Outline of major topics

1. Outline of major topics • Allelic actions and interactions • Dominance • how it works • when there is no real dominance • Multiple alleles • Lethal alleles One Gene!

2. Outline of major topics ... • Genic interactions • Metabolic pathways • novel phenotypes • epistasis • (pleiotropy) More than one gene!

3. Outline of major topics ... • Factors affecting phenotype • Genetic factors • Strange genes • Environmental factors

4. Allelic actions: dominance • In general, dominant allele codes for production of functional protein • P --> purple pigment • In general, recessive allele codes for no functional protein • p --> no pigment

5. Allelic actions: dominance ... PP has two alleles coding for purple pigment Pp has one allele coding for purple pigment, one allele coding for nothing pp has no alleles coding for pigment

6. Allelic actions: dominance ... • In many cases, a simple dominant/recessive relationship does not hold • incomplete or co-dominance

7. Incomplete or Co-dominance • If both alleles code for a contrasting functional protein, heterozygote shows a phenotype completely different from either homozygote! • Two different upper case letters used to symbolize the alleles or one letter w/ superscripts

8. Incomplete or Co-dominance ... • Flower color in carnations • R codes for a red pigment • W codes for a white pigment • RR gives a red flower • WW gives a white flower • RW gives a pink flower

9. R W R W Incomplete or Co-dominance ... Phenotypic ratios = genotypic ratios Pink X Pink --> 1/4 Red, 1/2 Pink, 1/4 White RR RW RW WW

10. Incomplete or Co-dominance ... Andalusian fowl: black X black --> black white X white --> white (blue) black X white --> gray gray X gray --> ?

11. Incomplete or Co-dominance ... • heterozygote shows a BLEND: alleles are incompletely dominant • heterozygote shows BOTH: alleles are co-dominant

12. Incomplete or Co-dominance ... MN Blood grouping (Landsteiner and Levine) two alleles: M - produces M antigens N - produces N antigens

13. M M M M N M M N N N N N Incomplete or Co-dominance ... Genotypes: Phenotypes: MM MN NN Type M; has only M antigens (Anti-N antibodies) Type MN; has both antigens (no antibodies) Type N; has only N antigens (Anti-M antibodies)

14. Incomplete or Co-dominance ... • Incomplete dominance = co-dominance • Just label differently depending on whether phenotype shows BLENDING • Mechanism generally the same; both alleles code for a working protein

15. Multiple alleles • May be > just two choices of alleles at one locus • Population level phenomenon; individuals have, at most, two different alleles (heterozygous)

16. Multiple alleles ... ABO Blood Groupings Four possible blood types (phenotypes): A B AB O Controlled by one gene

17. ABO Blood Groupings ... Three alleles, with co-dominance as well as as dominant/recessive relationship Alleles: A, B, O (or IA IB IO) Phenotype (blood type) is a result of the proteins coded for by each allele

18. ABO Blood Groupings ... A codes for A antigen B codes for B antigen O codes for no antigen

19. ABO Blood Groupings ... AA AO Type A: A antigens; anti-B antibodies BB BO Type B: B antigens; anti-A antibodies AB Type AB: A & B antigens; no antibodies Type O: no antigens; anti-A and anti-B antibodies OO

20. ABO Blood Groupings ... • O is recessive to both A and B • A and B are co-dominant • Blood type AB is considered the “universal recipient” • no antibodies produced • Blood type O is considered the “universal donor” • no antigens produced

21. Reminders ... • Dominance is not an inherent property of an allele • An allele may be dominant to a second allele, but co-dominant, incompletely dominant, or even recessive to a third

22. Coat color in rabbits Four alleles: c+ cch ch ca agouti chinchilla Himalayan albino c+ is dominant to all others cch is incompletely dominant to ch and ca ch is dominant to ca

23. Coat color in rabbits ... c+ __  agouti cch cch  chinchilla cch ca  light gray cch ch  light gray w/dark tips ch ch or chca  Himalayan ca ca  albino

24. Multiple alleles ... • Many, if not most, genes do have multiple possible alleles • Rhesus blood group (+ or -) • actually at least 18 alleles • One white eye locus in Drosophila • over 100 alleles

25. Lethal alleles • First described by Cuenot in 1905 • coat color in mice • strain with yellow coats • yellow dominant to wild-type agouti • could not produce true-breeding (homozygous) yellows

26. Lethal alleles ... • Each time Cuenot crossed two yellow mice, 1/3 of the offspring were agouti • Backcrossed yellow mice to agouti, saw all yellow mice were heterozygotes • Impossible to produce homozygous yellow mice!

27. Lethal alleles ... • Castle and Little offered explanation: • yellow allele dominant w/ respect to coat color • yellow allele also a recessive lethal allele • homozygous yellows die as embryos

28. c+ cy c+ cy c+c+ cyc+ cyc+ cycy Lethal alleles ... Yellow X Yellow cy c+ cy c+ cycy do not live to birth Apparent ratio: 2/3 yellow : 1/3 agouti

29. Lethal alleles ... • Mechanisms of lethality • recessive lethals: not coding for some necessary product • Hemophilia: dominant allele --> clotting factor recessive allele -> no clotting factor • Sickle cell anemia: S --> normal hemoglobin s --> abnormal hemoglobin

30. Lethal alleles ... • Mechanisms of lethality … • Dominant lethals: very rare. Gene product itself causes death • Huntington’s disease: H --> type of neurotoxin h --> no neurotoxin • Retinoblastoma: R --> allows tumor formation r --> no tumor formation

31. Lethal alleles ... • Once again, note that “dominance” in itself means nothing. • Refers only to phenotype that appears in the heterozygote • Lethals may be dominant with respect to one phenotype and recessive with respect to the lethal action

32. Genic interactions • Two or more genes acting on one trait • Novel phenotypes • Epistasis • One gene acting on more than one trait • Pleiotropy ***All due to metabolic pathways***

33. Genic interactions: Novel Phenotypes Eye color in Drosophila P: red eyed x white eyed F1: red eyed F2: red eyed white eyed 9 3 3 1 brown eyed scarlet eyed

34. Genic interactions: Novel Phenotypes S = wild-type (red) s = scarlet B = wild-type (red) b = brown S __ B __ -->wild-type (red) S __ bb -->brown eyes ss B __ -->scarlet eyes ss bb -->white eyes

35. RED Genic interactions: Novel Phenotypes The S allele controls the production of BROWN pigment The B allele controls the production of SCARLET pigment Cpd. Y ---enzyme S---> BROWN Cpd. X ---enzyme B---> SCARLET

36. Genic interactions: Novel Phenotypes Poultry: comb shape Two genes, w/ 2 alleles each: pea vs. single, and rose vs. single Considered separately: AA, Aa = pea BB, Bb = rose aa = single bb = single

37. Genic interactions: Novel PhenotypesPoultry comb shapes ... The genotype at each of 2 loci plays a role in determining comb shape: A__ B__ = walnut aa B__ = rose A__ bb = pea aa bb = single

38. Genic interactions: Epistasis • One gene masks a second gene • Due to a linear, instead of branched, metabolic pathway

39. Genic interactions: EpistasisCoat color in mice B = agouti b = black A = non-albino a = albino A__ B__ = agouti A__ bb = black aa __ __ = albino

40. black pigment Colorless precursor enzyme A agouti pattern enzyme B Genic interactions: EpistasisCoat color in mice ...

41. AB agouti • Ab black • (3 aB + 1 ab) white Genic interactions: EpistasisCoat color in mice ... Aa Bb X Aa Bb:

42. Epistasis: Coat color in Labs B = black b = chocolate E = black or chocolate e = yellow Black Chocolate Yellow Yellow E__ B__ E__ bbee B __ ee bb

43. Aa Bb x Aa Bb Genic interactions: Epistasis Fruit color in summer squash aa bb = green aa B__ = yellow A__ __ __ = white

44. How can we distinguish allelic interactions from genic interactions? • While the F2 ratios will not follow basic Mendelian rules, they still provide information • Allelic interaction (one gene) will lead to a deviant 3:1 • 1:2:1 most likely • Genic interaction (2 genes) will lead to a deviant 9:3:3:1 • 9:3:4 12:3:1 9:6:1 9:7 • 3 genes: deviant 27:9:9:9:3:3:3:1

45. Pleiotropy • One gene may affect more than one trait • This is again due to the metabolic pathways involved

46. Pleiotropy • PKU - phenylketonuria • P codes for phenylalanine hydroxylase • enzyme metabolizes phenylalanine • p does not code for functional enzyme • phenylalanine cannot be metabolized • primary result: mental retardation • also affects head size, skin/hair/eye color, “mousy” odor, peculiarities of gait, stance, sitting posture, eczema, epilepsy

47. Pleiotropy: PKU metabolic pathway protein phenylpyruvic acid (PKU) phenylalanine phenylalanine hydroxylase tyrosine transaminase melanin

48. Other factors affecting phenotype • Overview • Genetic factors • Incomplete penetrance • Variable expressivity • Sex limited and sex influenced traits • Environmental factors • Nutrition, light, temperature, etc.....

49. Incomplete Penetrance and Variable Expressivity • Incomplete penetrance • Identical genotypes differ in phenotype • Penetrance = % individuals w/ genotype expressing the associated phenotype • Variable expressivity • Variation in the degree of expression of the phenotype

50. Incomplete Penetrance Eye shape in Drosophila Lobe locus: dominant allele which reduces the size of the eye LL Ll ll reduced eye normal eye