2. Chapter 14 Draw 13 boxes on your paper

3. Probability & genetics Calculating probability of making a specific gamete is just like calculating the probability in flipping a coin – probability of tossing heads? – probability making a B gamete? 50% 100% BB B B Bb B b

4. Probability & genetics Outcome of 1 toss has no impact on the outcome of the next toss – probability of tossing heads each time? – probability making a B gamete each time? 50% Bb B b

5. Calculating probability Pp x Pp spermegg 1/2 offspring =x1/4 PPPP PpPpPp 1/2 =x1/4 pppp pP Pp male / sperm P p female / eggs PPPpPp PpPppp 1/2 =x1/4 1/2 =x 1/4 1/2 +

6. Rule of multiplication Chance that 2 or more independent events will occur together – probability that 2 coins tossed at the same time will land heads up – probability of Pp x Pp  pp 1/2 x 1/2 = 1/4 PpPp P p

7. Calculating probability in crosses Use rule of multiplication to predict crosses YyRr x yyrr ?% Yy x Rr x 1/4 1/16 yyrr x

8. Apply the Rule of Multiplication Got it? Try this! AABbccDdEEFfAaBbccDdeeFfx AabbccDdEeFF Bb x Bb  bb cc x cc  cc Dd x Dd  Dd EE x ee  Ee Ff x Ff  FF AA x Aa  Aa 1/2 1/4 1 1/2 1 1/4 1/64

9. Rule of addition Chance that an event can occur 2 or more different ways – sum of the separate probabilities – probability of Bb x Bb  Bb spermeggoffspring 1/2 =x1/4 BbBb 1/2 =x1/4 bBBb 1/4 + 1/2

10. Box #1 How are probability and genetics related?

11. Pedigree analysis Pedigree analysis reveals Mendelian patterns in human inheritance – data mapped on a family tree = male= female= male w/ trait = female w/ trait

12. Genetic counseling Pedigree can help us understand the past & predict the future Thousands of genetic disorders are inherited as simple recessive traits – from benign conditions to deadly diseases – albinism – cystic fibrosis – Tay sachs – sickle cell anemia – PKU

13. Genetic testing

14. Recessive diseases The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all – Heterozygotes (Aa) carriers have a normal phenotype because one “normal” allele produces enough of the required protein

15. Box#2 solve the following problem in box #2: In purple people eaters, one-horn is dominant and no horns is recessive. Show the cross of a purple people eater that is heterozygous for horns with a purple people eater that does not have horns. Summarize the genotypes and phenotypes of the possible offspring.

16. Box #3 answer the following questions in box #3 In humans, curly hair is dominant over straight hair. A woman heterozygous for hair curl marries a man with straight hair and they have children. 1.What is the genotype of the mother? 2.What gametes can she produce? 3.What gametes can the father produce? 4.What is the probability that the 1 st child will have curly hair? 5.What is the probability the 2 nd child will have curly hair?

17. Box#4 What is the probability of each of the following sets of parents producing the given genotypes in their offspring? Parents Genotype Offspring Genotype Probability Aa x AaAa Aa x aaAa AaBb x AaBBAABB AaBb x AABbAabb AaBb x AaBbAaBb

18. Heterozygote crosses Heterozygotes as carriers of recessive alleles Aa x Aa Aa male / sperm A a female / eggs AA Aaaa Aa A a A a AAAaaaAa

19. Cystic fibrosis Primarily people of European descent – strikes 1 in 2500 births 1 in 25 people of European descent is a carrier (Aa) – normal allele codes for a membrane protein that transports Cl - across cell membrane defective or absent channels limit transport of Cl - (& H 2 O) across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections – without treatment children die before 5; with treatment can live past their late 20s normal lung tissue

20. Normal Lungs Chloride channel Transports chloride through protein channel out of cell Osmotic effects: H 2 O follows Cl - airway cells lining lungs Cl - Na + mucus secreting glands

21. Cystic fibrosis airway cells lining lungs Cl - Na + bacteria & mucus build up thickened mucus hard to secrete damaged lung tissue

23. Tay-Sachs Primarily Jews of eastern European (Ashkenazi) descent & Cajuns – strikes 1 in 3600 births 100 times greater than incidence among non-Jews or Mediterranean (Sephardic) Jews – non-functional enzyme fails to breakdown lipids in brain cells symptoms begin few months after birth seizures, blindness & degeneration of motor & mental performance child usually dies before 5yo

24. Sickle cell anemia Primarily Africans – strikes 1 out of 400 African Americans – caused by substitution of a single amino acid in hemoglobin – when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods deforms red blood cells into sickle shape sickling creates pleiotropic effects = cascade of other symptoms

25. Sickle cell anemia Substitution of one amino acid in polypeptide chain

27. Sickle cell phenotype 2 alleles are codominant – both normal & mutant hemoglobins are synthesized in heterozygote (Aa) – carriers usually healthy, although some suffer some symptoms of sickle-cell disease under blood oxygen stress exercise

28. Heterozygote advantage Sickle cell frequency – high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes 1 out of 400 African Americans Suggests some selective advantage of being heterozygous – sickle cell: resistance to malaria? – cystic fibrosis: resistance to cholera?

29. Heterozygote advantage Malaria – single-celled eukaryote parasite spends part of its life cycle in red blood cells In tropical Africa, where malaria is common: – homozygous dominant individuals die of malaria – homozygous recessive individuals die of sickle cell anemia – heterozygote carriers are relatively free of both High frequency of sickle cell allele in African Americans is vestige of African roots

30. Malaria

31. Prevalence of Malaria Prevalence of Sickle Cell Anemia

32. Huntington’s chorea Dominant inheritance – on end of chromosome 4 one of 1 st genes to be identified mutation = CAG repeats = glutamine amino acid – build up of protein “huntingtin” in neurons (brain) causing cell death memory loss muscle tremors, jerky movements = “chorea” early death (10-20 years after onset) – onset age 30-50 1872

33. Genetics & culture Why do all cultures have a taboo against incest? – laws or cultural taboos forbidding marriages between close relatives are fairly universal Fairly unlikely that 2 unrelated carriers of same rare harmful recessive allele will meet & mate – but matings between close relatives increase risk “consanguineous” (same blood) matings – individuals who share a recent common ancestor are more likely to carry same recessive alleles

34. AAAaaaAa A hidden disease reveals itself AA x Aa AA male / sperm A a female / eggs AaAAAaAAAa x Aa male / sperm A a female / eggs AAAaaaAa

35. Box #5 What is the heterozygote advantage?

36. Beyond Mendel’s Laws of Inheritance

37. Extending Mendelian genetics Mendel worked with a simple system – peas are genetically simple – most traits are controlled by a single gene – each gene has only 2 alleles, 1 of which is completely dominant to the other The relationship between genotype & phenotype is rarely that simple

38. Incomplete dominance Heterozygote shows an intermediate, blended phenotype – example: RR = red flowers rr = white flowers Rr = pink flowers – make 50% less color RRRrrr

39. Incomplete dominance true-breeding red flowers true-breeding white flowers X P 100% 100% pink flowers F 1 generation (hybrids) self-pollinate 25% white F 2 generation 25% red 1:2:1 50% pink It’s like flipping 2 pennies!

40. Incomplete dominance C R C W x C R C W CRCR CWCW male / sperm CRCR CWCW female / eggs _____ ____ 1:2:1 ____ 1:2:1 % genotype % phenotype CRCRCRCR CRCWCRCW CRCWCRCW CWCWCWCW ____ _____

41. Box #6 Certain breeds of cattle show incomplete dominance in coat color. When pure breeding red cows are bred with pure breeding white cows, the offspring are roan (a pinkish coat color). Summarize the genotypes and phenotypes of the possible offspring when a roan cow is mated with a roan bull.

42. Box #7 Cows also have a second gene for horn vs hornless cattle. The allele for horns dominates the allele for hornless. If a bull and cow are heterozygous for both genes, what are the probabilities for each possible phenotype?

43. Co-dominance 2 alleles affect the phenotype equally & separately – not blended phenotype – example: ABO blood groups – 3 alleles I A, I B, i I A & I B alleles are co-dominant to each other – both antigens are produced both I A & I B are dominant to i allele – produces glycoprotein antigen markers on the surface of red blood cells

47. Box #8 What is incomplete dominance? What is co-dominance?

48. Box #9 A man with type AB blood marries a woman with type B blood. Her mother has type O blood. List the expected phenotype and genotype frequencies of their children.

49. Pleiotropy Most genes are pleiotropic – one gene affects more than one phenotypic character wide-ranging effects due to a single gene dwarfism (achondroplasia) gigantism (acromegaly)

50. Acromegaly: André the Giant

51. Epistasis one gene will mask the expression of another gene – coat color in mice = 2 separate genes C,c: pigment (C) or no pigment (c) B,b: more pigment (black=B) or less (brown=b) cc = albino, no matter B allele 9:3:3:1 becomes 9:3:4 How would you know that difference wasn ’ t random chance? Chi-square test!

52. Epistasis in Labrador retrievers 2 genes: (E,e) & (B,b) – pigment (E) or no pigment (e) – pigment concentration: black (B) to brown (b) E–B–E–bbeeB–eebb

53. Box #10 make up an example of epistasis

54. Polygenic inheritance Some phenotypes determined by additive effects of 2 or more genes on a single character – phenotypes on a continuum – human traits skin color height weight eye color intelligence behaviors

55. Box #11 describe in your own words, polygenic inheritance.

56. enzyme Skin color: Albinism However albinism can be inherited as a single gene trait Johnny & Edgar Winter albino Africans melanin = universal brown color tyrosine melanin albinism

57. OCA1 albinoBianca Knowlton

58. Sex linked traits Genes are on sex chromosomes – as opposed to autosomal chromosomes – first discovered by T.H. Morgan at Columbia U. – Drosophila breeding good genetic subject – prolific – 2 week generations – 4 pairs of chromosomes – XX=female, XY=male 1910 | 1933

59. autosomal chromosomes sex chromosomes Classes of chromosomes

60. Huh! Sex matters?! F 2 generation 100% red-eye female 50% red-eye male 50% white eye male Discovery of sex linkage P X F 1 generation (hybrids) 100% red eye offspring true-breeding white-eye male true-breeding red-eye female

61. Genetics of Sex In humans & other mammals, there are 2 sex chromosomes: X & Y – 2 X chromosomes develop as a female: XX gene redundancy, like autosomal chromosomes – an X & Y chromosome develop as a male: XY no redundancy 50% female : 50% male

62. box# #12 The genes for hemophilia are located on the X chromosome. It is a recessive disorder. List the possible genotypes and phenotypes of the children from a man normal for blood clotting and a woman who is a carrier. (Hint: you have to keep track of what sex the children are).

63. Genes on sex chromosomes Y chromosome – few genes other than SRY sex-determining region master regulator for maleness turns on genes for production of male hormones – many effects = pleiotropy! X chromosome – other traits beyond sex determination mutations: – hemophilia – Duchenne muscular dystrophy – color-blindness

64. Human X chromosome Sex-linked – usually means “X-linked” – more than 60 diseases traced to genes on X chromosome

65. Map of Human Y chromosome? < 30 genes on Y chromosome Sex-determining Region Y ( SRY ) Channeling Flipping ( FLP ) Catching & Throwing ( BLZ-1) Self confidence ( BLZ-2) note: not linked to ability gene Devotion to sports ( BUD-E) Addiction to death & destruction movies ( SAW-2) Scratching ( ITCH-E) Spitting ( P2E) linked Inability to express affection over phone ( ME-2) Selective hearing loss ( HUH) Total lack of recall for dates ( OOPS) Air guitar ( RIF)

66. Sex-linked traits summary X-linked – follow the X chromosomes – males get their X from their mother – trait is never passed from father to son Y-linked – very few genes / traits – trait is only passed from father to son – females cannot inherit trait

74. X-inactivation Female mammals inherit 2 X chromosomes – one X becomes inactivated during embryonic development condenses into compact object = Barr body which X becomes Barr body is random – patchwork trait = “mosaic” XHXhXHXh XHXHXhXh

75. X-inactivation & tortoise shell cat 2 different cell lines in cat

76. Box #13 Why does X inactivation exists in females and not males?

77. Male pattern baldness Sex influenced trait – autosomal trait influenced by sex hormones age effect as well = onset after 30 years old – dominant in males & recessive in females B_ = bald in males; bb = bald in females

78. Nature vs. Nurture Phenotype is controlled by both environment & genes Color of Hydrangea flowers is influenced by soil pH Human skin color is influenced by both genetics & environmental conditions Coat color in arctic fox influenced by heat sensitive alleles