Identifying Genes and Defining Alleles

1. Identifying Genes and Defining Alleles Mutant Hunt - independently isolate number of mutants with identical phenotypes - verify mutant phenotype is recessive - establish pure-breeding strain for each How many genes are involved? The same gene for all strains? Different genes for different strains? 1

2. Identifying Genes and Defining Alleles Mutant Hunt Ex. White flowers in plant species with purple flowers Mutant strain 1 - isolated in Australia Mutant strain 2 - isolated in Pennsylvania 2

3. Identifying Genes and Defining Alleles Biochemical basis for white flower color If only one gene involved: (A or a alleles) Enzyme A White pigment Purple pigment If two different genes involved: (Aa and Bb) Enzyme A Enzyme B White White Purple pigment 3

4. Identifying Genes and Defining Alleles Complementation Test - One gene or Two genes? Cross recessive pure-breeding strains with same (or related) phenotype to each other. If F1 progeny are all mutant = one gene (two alleles) If F1 progeny are wild type = two different genes 4

5. Identifying Genes and Defining Alleles Complementation Test - One gene or Two genes? Alleles of the same gene 5

6. Identifying Genes and Defining Alleles Complementation Test - One gene or Two genes? 6

7. Complementation Analysis Independently isolated mutants - all same phenotype Cross in all possible combinations + wild-type offspring (complementation) - mutant offspring How many genes? Which mutants are defective in same gene? 7

8. Multiple Alleles Many different forms of the same gene 8

9. Multiple Alleles Example Cross A x B Anything possible 9

10. Multiple Alleles Example w gene wild-type, white, eosin alleles 10

11. Multiple Alleles 11

12. Multiple Alleles Humans are highly polymorphic Ex. >200 different alleles for cystic fibrosis gene Ex. >390 alleles for human leukocyte antigen (HLA) 12

13. Dominance of Alleles Complete Dominance / Complete Recessiveness Phenotype: Dominant Recessive Genotype: AA, Aa aa Haplo- Sufficient Loss of Function 13

14. Dominance of Alleles Incomplete Dominance (Semidominance) Haplo- insufficient 14

15. Dominance of Alleles Co-dominance 15

16. Dominance of Alleles Sickle cell anemia 16

17. Lethal Genes Dominant lethal: L- (LL or Ll) doesn’t survive, rare Ex. Huntington chorea - neurodegenerative, late onset Recessive lethal: ll homozygotes die Ex. Achondroplastic dwarfism a+a+normal a+ad dwarf ad addie in utero 17

18. Examples of Recessive Lethal Genes Creeper Chickens: Autosomal lethal 18

19. Examples of Recessive Lethal Genes 2:1 ratio 19

20. Subvital Genes Survival of genotype is not as good as normal 20

21. Gene Interactions & Modified Ratios Variations of Mendelian Dihybrid Ratios: Two genes involved A- B- aaB- A-bb aabb 21

22. Gene Interactions & Modified Ratios Comb shapes 22

23. Gene Interactions & Modified Ratios Bateson & Punnett crossed purebreeding chickens How many genes are involved? 23

24. Gene Interactions & Modified Ratios 24

25. Gene Interactions & Modified Ratios 9:3:3:1 25

26. Gene Interactions & Modified Ratios Flower Color in Sweet Peas - Complementation 9:7 ratio 26

27. Gene Interactions & Modified Ratios Fruit shape in summer squash 9:6:1 ratio 27

28. Epistasis One gene masks the expression of another gene aa B- A- B- Recessive Dominant Gene masking other = epistatic Gene being masked = hypostatic 28

29. Recessive Epistasis Ex. Coat color in mice C- color, cc none A- pattern, aa none 9:3:4 ratio 29

30. Recessive Epistasis Ex. Coat color in Labrador retrievers EeBb x EeBb 9/16 black: 3/16 brown:4/16 yellow 30

31. Dominant Epistasis Ex. Fruit color in summer squash 31

32. Dominant Epistasis Ex. Fruit color in summer squash Hypothetical pathway Y- ww yy ww 32

33. Dominant Epistasis Ex. Graying in horses 4 years 7 years 33

34. Gene Interactions: Eye Color in Drosophila bw+ bw st+ st w+ w st+ st w+ w bw+ bw st+ - w+ - bw+ - 34

35. Gene Interactions: Eye Color in Drosophila bw+ bwst+ stw+ w Xbw+ bwst+ stw+ w bw+- st+- w+- bw+- st+- ww bw+- stst w+- bwbwst+- w+- bw+- ststww bwbwst+- ww bwbwstst w+- bwbwststww 35

36. Suppression Second gene blocks mutant phenotype caused by first gene Normal plant - no malvidin; K- malvidin, kk none; D- suppresses K-, dd no suppression 13:3 ratio 36

37. Modifier Gene Second gene affects degree of expression of first gene Ex. dark color versus light color B- black, bb brown D- intense color, dd dilute color 9:3:3:1 ratio 37

38. Duplicate Genes Both genes control the same cellular activity Ex. A1- or A2 - round fruit a1a1 and a2a2 narrow fruit Enz A1 narrow round Enz A2 A1a1 A2a2 x A1a1 A2a2 9/16 A1- A2-: 3/16 A1- a2a2: 3/16 a1a1 A2-: 1/16 a1a1 a2a2 15 : 1 ratio of round : narrow 38

39. Pleiotropic Genes One gene has many effects on the phenotype Ex. Cystic fibrosis - recessive allele, autosomal gene defective calcium transport breathing difficulties digestive problems reproductive deficiencies reduced immunity 39

40. Penetrance Percentage of individuals with certain genotype who express the expected phenotype. brachydactyly 40

41. Expressivity Degree or extent to which a given genotype is expressed. Variations may result from: environment genetic background other factors 41

42. Variable Expressivity Spotting in dogs All have the same genotype 42

43. Variable Expressivity Neurofibromatosis café au lait spots freckling neurofibromas 43

44. Penetrance and Expressivity 44

45. Monogenic vs Quantitative Traits Discontinuous traits Continuous traits aabbccdd AABBCCDD As gene number increases, phenotype distribution approaches normal curve AA Aa aa 45

46. Quantitative Genetics Polygenic - Many genes affect one aspect of phenotype Quantitative traits - each allele of each gene contributes equally Ex. height, weight, skin color 46

47. Quantitative Genetics Two genes contributing to phenotype quantitatively F2 ratio 1:4:6:4:1 47

48. Quantitative Genetics Inheritance of ear length in corn F1 mean = intermediate More variability in F2 48