation - co-inheritance with diseases using pedigree - co-inheritance with diseases using pedigree information information - recombinants used to estimate linkage - recombinants used to estimate linkage

6. Extensions to Mendelian Genetics Ch. 14 From Gene to Phenotype Readings: Ch. 14 p. 454 – 473 Problems: Ch. 14: 2, 3, 4, 5, 6, 7

7. Chapter 1 Genes, environment, organism Phenotype = Phenotype = gene + env. + gene x env. + gene x gene gene + env. + gene x env. + gene x gene Mendelian Genetics: Genotype Phenotype Genotype Phenotype Dominance ? Dominance ?

8. G x E interaction

9. Extensions to Mendelian Genetics (Gene  Phenotype) 1. Dominance 2. Multiple alleles 3. Pleiotropy 4. Epistasis (gene interaction) 5. Penetrance and expressivity

10. Gene interaction 1.Alleles at one gene Dominance 2.Different genes Epistasis

11. 1. Dominance Location of heterozygote between two homozygotes 1. Complete 1. Complete 2. No dominance 2. No dominance 3. Incomplete (partial) 3. Incomplete (partial) 4. Codominance 4. Codominance

12. Homozygotes: A 1 A 1 A 2 A 2 Heterozygote: A 1 A 2

13. Incomplete Dominance redwhite pink

14. Codominance Human Blood Groups: Human Blood Groups: Genotype Phenotype ** AA A AA A AB AB co-dominance AB AB co-dominance BB B BB B ** antigen protein on RBC

15. Codominance Molecular Markers Molecular Markers AB AA BB BB AB Allele Heterozygote distinguished from homozygotes

16. 2. Multiple Alleles (ABO Blood groups - 3 alleles ) Genotype Phenotype (6) (4) (6) (4)--------------------------------------------- OO O recessive OO O recessive AA, AO A dominant BB, BO B dominant AB AB co-dominant AB AB co-dominant---------------------------------------------

17. Multiple alleles in clover

18. Test for Allelism Possibilities: 1. alleles for the same gene - all crosses show Mendelian ratios (1:1 3:1 1:2:1) Mendelian ratios (1:1 3:1 1:2:1) 2. more complex inheritance (> 1 gene) or

19. Example: white, yellow, pink Example: white, yellow, pink Cross F 1 F 2 Cross F 1 F 2 white x yellow yellow 3:1 yellow : white white x pink pink 3:1 pink : white yellow x pink pink 3:1 pink : yellow 3 alleles: w y p 3 alleles: w y p 6 genotypes: w w y y p p p w y w y p 6 genotypes: w w y y p p p w y w y p

20. 3. Pleiotropy (one gene affects > 1 trait) Example: Mouse Gene affects: Gene affects: 1. coat colour (, yellow) 1. coat colour (, yellow) 2. survival 2. survival AA AA Homozygous wildtype dark

21. YellowParents zzz

22. Crosses A. x -----> all A. x -----> all B. x ---> 1/2 1/2 B. x ---> 1/2 1/2 C. x ----> 2/3 1/3 C. x ----> 2/3 1/3

23. Explanation A. AA x AA all AA B. AA x A Y A ½ A Y A, ½ AA C. A Y A x A Y A ¼ AA ½ A Y A ¼ A Y A Y dies 1 : 2 1 : 2 1/3 2/3 1/3 2/3

24. Interpretation Gene affects both coat colour and survival survival 1. A Y dominant to A for coat colour 2. A Y recessive lethal for survival

25. Pleiotropy Phenotype Phenotype Genotype coat colour survival Genotype coat colour survival A A dark alive A A dark alive A A Y yellow alive A A Y yellow alive A Y A Y ? dead A Y A Y ? dead dark

26. Pleiotropy Gene A Trait 1 Trait 1 Trait 2 Trait 2 Epistasis Gene A Trait Trait Gene B G + E = P Gene interaction

27. 4. Epistasis (gene interaction) More than one gene affects a character One gene pair masks or modifies the expression of another gene pair AABB x aabb ----> AaBb x AaBb ---> F 2 AABB x aabb ----> AaBb x AaBb ---> F 2 F 1 F 1Dihybrid

28. F2F2F2F2 AaBb x AaBb A- B- 9/16 A- bb 3/16 aa B- 3/16 aa bb 1/16 4 distinct phenotypes (2 traits) (peas: shape, colour) Epistasis: Gene A and Gene B interact  phenotype of 1 trait Gene A and B unlinked Epistasis

29. Epistasis (BbEe X BbEe) Labrador retriever Coat Colour (B and E genes) F 2 Ratio Genotype Phenotype Ratio 9/16 B- E- black 9/16 3/16 B- ee gold 4/16 3/16 bb E- brown 3/16 1/16 bb ee gold Gene E allows colour deposition Gene E allows colour deposition 1.

30. Allele E Allele B Allele E Allele B Golden brown black B- ee bb E- B- E- B- ee bb E- B- E- bb ee bb ee Epistasis

31. Epistasis (AaBb X AaBb) Example: Flower petal colour F 2 Ratio Genotype Phenotype Ratio 9/16 A- B- Purple 9/16 3/16 A- bb White 7/16 3/16 aa B- White 1/16 aa bb White 2.

32. Gene B Gene A Gene B Gene A colourless colourless purple (white) (white) A-bb aaB- A- B- aabb

33. 5. Penetrance and Expressivity Phenotype: genotype, genetic background, and environment and environment Variable Expression: Penetrance Expressivity Expressivity

34. Penetrance: Penetrance: percentage of individuals that show some degree of expression of a mutant genotype percentage of individuals that show some degree of expression of a mutant genotype

35. Example: Polydactyly (P) extra digits pp Pp PP pp Pp PP normal 10 % normal polydactyly 90 % polydactyly 90 % polydactyly

36. Expressivity: degree that a given genotype is expressed phenotypically Expressivity: degree that a given genotype is expressed phenotypically Example: Pp individuals which do express the extra digits can vary the extra digits can vary (a) extra digit on each hand and foot (a) extra digit on each hand and foot (b) extra digit on one hand only (b) extra digit on one hand only (c) complete digit or vestige (c) complete digit or vestige

37. Same genotype

38. Variable expressivity of piebald spotting in beagles

39. Summary - segregation and independent assortment can explain a variety of patterns of can explain a variety of patterns of genetic variation genetic variation -Phenotype = Genotype + Environment Genetic interaction: genotype, epistasis, Genetic interaction: genotype, epistasis, genetic background genetic background

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

41. 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

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

44. Somatic mutations

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

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

47. 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.”

48. 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

49. Gene Mutation Mutations are rare and random Ultimate source of genetic variation Cancer: Proto-oncogene  oncogene  cancer mutation mutation

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

51. 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

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

53. 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)

54. G-bands

55. Paint of Chr-22

56. “Paint”

57. 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

58. 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

59. Deletion heterozygote deletion loop

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

61. Deletion Mapping Prune pn

62. 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)

63. 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)

64. 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

65. deletion Tandem duplication Unequal crossing over

66. Bar Eye Mutation (Dominant)

67. 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

68. Hemoglobin: Alpha Beta Gamma ………..

69. 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)

70. 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

71. 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

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

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

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

75. Translocation

76. Translocation Translocation heterozygote heterozygote Fig. 11-24

77. Translocation heterozygote Adjacent segregation T1T1 N1N1 N2N2 T2T2 inviable

78. Translocation heterozygote Alternate segregation T1T1 N1N1 N2N2 T2T2 viable

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

80. 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