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?

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

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

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

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

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

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?

8 Multiple Alleles Many different forms of the same gene

9 Multiple Alleles Example Cross A x B Anything possible

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

11 Multiple Alleles

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

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

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

15 Dominance of Alleles Co-dominance

16 Dominance of Alleles Sickle cell anemia

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 + normala + a d dwarfa d a d die in utero

18 Examples of Recessive Lethal Genes Creeper Chickens: Autosomal lethal

19 Examples of Recessive Lethal Genes 2:1 ratio

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

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

22 Gene Interactions & Modified Ratios Comb shapes

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

24 Gene Interactions & Modified Ratios

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

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

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

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

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

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

31 Dominant Epistasis Ex. Fruit color in summer squash

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

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

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

35 Gene Interactions: Eye Color in Drosophila bw + bw st + st w + w X bw + bw st + st w + w bw + - st + - w + - bw + - st + - ww bw + - stst w + - bwbw st + - w + - bw + - stst ww bwbw st + - ww bwbw stst w + - bwbw stst ww

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

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

38 Duplicate Genes Both genes control the same cellular activity Ex. A1- or A2 - round fruit a1a1 and a2a2 narrow fruit Enz A1 narrowround 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

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

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

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

42 Variable Expressivity Spotting in dogs All have the same genotype

43 Variable Expressivity Neurofibromatosis café au lait spots freckling neurofibromas

44 Penetrance and Expressivity

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

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

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

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