1. Mendel and the Gene Idea

2. Inheritance u The passing of traits from parents to offspring. u Humans have known about inheritance for thousands of years.

3. Genetics u The scientific study of the inheritance. u Genetics is a relatively “new” science (about 150 years).

4. Gregor Mendel u Father of Modern Genetics.

6. u Mendel was a pea picker. u He used peas as his study organism.

7. Why Use Peas? u Short life span. u Bisexual. u Many traits known. u Cross- and self-pollinating. u (You can eat the failures).

8. Cross-pollination u Two parents. u Results in hybrid offspring where the offspring may be different than the parents.

10. Self-pollination u One flower as both parents. u Natural event in peas. u Results in pure-bred offspring where the offspring are identical to the parents.

11. Mendel's Work u Used seven characters, each with two expressions or traits. u Example: u Character - height u Traits - tall or short.

17. Another Sample Cross P1 Tall X short (TT x tt) F1 all Tall (Tt) F2 3 tall to 1 short (1 TT: 2 Tt: 1 tt)

19. PLANT HEIGHT u Mendel noticed that tall peas crossed with short peas yielded all tall peas in the F1 generation (first group of offspring) TALL X SHORT ALL TALL

22. PLANT HEIGHT u Mendel now took the F1 peas and crossed them with themselves to produce an F2 generation (2nd group of offspring) u This produced tall and short offspring in a 3 tall to 1 short ratio

24. Results - Summary  In all crosses, the F1 generation showed only one of the traits regardless of which was male or female. u The other trait reappeared in the F2 at ~25% (3:1 ratio).

25. Mendel's Hypothesis 1. Genes can have alternate versions called alleles. 2. Each offspring inherits two alleles, one from each parent.

26. Mendel's Hypothesis 3. If the two alleles differ, the dominant allele is expressed. The recessive allele remains hidden unless the dominant allele is absent.

27. Mendel's Hypothesis 4. The two alleles for each trait separate during gamete formation. This now called: Mendel's Law of Segregation

28. Law of Segregation

32. Vocabulary u Phenotype - the physical appearance of the organism. u Genotype - the genetic makeup of the organism, usually shown in a code. u T = tall u t = short

34. Helpful Vocabulary u Homozygous - When the two alleles are the same (TT/tt). u Heterozygous- When the two alleles are different (Tt).

35. STEPS For WORKING A GENETICS PROBLEM u Assign symbols for alleles u Determine the parents’ GENOTYPES u Determine the kinds of GAMETES u Look at all possible combinations of gametes: PUNNETT SQUARE u Determine the possible offspring PHENOTYPES

36. More Practice: Paternity Case u Who's Your Daddy? Who's Your Daddy?

37. 6 Mendelian Crosses are Possible Cross Genotype Phenotype TT X tt all Tt all Dom Tt X Tt 1TT:2Tt:1tt 3 Dom: 1 Res TT X TT all TT all Dom tt X tt all tt all Res TT X Tt 1TT:1Tt all Dom Tt X tt 1Tt:1tt 1 Dom: 1 Res

38. Test Cross u Cross of a suspected heterozygote with a homozygous recessive. u Ex: T_ X tt If TT - all dominant If Tt - 1 Dominant: 1 Recessive

40. Dihybrid Cross u Cross with two genetic traits. u Need 4 letters to code for the cross. u Ex: TtRr u Each Gamete - Must get 1 letter for each trait. u Ex. TR, Tr, etc.

41. u Incomplete Dominance / Codominance Incomplete Dominance / Codominance

42. Number of Kinds of Gametes u Critical to calculating the results of higher level crosses. u Look for the number of heterozygous traits.

43. Equation The formula 2 n can be used, where “n” = the number of heterozygous traits. Ex: TtRr, n=2 2 2 or 4 different kinds of gametes are possible. TR, tR, Tr, tr

44. Dihybrid Cross TtRr X TtRr Each parent can produce 4 types of gametes. TR, Tr, tR, tr Cross is a 4 X 4 with 16 possible offspring.

45. Results u 9 Tall, Red flowered u 3 Tall, white flowered u 3 short, Red flowered u 1 short, white flowered Or: 9:3:3:1

46. Law of Independent Assortment u The inheritance of 1st genetic trait is NOT dependent on the inheritance of the 2 nd trait. u Inheritance of height is independent of the inheritance of flower color.

48. Comment u Ratio of Tall to short is 3:1 u Ratio of Red to white is 3:1 u The cross is really a product of the ratio of each trait multiplied together. (3:1) X (3:1)

49. Probability u Genetics is a specific application of the rules of probability. u Probability - the chance that an event will occur out of the total number of possible events.

51. Genetic Ratios u The monohybrid “ratios” are actually the “probabilities” of the results of random fertilization. Ex: 3:1 75% chance of the dominant 25% chance of the recessive

52. Rule of Multiplication u The probability that two alleles will come together at fertilization, is equal to the product of their separate probabilities.

53. Example: TtRr X TtRr u The probability of getting a tall offspring is ¾. u The probability of getting a red offspring is ¾. u The probability of getting a tall red offspring is ¾ x ¾ = 9/16

54. Comment u Use the Product Rule to calculate the results of complex crosses rather than work out the Punnett Squares. u Ex: TtrrGG X TtRrgg

55. Solution “T’s” = Tt X Tt = 3:1 “R’s” = rr X Rr = 1:1 “G’s” = GG x gg = 1:0 Product is: (3:1) X (1:1) X (1:0 ) = 3:3:1:1

56. Tips for Dihybrid Problems u Identify all of the alleles that can be identified from the phenotypes of the parents or kids. u Work from the monohybrid ratios to solve for the missing alleles.

57. Variations on Mendel 1. Incomplete Dominance 2. Codominance 3. Multiple Alleles 4. Epistasis 5. Polygenic Inheritance

58. Incomplete Dominance u When the F1 hybrids show a phenotype somewhere between the phenotypes of the two parents. Ex. Red X White snapdragons F1 = all pink F2 = 1 red: 2 pink: 1 white

60. Result u No hidden Recessive. u 3 phenotypes and 3 genotypes (Hint! – often a “dose” effect) u Red = C R C R u Pink = C R C W u White = C W C W

61. Another example

62. Codominance u Both alleles are expressed equally in the phenotype. u Ex. MN blood group u MM u MN u NN

63. Result u No hidden Recessive. u 3 phenotypes and 3 genotypes (but not a “dose” effect)

64. Multiple Alleles u When there are more than 2 alleles for a trait. u Ex. ABO blood group u I A - A type antigen u I B - B type antigen u i - no antigen

65. Result u Multiple genotypes and phenotypes. u Very common event in many traits.

66. Alleles and Blood Types Type Genotypes A I A I A or I A i B I B I B or I B i AB I A I B O ii

69. Comment u Rh blood factor is a separate factor from the ABO blood group. u Rh+ = dominant u Rh- = recessive u A+ blood = dihybrid trait

70. Epistasis u When 1 gene locus alters the expression of a second locus. u Ex: u 1 st gene: C = color, c = albino u 2 nd gene: B = Brown, b = black

71. Gerbils

72. In Gerbils CcBb X CcBb Brown X Brown F1 = 9 brown (C_B_) 3 black (C_bb) 4 albino (cc__)

73. Result u Ratios often altered from the expected. u One trait may act as a recessive because it is “hidden” by the second trait.

74. Epistasis in Mice

75. Problem u Wife is type A u Husband is type AB u Child is type O Question - Is this possible? Comment - Wife’s boss is type O

76. Bombay Effect u Epistatic Gene on ABO group. u Alters the expected ABO outcome. u H = dominant, normal ABO u h = recessive, no A,B, reads as type O blood.

77. Genotypes u Wife: type A (I A I A, Hh) u Husband: type AB (I A I B, Hh) u Child: type O (I A I A, hh) Therefore, the child is the offspring of the wife and her husband (and not the boss).

78. Bombay - Detection u When ABO blood type inheritance patterns are altered from expected.

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80. Homework u Readings – Chapters 14, 47 u Lab – changed to Chi Square and other genetics. u Chapter 47 – Wed. 12/1 u Chapter 14 – Fri. 12/3

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82. Polygenic Inheritance u Factors that are expressed as continuous variation. u Lack clear boundaries between the phenotype classes. u Ex: skin color, height

83. Genetic Basis u Several genes govern the inheritance of the trait. u Ex: Skin color is likely controlled by at least 4 genes. Each dominant gives a darker skin.

85. Result u Mendelian ratios fail. u Traits tend to "run" in families. u Offspring often intermediate between the parental types. u Trait shows a “bell-curve” or continuous variation.

86. Genetic Studies in Humans u Often done by Pedigree charts. u Why? u Can’t do controlled breeding studies in humans. u Small number of offspring. u Long life span.

87. Pedigree Chart Symbols Male Female Person with trait

88. Sample Pedigree

89. Dominant Trait Recessive Trait

90. Human Recessive Disorders u Several thousand known: u Albinism u Sickle Cell Anemia u Tay-Sachs Disease u Cystic Fibrosis u PKU u Galactosemia

91. Sickle-cell Disease u Most common inherited disease among African-Americans. u Single amino acid substitution results in malformed hemoglobin. u Reduced O 2 carrying capacity. u Codominant inheritance.

93. Tay-Sachs u Eastern European Jews. u Brain cells unable to metabolize type of lipid, accumulation of causes brain damage. u Death in infancy or early childhood.

94. Cystic Fibrosis u Most common lethal genetic disease in the U.S. u Most frequent in Caucasian populations (1/20 a carrier).  Produces defective chloride channels in membranes.

95. Recessive Pattern u Usually rare. u Skips generations. u Occurrence increases with consaguineous matings. u Often an enzyme defect. u Affects males and females equally.

96. Human Dominant Disorders u Less common then recessives. u Affects males and females equally. u Ex: u Huntington’s disease u Achondroplasia u Familial Hypercholesterolemia

97. Inheritance Pattern u Each affected individual had one affected parent. u Doesn’t skip generations. u Homozygous cases show worse phenotype symptoms. u May have post-maturity onset of symptoms.

98. Genetic Screening u Risk assessment for an individual inheriting a trait. u Uses probability to calculate the risk.

99. General Formal R = F X M X D R = risk F = probability that the female carries the gene. M = probability that the male carries the gene. D = Disease risk under best conditions.

100. Example u Wife has an albino parent. u Husband has no albinism in his pedigree. u Risk for an albino child?

101. Risk Calculation u Wife = probability is 1.0 that she has the allele. u Husband = with no family record, probability is near 0. u Disease = this is a recessive trait, so risk is Aa X Aa =.25 u R = 1 X 0 X.25 u R = 0

102. Risk Calculation u Assume husband is a carrier, then the risk is: R = 1 X 1 X.25 R =.25 There is a.25 chance that every child will be albino.

103. Common Mistake u If risk is.25, then as long as we don’t have 4 kids, we won’t get any with the trait. u Risk is.25 for each child. It is not dependent on what happens to other children.

104. Carrier Recognition u Fetal Testing u Amniocentesis u Chorionic villi sampling u Newborn Screening

105. Fetal Testing u Biochemical Tests u Chromosome Analysis

106. Amniocentesis u Administered between 11 - 14 weeks. u Extract amnionic fluid = cells and fluid. u Biochemical tests and karyotype. u Requires culture time for cells.

108. Chorionic Villi Sampling u Administered between 8 - 10 weeks. u Extract tissue from chorion (placenta). u Slightly greater risk but no culture time required.

110. Newborn Screening u Blood tests for recessive conditions that can have the phenotypes treated to avoid damage. Genotypes are NOT changed. u Ex. PKU

111. Newborn Screening u Required by law in all states. u Tests 1- 6 conditions. u Required of “home” births too.

112. Multifactorial Diseases u Where Genetic and Environment Factors interact to cause the Disease.

113. Ex. Heart Disease u Genetic u Diet u Exercise u Bacterial Infection

114. Summary u Know the Mendelian crosses and their patterns. u Be able to work simple genetic problems (practice). u Watch genetic vocabulary. u Be able to read pedigree charts.

115. Summary u Be able to recognize and work with some of the “common” human trait examples.