Terminal Genetics lecture combineee.pptx

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1. LETHAL GENES By Dr. Afshan Afareen Lectures no. 15, 16

2. Genes which r esult in the r e duction of viability of an individual or become f o r de a t h o f i nd i viduals them are c all e d a s l e thal a c ause carrying genes. Cer t ain essential g en e s a r e a b solu t e l y f o r s u r v i v a l . Mu t a t ion in these genes creates lethal allele. LETHAL GENES Classical and Population Genetics 2

3. Lethal genes were first discovered by Lucien Cuénot while studying the inheritance of coat colour in mice. He expected a phenotype ratio from a cross of 3 yellow:1 white, but the observed ratio was 2:1. Classical and Population Genetics 3

4. The coat colour of mice is governed by a multiple allelic series in which A allele determines agouti, A Y allele determines yellow coat and a allele forms black coat. The dominance hierarchy is as follows: A Y > A > a The A Y allele acts as recessive lethal, since in the homozygous state (A Y A Y ), it kills the individual in early embryonic state. COAT COLOUR IN MICE Classical and Population Genetics 4

5. Thus, when two yellow coated heterozygotes (A Y A) are crossed, they produce a progeny showing a ratio of 2:1 since homozygous yellow individuals (A Y A Y ) are never born due to lethal effect of AY gene. Classical and Population Genetics 5

6. Lethal alleles fall into four categories. Early onset- lethal alleles which result in death of an organism at early stage of life, for example, during embryogenesis. Late onset- lethal allele which kills organism at their final stage of life are known as late onset allele. TYPES OF LETHAL ALLELES Classical and Population Genetics 6

7. 3. Conditional- lethal allele which kill an organism under certain environmental conditions only. e.g., some temperature sensitive alleles kill organisms only at high temperature. 4. Semi lethal – Lethal allele which kill only some individuals of the population but not all are know as semi lethal. Classical and Population Genetics 7

8. Scientists studying the fruit fly observed that pairwise combinations of some mutant alleles were not viable, whereas singly, the same mutant alleles did not cause death (Boone  et al ., 2007). In other words, some mutations are only lethal when paired with a second mutation. These genes are called synthetic lethal genes. When the functions of the two affected genes are not fully understood, scientists can create and study synthetic lethal mutants and their phenotypes to identify a gene's function. Mechanisms can also be hypothesized from the known functions of pairs of mutated alleles. Synthetic Lethal Genes Classical and Population Genetics 8

9. If both mutations occur in nonessential genes, a scientist could hypothesize that the two genes function in parallel pathways that share information with one another. Each of the two pathways could compensate for a defect in the other, but when both pathways have a mutation, the combination results in synthetic lethality. Synthetic lethality can also indicate that two affected genes have the same role, and therefore, lethality only results when both copies are nonfunctional and one gene cannot substitute for the other. Additionally, both genes may function in the same essential pathway, and the pathway's function may be diminished by each mutation. When an allele causes lethality, this is evidence that the gene must have a critical function in an organism. The discoveries of many lethal alleles have provided information on the functions of genes during development. Additionally, scientists can use conditional and synthetic lethal alleles to study the physiological functions and relationships of genes under specific conditions. Classical and Population Genetics 9

10. Lethal r ece s si v e . all e l e s a r e dom i na n t or Full y domina n t l e thal allele kills a n d o r g anism i n bot h hom o z y g ous heterozygous condition. Recessive lethal alleles kills organisms in homozygous condition only. Classical and Population Genetics 10

11. DOMINANT LETHAL GENES Dominant lethal allele kills both in homozygous and heterozygous states. Individuals with a dominant lethal allele die before they can leave progeny. Therefore, the mutant dominant lethal is removed from the population in the same generation in which it arose. Classical and Population Genetics 11

12. An example is the "creeper" allele in chickens, which causes the legs to be short and stunted. Creeper is a dominant gene, heterozygous chickens display the creeper phenotype. If two creeper chickens are crossed, one would expect to have (from Mendelian genetics) 3/4 of the offspring to be creeper and 1/4 to be normal. Instead the ratio obtained is 2/3 creeper and 1/3 normal. This occurs because homozygous creeper chickens die. EXAMPLES OF DOMINANT LETHAL ALLELES Classical and Population Genetics 12

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14. HUNTINGTON’S DISEASE Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. Classical and Population Genetics 14

15. Mutations in the HTT gene cause Huntington disease. The HTT gene provides instructions for making a protein called huntingtin. HH  Individual dies of Huntington’s disease Hh  Individual dies of Huntington’s disease hh  Normal individual Classical and Population Genetics 15

16. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Affected individuals may have trouble walking, speaking, and swallowing. Individuals with the adult-onset form of Huntington disease usually live about 15 to 20 years after signs and symptoms begin. Classical and Population Genetics 16

17. Classical and Population Genetics 17

18. Recessive lethal genes kill only when they are in homozygous state. They may be of two kinds: one which has no obvious phenotypic effect in heterozygotes. one which exhibits a distinctive phenotype when heterozygous. RECESSIVE LETHAL GENES Classical and Population Genetics 18

19. Brachydactyly – A genetic state in which the fingers are unusually short in heterozygotic condition. But, this condition is lethal during early years to homozygous recessive individuals due to major skeletal defects. Most surgeries for brachydactyly are cosmetic. Some therapy might be needed to help with kinesthetic activities. EXAMPLES OF RECESSIVE LETHAL ALLELLES Classical and Population Genetics 19

20. A mutation occurs in IHH gene which encodes proteins responsible for bone growth and differentiation. When a single mutated copy of the allele is present, the phenotype has just few deformations of skeletal bones. This is because one dose of functional IHH allele is almost enough to produce a required amount of a protein essential for a skeletal formation. If an organism inherits two mutated copies of IHH allele no protein essential for skeletal bones formation is produced and development of embryo cannot be continued - the embryo dies. What causes Brachydactyly? Classical and Population Genetics 20

21. Let's say that an allele a is recessive and codes for a completely dysfunctional form of a protein essential for bone growth, and A is a dominant wild type allele. If heterozygotes for these alleles procreate, then: Classical and Population Genetics 21

22. A genetic state that is often fatal in the homozygous recessive condition. People who inherit one good copy of the gene and one mutated copy are carriers. They are clinically normal, but can still pass the defective gene to their children. When sickle-shaped red blood cells get stuck in blood vessels, patients can have episodes of pain called crises. Other symptoms include delayed growth, strokes, and jaundice (yellowish skin and eyes because of liver damage). Sickle Cell Anemia – Classical and Population Genetics 23

23. Genetics of Sickle Cell Anemia Genotypes Phenotypes Hb N Hb N Normal haemoglobin Hb N Hb S Sickle cell trait Hb S Hb S Sickle cell anaemia Animation showing sickle cells

24. A genetic state that is fatal to every homozygous recessive person by age 30. Sticky mucus accumulates in the lungs giving rise to constant and risky respiratory infections. It is caused due to malfunctioning of chloride ion channels in ducts. Cystic Fibrosis Classical and Population Genetics 27

25. Lungs in cystic fibrosis Normal lung CF lung Dilated crypts filled with mucus and bacteria. Normal alveolar appearance

26. Children with this disease are born with crusted leathery skin with deep splits. These splits lead to bleeding, infection and death. In Ichthyosis, the skin's natural shedding process is slowed or inhibited and in some types, skin cells are produced too rapidly. Most types of autosomal recessive congenital ichthyosis require two forms of treatment - a reduction in the amount of scale buildup and moisturising of the underlying skin. Congenital Ichthyosis Classical and Population Genetics 29

27. Probability and Genetics By Dr. Afshan Afareen Lectures no. 17, 18

28. -Mendel used the principles of probability to explain the results of his genetic crosses. A. Genetics and Probability Probability – the likelihood that a particular event will occur, ex : coins – have a 50/50 shot of heads or tails. Problem : Determine the probability of flipping heads on a coin 3 times in a row. ½ x ½ x ½ = 1/8 *Past outcomes DON’T affect future outcomes. -Segregation of alleles is completely random like coin tossing. -The principles of probability can be used to predict the outcomes of genetic crosses. Classical and Population Genetics 32 II. Probability and Punnett Squares

29. B. Punnett Squares *Gene combinations that might result from a genetic cross can be determined by using a Punnett square. Punnett square – a diagram showing the gene combinations that might result from a genetic cross. Classical and Population Genetics 33 II. Probability and Punnett Squares

30. 1 . Types of gametes produced by P or F1 generations are shown along the top & left sides of the square. 2. Possible gene combinations for the F1 or F2 offspring appear in the 4 boxes that make up the square. Classical and Population Genetics 34 In a Punnett square the

31. -Organisms with 2 identical alleles for a trait (TT or tt ) are called homozygous , homo = same. -Organisms with 2 different alleles for the same trait (Tt) are called heterozygous , hetero = different. -Homozygous organisms are true-breeding or pure for a trait & heterozygous organisms are hybrid for a trait. Classical and Population Genetics 35 Homozygous vs. Heterozygous

32. What are the genotypic & phenotypic ratios of the F1 generation of plants in this picture (assuming A = yellow seeds/a = green seeds)? Genotypic = 1 AA : 2 Aa : 1 aa Phenotypic = 3 yellow seeds : 1 green seed Classical and Population Genetics 36 Genotype vs. Phenotype

33. *Probabilities predict the average outcome of a large # of events. -Probability CAN’T predict the precise outcome of an individual event, ex : flipping a coin 2x & getting heads twice as opposed to heads once & tails once. The same is true of genetics & the probability of expected ratios in a population. -In order to get close to expected values, one must flip a coin many times/in genetics produce many offspring. Classical and Population Genetics 37 C. Probabilities Predict Averages

34. Mendel ’ s laws of segregation and independent assortment reflect the same laws of probability that apply to tossing coins or rolling dice. The probability scale ranged from zero (an event with no chance of occurring) to one (an event that is certain to occur). Classical and Population Genetics 38 Mendelian inheritance reflects rule of probability…

35. The probability of tossing heads with a normal coin is 1/2. AND The probability of tossing tails with a normal coin is 1/2. Classical and Population Genetics 39 Tossing a coin

36. The probability of rolling a 3 with a six-sided die is 1/6 And The probability of rolling any other number is 1 - 1/6 = 5/6 . Classical and Population Genetics 40 Rolling a Dice

37. When tossing a coin, the outcome of one toss has no impact on the outcome of the next toss. Each toss is an independent event, just like the distribution of alleles into gametes. Like a coin toss, each ovum from a heterozygous parent has a 1/2 chance of carrying the dominant allele and a 1/2 chance of carrying the recessive allele. The same odds apply to the sperm. Classical and Population Genetics 41

38. When to use it: When you want to determine the probability that two or more independent events will occur together in some specific combination . How to use it: Compute the probability of each independent event. Then, multiply the individual probabilities to obtain the overall probability of these events occurring together. Classical and Population Genetics 42 Rule of Multiplication

39. The probability that two coins tossed at the same time will land heads up is 1/2 x 1/2 = 1/4. Similarly, the probability that a heterozygous pea plant (Pp) will produce a white-flowered offspring (pp) depends on an ovum with a white allele mating with a sperm with a white allele. This probability is 1/2 x 1/2 = 1/4. Classical and Population Genetics 43 EXAMPLE:

40. The rule of multiplication also applies to dihybrid crosses . For a heterozygous parent ( YyRr ) the probability of producing a YR gamete is 1/2 x 1/2 = 1/4 . We can use this to predict the probability of a particular F 2 genotype without constructing a 16-part Punnett square. The probability that an F 2 plant will have a YYRR genotype from a heterozygous parent is 1/16 ( 1/4 chance for a YR ovum and 1/4 chance for a YR sperm ). Classical and Population Genetics 44 C. Probabilities Predict Averages

41. The rule of addition also applies to genetic problems. Under the rule of addition, the probability of an event that can occur two or more different ways is the sum of the separate probabilities of those ways. Classical and Population Genetics 45 Rule of Addition

42. For example, there are two ways that F 1 gametes can combine to form a heterozygote. The dominant allele could come from the sperm and the recessive from the ovum (probability = 1/4). Or, the dominant allele could come from the ovum and the recessive from the sperm (probability = 1/4). The probability of a heterozygote is 1/4 + 1/4 = 1/2. Classical and Population Genetics 46 C. Probabilities Predict Averages

43. SEX LINKED TRAITS By Dr. Afshan Afareen Lectures no. 17, 18

44. Sex-Linked Inheritance Classical and Population Genetics 48 Sex linked inheritance varies the Mendel number of 3:1 by having males a 50/50 percent chance of inheriting the characteristic on the X chromosome only. Remember, Females have XX and Males are XY . The Y carries little genetic information, mainly those that contribute to male characteristics. (About 87 genes total.) The X carries a lot more genetic information. (About 2000!) Comparison of the X and Y sex (23 rd pair) chromosomes

45. Inheritance Classical and Population Genetics 49 For a number of traits, gene expression differs in males and females The causes fall under 3 categories: Sex-Linked Sex-Limited Sex-Influenced

46. SEX Linked Classical and Population Genetics 50 A major extension of the Mendelian principles is the pattern of inheritance exhibited by sex-linked characteristics, characteristics determined by genes located on the sex chromosomes. Genes on the X chromosome determine X-linked . characteristics; those on the Y chromosome determine Y-linked characteristics. Because the Y chromosome of many organisms contains little genetic information, most sex-linked characteristics are X linked. Males and females differ in their sex chromosomes; so the pattern of inheritance for sex-linked characteristics differs from that exhibited by genes located on autosomal chromosomes. It has been observed that the genes occurring only in the X chromosomes are represented twice in female (because female contains 2X chromosomes) and once in male (because male has only one X chromosome).

47. Sex Linked Traits Classical and Population Genetics 51 The genes which occur exclusively on the X chromosome (mammals, Drosophila, etc.) or on the analogous Z chromosome (in birds and other species with ZO or ZW mechanism of sex determination) are called X- or Z -linked genes . The genes which exclusively occur in Y chromosome are called holandric genes . The inheritance of X- or Z-linked and holandric genes is called sex-linked inheritance.

48. Sex-Linked Traits Classical and Population Genetics 52 In poultry, the male has the genotype XX, while the female has the genotype Xw . An example of a sex-linked trait in poultry is the barring of Barred Plymouth Rock chickens. If barred hens are mated to non-barred males, all of the barred chicks from this cross are males, and the non-barred chicks are females.

49. TYPES Classical and Population Genetics 53 In XX– XY type organisms, sex-linked genes can be classified into following three types: a. X-linked. The X-linked type sex-linked inheritance is performed by those genes which are localized in the nonhomologous sections of X-chromosome, and that have no corresponding allele in Y chromosome. The X-linked genes are commonly known as sex-linked genes. b. Y-linked . The Y-linked type sex-linked inheritance is performed by those genes which are localized in the non-homologous section of Y chromosome, and that have no alleles in X-chromosome. The Y-linked genes are commonly known as holandric genes (Greek, holos = whole, and andros = man). c. XY-linked . The XY linked type sex-linked inheritance is performed by those genes which are localized in homologous sections of X and Y chromosomes.

50. Characteristics of Sex-linked Inheritance Classical and Population Genetics 54 The characteristics for sex linked inheritance are as follows: a. The pattern of inheritance of sex linked trait is criss-cross . The father passes the X linked allele of a trait to the daughters who pass it on to the grandsons. The father cannot pass a sex linked allele to a son directly. b. The mother can pass the allele of a trait to both daughter and son. c. Only homozygous females can express a recessive trait, while heterozygous female are carriers and do not express the trait. d. Males express the trait immediately because of the absence of a corresponding allele. This is the reason why males suffer from sex linked disorders more than females. e. Most of the sex linked traits are recessive. Some examples of sex linked traits include Haemophilia or Bleeder’s disease, Daltinism or Colour blindness

51. Sex-Linked Disorders Classical and Population Genetics 55 The vast majority of affected individuals are male . Affected males never pass the disease to their sons because there is no male-to-male transmission of the X chromosome. Affected males pass the defective X chromosome to all of their daughters , who are described as carriers . This means they carry the disease-causing allele but generally show no disease symptoms since a functional copy of the gene is present on the other chromosome. Female carriers pass the defective X chromosome to… half their sons (who are affected by the disease) half their daughters (who are therefore also carriers). The other children inherit the normal copy of the chromosome. The overall pattern of the disease is therefore characterized by the transmission of the disease from affected males to male grandchildren through carrier daughters , a pattern sometimes described as a ' knight's move '. Affected females, with two deficient X chromosomes, are the rare products of a marriage between an affected male and a carrier (or affected) female.

52. Who is affected by Sex-Linked Disorders? Classical and Population Genetics 56 Genes for certain traits are on the X chromosome only… Since Men only receive one X chromosome then they are more likely to inherit these types of disorders. Who gives men the X Chromosome? Women are somewhat protected since they receive two X chromosomes and are less likely to inherit these types of disorders. What do you think happens when they get only one defective copy of an X chromosome?

53. How do you solve Sex-linked Problems? Classical and Population Genetics 57 You determine which trait (or disorder) is dominant or recessive . Set up a punnett square using XX for females and XY for males . Assign alleles for X only ! Solve as usual, keeping in mind that the Y chromosome has no allele ! Genotypes : X R X r , X R Y Phenotypes : All offspring have red eyes. If Red eyes are dominant and sex-linked, show the cross between a homozygous red eyed female and a white eyed male.

54. 2- Dominant X-linked Traits Classical and Population Genetics 58 Dominant X- Likned genes can be detected in human pedigrees (also in Drosophila) through the following clues : (a) It is more frequently found in the female than in the male of the species. (b) The affected males pass the condition on to all of their daughters but to none of their sons (c) Females usually pass the condition (defective phenotype) on to one-half of their sons and daughters (d) A X-linked dominant gene fails to be transmitted to any son from a mother which did not exhibit the trait itself. In humans, X-linked dominant conditions are relatively rare. One example is hypophosphatemia(vitamin D-resistant rickets). Another example includes hereditary enamel hypoplasia (hypoplastic amelogenesis imperfecta), in which tooth enamel is abnormally thin so that teeth appear small and wear rapidly down to the gums.

55. X-Linked Dominant Classical and Population Genetics 59

56. X-linked recessive Classical and Population Genetics 60 ( i ) The X-linked recessive phenotype is usually found more frequently in the male than in the female. This is because an affected female can result only when both mother and father bear the X-linked recessive allele (e.g., XA Xa × XaY ), whereas an affected male can result when only the mother carries the gene. Further, if the recessive X-linked gene is very rare, almost all observed cases will occur in males. (ii) Usually none of the offspring of an affected male will be affected, but all his daughters will carry the gene in masked heterozygous condition, so one half of their sons (i.e., grandsons of F1 father) will be affected (iii) None of the sons of an affected male will inherit the X-linked recessive gene, so not only will they be free of the defective phenotype; but they will not pass the gene along to their offspring

57. Classical and Population Genetics 61

58. X-Linked recessive Classical and Population Genetics 62 Fig. Pedigree showing how X-linked recessive genes are expressed in males, then carried unexpressed by females in the next generation, to be expressed in their sons. II.3 and III.4 heterozygous or carrier females are not distinguished phenotypically

59. X-Linked Recessive Genes Classical and Population Genetics 63 Example of Inheritance of X-Linked Recessive Genes The crisscross inheritance of recessive X- linked genes can be well understood by following classical examples in Drosophila, man, moth and chikens etc.: 1. Inheritance of X-Linked Gene for Eye Colour in Drosophila In Drosophila, the gene for white eye colour is X linked and recessive to another X-linked, dominant gene for red-eye colour . It is discovered by Morgan in 1910. Following crosses between white eyed and red eyed Drosophila will make clear the characteristic criss-cross inheritance of gene for white eyed color in it :

60. X-Linked Recessive Genes Classical and Population Genetics 64 (a) Red eyed female × White eyed male If a wild red eyed female Drosophila is crossed with a mutant white eyed male Drosophila, all the F1 individuals irrespective of their sex have red eyes P X R X R X X r Y F1 X R X r , X R Y Red eyed female , Red eyed male •When the red eyed male and red eyed female individuals of F1 are intercrossed, X R X r X X R Y X R X R , X R Y , X R X r , X r Y Red eyed female, red eyed male, Red eyed female, white eyed male 3 red : 1white eyed •the F2 progeny is found to include an exclusively red eyed female population and a male population with 50 per cent red eyed individuals and 50 per cent white eyed individuals. Thus, F2 generation includes red eyed and white eyed individuals in the ratio of 3: 1.

61. X-Linked Recessive Genes Classical and Population Genetics 65 b) White eyed female × Red eyed male. When a white eyed female Drosophila is crossed with a red eyed male Drosophila, all the female individuals in the F1 generation are red eyed X r X r x X R Y X R X r , X r Y Red eyed female , white eyed male •When these red eyed female individuals and white eyed male individuals of F1 are intercrossed, X R X r x X r Y X R X r , X R Y, X r X r , X r Y Red eyed female , Red eyed male , white eyed female , white eyed male •the female population of F2 generation is found to include 50 per cent red eyed and 50 per cent white eyed flies. Similarly, the male population of F2 includes 50 per cent, red eyed and 50 per cent white eyed flies. • The results of these experiments, thus, are clearly indicating that the trait located on a sex chromosome alternates the sex from one generation to the next generation, i.e , the trait of white eyes transfers from P1 father to F1 daughter and from F1 daughter to F2 son.

62. 2 . Inheritance of X-Linked Recessive Genes in Humans Classical and Population Genetics 66 In human beings more than 150 confirmed or highly probable X-linked traits are known; most of these are recessives. Certain well known examples of X-linked recessive genes in humans are (1)red- green colour blindness or daltonism , (2) haemophilia . (3) night blindness; (4) white frontal patch of hair.

63. Colour blindness Classical and Population Genetics 67 (1). In human beings, a dominant X- linked gene is necessary for the formation of the colour sensitive cells, the cones, in the retina of eye. According to trichromatic theory of colour vision, there are three different types of cones, each with its characteristic pigment that react most strongly to red, green and violet light. The recessive form of this gene (i.e., presence of recessive X-linked allele for colour blindness) is incapable of producing the colour sensitive cones and the homozygous recessive females ( X c X c ) and hemizygous recessive males ( X c Y) are unable to distinguish between these two colours . •The frequency of colour blind women is much less than colour blind man? ( i ) Marriage between colour -blind man and normal visioned woman. When colour -blind man marries with a normal visioned woman, then they will produce normal visioned male and female individuals in F1. The marriage between a F1 normal visioned woman and normal visioned male will produce in F2 two normal visioned female, one normal visioned male and one colour -blind male

64. Colour blindness Classical and Population Genetics 68 Normal female Colour -blind male Parent : X + X + X X c Y Gametes : (X + ) ( X c ) (Y) F1: ½ X + X c : ½ X + Y (Marriage between a carrier female and a normal male produces the carrier female x Normal male P2 X + X c X + Y G2 X + , X C X + , Y F2 X + X + , X + Y, X + X C , X C Y Normal female Normal male carrier female Colour -blind male

65. Haemophilia Classical and Population Genetics 69 . Haemophilia is the most serious and notorious disease which is more common in men than women. This is also known as bleeder’s disease. The person which contains the recessive gene for haemophillia lacks in normal clotting substance (thromboplastin) in blood so minor injuries cause continuous bleeding and ultimate death of the person due to haemorrhages . This hereditary disease was reported by John Cotto in 1803 in man. (a) Haemophilia A. It is characterized by lack of antihaemophilic globulin (Factor VIII). About four fifths of the cases of haemophilic are of this type. (b) Haemophilia B. It is also called“christmas disease” after the family in which it was first described in detail. Haemophilia B results from a defect in plasma thromboplastic component (factor IX). This is milder form of haemophilia . Parents : X + X h × X + Y Normal mother(carrier) Normal father Gametes: (X + ) ( X h ) (X + ) (Y) Progeny : X + X + , X + X h , X + Y , X h Y Normal daughter, Normal (carrier), Normal , Hemophilic

66. B. INHERITANCE OF Y-LINKED GENES Classical and Population Genetics 70 Genes in the non-homologous region of the Y chromosome pass directly from male to male. In man, the Y-linked or holandric genes are transmitted directly from father to son Having hairy ears was once thought to be a Y-linked trait in humans, but that hypothesis has been discredited. It has often been said that little is known about genes that may be Y-linked. This is no longer true. As of the year 2012, about three dozen genes were known to be Y-linked including: ASMTY (which stands for acetyl serotonin methyltransferase), TSPY (testis-specific protein) • Y-Chromosome deletions are a frequent genetic cause of male infertility. In some males a small deletion in the DAZ gene ( deleted in azoosprmia ) on the Y chromosome cause azoospermia

67. Sex Linked Traits Classical and Population Genetics 71

68. Sex- Influence Inheritance Classical and Population Genetics 72 Modes of gene expression differ between males and females An allele may be expressed as a dominant in one sex and a recessive in the other Scurs on cattle is a sex-influenced inheritance The allele for scurs is dominant in males and recessive in females A male with one copy will be scurred, but a female must have 2 copies

69. SEX-INFLUENCED GENES Classical and Population Genetics 73 • Sex influenced genes are those whose dominance is influenced by the sex of the bearer. Thus, male and female individuals may be similar for a particular trait but give different phenotypic expressions of the same trait. Example : 1- In man the baldness may occur due to disease, radiation or thyroid defects but in some families balldness is found to be inherited trait. In such inherited baldness the hairs gradually become thin on head top, leaving ultimately a fringe of hair low on the head and commonly known as pattern baldness. The gene B for baldness is found to be dominant in males and recessive in females. In heterozygous condition it expresses itself only in the presence of male hormones (in male sex): Genotype Phenotypes Men women BB Bald Bald Bb Bald Non-bald bb Non-bald Non-bald 2- In sheep, the genes for the development of horns is dominant in males and recessive in female.

70. SEX-LIMITED GENES Classical and Population Genetics 74 Sex-limited genes are autosomal genes whose phenotypic expression is determined by the presence or absence of one of the sex hormones. Their phenotypic effect is limited to one sex or other. In other words, the penetrance of a sex-limited gene in one sex remain zero. Sex-limited genes are responsible for sexual dimorphism, which is a phenotypic (directly observable) difference between males and females of the same species. These differences can be reflected in size, color, behavior Example 1. The bulls have genes for milk production which they transmit to their daughters, but they or their sons are unable to express this trait. The production of milk is, therefore, limited to variable expression only in the female sex. 2. Beard development in human beings is a sex limited trait as men normally have beards, whereas women normally do not. Likewise, the genes for male voice, body hair and physique are autosomal in human beings, but they are expressed only in the presence of androgens which are absent in females. 3. In chicken the recessive gene (h) for cock feathering is male sex-limited (i.e., it is penetrant only in male environment)

71. Practice: Your Turn! Classical and Population Genetics 75 Hemophilia is a sex-linked trait where X H gives normal blood clotting and is dominant to the hemophilia allele X h . Identify the genotypes of… 1) a woman with normal blood clotting whose father had hemophilia 2) a normal man whose father had hemophilia. What is the probability that a mating between these two individuals will produce a child, regardless of sex, that has hemophilia?

72. Check your work Classical and Population Genetics 76 1) the woman has normal clotting so she has one X H but she got a X h from her father, so she is X H X h 2) the man is X H Y since he got the Y from his father and he is normal so must be X H Y X H X h X H X H X H X H X h Y X H Y X h Y Genotypes : ¼ X H X H Phenotypes: ½ unaffected girls ¼ X H X h ¼ unaffected boy ¼ X H Y ¼ affected boy ¼ X h Y Notice how girls are “protected” from disorders and carry them.

73. Pedigree By Dr. Afshan Afareen Lectures no. 1 9 , 20

74. P edigree Classical and Population Genetics 78 What is a  pedigree? •A graphic representation of how a trait is passed from parents to offspring. •A chart of the genetic history of family over several generations. •A genetic counselor would find out about your family history and make this chart to analyze.

75. Introduction of Pedigree Analysis Classical and Population Genetics 79 •A genetic counselor would find out about your family history and make this chart to analyze A v ery important tool for studying human inherited diseases. These diagrams make it easier to visualize relationships within families, particularly large extended families. Pedigrees are often used to determine the mode of inheritance (dominant, recessive, etc.) of genetic diseases.   Why do Pedigrees?   Punnett squares and chi-square tests work well for organisms that have large numbers of offspring and controlled matings, but humans are quite different: 1.small families. Even large human families have 20 or fewer children. 2. Uncontrolled matings, often with heterozygotes. 3. Failure to truthfully identify parentage.

76. Introduction of Pedigree Analysis Classical and Population Genetics 80 Individuals may  wish to be tested if: A.)There is a family history of one specific disease. B.)They show symptoms of a genetic disorder, C.)They are concerned about passing on a genetic problem to their children.

77. Introduction of Pedigree Analysis Classical and Population Genetics 81

78. Categories of Inheritance Classical and Population Genetics 82 Autosomal means  inherited on chromosome 1-22 while sex- linked means inherited on either X orY chromosome. Autosomal recessive e.g., PKU,Tay -Sachs, albinism Autosomal dominant e.g., Huntington’s Disease X-linked recessive (meaning this allele is found on only the X chromosome: can be in males or females) e.g., color-blindness, hemophilia X-linked dominant (meaning this allele is found on X chromosomes; can be in males or females) e.g., hypophosphatemia Y-linked (meaning the allele is found on theY chromosome and can only be in males.

79. Autosomal Recessive Pedigree Classical and Population Genetics 83 Trait is  rare in the pedigree • Trait often skips generations (hidden in heterozygous carriers) • Trait affects males and females equally • Possible diseases include: Cystic fibrosis, Sickle cell anemia, Phenylketonuria (PKU), Tay-Sachs disease

80. Autosomal dominant Pedigree Classical and Population Genetics 84 Trait is  common in the pedigree Trait is found in every generation Affected individual also transmit the trait to about 1/2 of their children (regardless of sex). There are few autosomal dominant human diseases but some rare traits have this inheritance pattern. For example: achondroplasia (a sketelal disorder causing dwarfism)

81. Huntington’s Disease (Autosomal dominant) Classical and Population Genetics 85 Half the people  in the Venezuelan village of Barranquitas are affected - A large-scale pedigree analysis was conducted including 10,000 people - Example for one

82. X–linked Ressive Pedigree Classical and Population Genetics 86 • Trait is  rare in pedigree • Trait skips generations • Affected fathers DO NOT pass to their sons • Males are more often affected than females • Females are carriers (passed from mom to son)

83. X-linked Dominant Pedigrees Classical and Population Genetics 87 • Trait is  common in pedigree • Affected fathers pass to ALL of their daughters • Males and females are equally likely to be affected • X-linked dominant diseases are extremely unusual • Often, they are lethal (before birth) in males and only seen in females ex. incontinentia pigmenti (skin lesions) ex. X-linked rickets (bone lesions)

84. Y-linked Inheritance Classical and Population Genetics 88 Traits on  the Y chromosome are only found in males, never in females. The father’s traits are passed to all sons. Dominance is irrelevant: there is only 1 copy of each Y-linked gene (hemizygous).

85. Large Pedigrees Classical and Population Genetics 89 We are  now going to look at detailed analysis of dominant and recessive pedigrees. To simplify things, we are going to only use these two types. The main problems: 1. determining inheritance type 2. determining genotypes for various individuals 3. determining the probability of an affected offspring between two members of the chart.

86. Dominant vs Recessive Classical and Population Genetics 90   1. If two  affected people have an unaffected child, it must be a dominant pedigree: D is the dominant mutant allele and d is the recessive wild type allele. Both parents are Dd and the normal child is dd. 2. If two unaffected people have an affected child, it is a recessive pedigree: R is the dominant wild type allele and r is the recessive mutant allele. Both parents are Rr and the affected child is rr . 3. If every affected person has an affected parent it is a dominant pedigree.

87. Assigning Genotypes for Dominant Pedigrees Classical and Population Genetics 91 1 . Affected children of an affected parent and an unaffected parent must be heterozygous Dd, because they inherited a d allele from the unaffected parent. 2 . The affected parents of an unaffected child must be heterozygotes Dd, since they both passed a d allele to their child. 3 . Outsider rule for dominant autosomal pedigrees: An affected outsider (a person with no known parents) is assumed to be heterozygous (Dd). 4 . If both parents are heterozygous Dd x Dd, their affected offspring have a 2/3 chance of being Dd and a 1/3 chance of being DD.

88. Assigning Genotypes for Recessive Pedigrees Classical and Population Genetics 92 1. all  affected are rr . 2. If an affected person ( rr ) mates with an unaffected person, any unaffected offspring must be Rr heterozygotes, because they got a r allele from their affected parent. 3. If two unaffected mate and have an affected child, both parents must be Rr heterozygotes. 4. Recessive outsider rule: outsiders are those whose parents are unknown. In a recessive autosomal pedigree, unaffected outsiders are assumed to be RR, homozygous normal. 5. Children of RR x Rr have a 1/2 chance of being RR and a 1/2 chance of being Rr. Note that any siblings who have an rr child must be Rr. 6. Unaffected children of Rr x Rr have a 2/3 chance of being Rr and a 1/3 chance of being RR.

89. Conditional Probability Classical and Population Genetics 93 Determining the  probability of an affected offspring for most crosses is quite simple: just determine the parents’ genotypes and follow Mendelian rules to determine the frequency of the mutant phenotype. In some cases, one or both parents have a genotype that is not completely determined. For instance, one parent has a 1/2 chance of being DD and a 1/2 of being Dd. If the other parent is dd and this is a dominant autosomal pedigree, here is how to determine the overall probability of an affected phenotype: 1. determine the probability of an affected offspring for each possible set of parental genotypes. 2. Combine them using the AND and OR rules of probability

90. Conditional Probability Classical and Population Genetics 94 In our  example, one parent has a 1/2 chance of being Dd and a 1/2 chance of being DD, and the other parent is dd. There are thus 2 possibilities for the cross: it could be DD x dd, or it could be Dd x dd. We have no way of knowing for sure. If the cross is DD x dd, all the offspring as Dd, and since the trait is dominant, all are affected. On the other hand, if the cross is Dd x dd, ½ the offspring are Dd (affected) and ½ are dd (normal). So, there is a ½ chance that the mating is DD x dd, with all offspring affected, and a ½ chance that the mating is Dd x dd, with ½ the offspring affected. Or: (1/2 * 1) + (1/2 * 1/2) = overall probability = 1/2 + 1/4 =3/4 20

91. Pedigrees in Real life Classical and Population Genetics 95 Remember: • D ominant traits  may be rare in a population • recessive traits may be common in a population • alleles may come into the pedigree from 2 sources • mutation happens • often traits are more complex • affected by environment & other genes

92. Queen Victoria Descendants and Hemophilia Classical and Population Genetics 96

93. Home Work Classical and Population Genetics 97 Find out which  family members (as many as you can; siblings, parents, grandparents, aunts, uncles, cousins, great-grand parents, etc.) with listed traits.

94. Problems Classical and Population Genetics 98   Problems 3. How many children does  this family have? ______ What are the sexes of the children? ______ Fill out the blanks of the pedigree below (AA, Aa, aa) How many children does  this family have? 4.What are the sexes of the children? Female, Male How many  children does the original couple have? ______ . How many grandchildren? ________ What are the sexes of the children? ___________

95. Population Genetics By Dr. Afshan Afareen Lectures no. 21 , 22, 23

96. Population genetics Classical and Population Genetics 100 Population genetics : is the genetics of a population dealing principally with gene and genotype frequencies through time and space . Population genetics  is the study of change in the frequencies of allele and genotype within a population. Population geneticists study the genetic structure of populations, and how they change geographically and over time. Population is a collection of individuals or data. It may be static or dynamic. A static population is one that existed at a particular time only. A dynamic population is one that existed over time and is maintained from generation to generation through procreation of new individuals, i.e. progeny.

97. Population genetics Classical and Population Genetics 101 i ) Gene frequency A character in an individual that passes on from generation to generation due to breeding of the parents is controlled by genes. The distribution of genes in different individual of the population is one of the properties of a population and is expressed as ‘ Gene frequency ’.

98. ESTIMATION OF ALLELE FREQUENCIES Classical and Population Genetics 102  

99. DERIVATIVES OF LAW Classical and Population Genetics 103 A large population that is not in equilibrium attains equilibrium after one generation of random mating, provided mutation, migration and selection are absent. The genotype frequency of the progeny is fully determined by the gene frequency of the parents in an equilibrium population and the gene frequency is obtained by taking square-root of the homozygote frequency. The frequency of the heterozygotes in an equilibrium population is never more than 50 per cent.

100.   Hardy Weinberg Principle Classical and Population Genetics 104 Hardy  Weinberg principle States that ; Under the certain condition, allelice frequences, remains constants from generation to generation. If any one condition is not made, genetic equilibrium will be disturbed and the population may be evolved. ( p+q )² p² + 2pq + q² =1

101. Aa aa AA aa aa Aa Aa Aa AA AA AA AA AA AA AA = 8/15 (53%) Aa = 4/15 (27%) aa = 3/15 (20%) AA A population: Phenotype frequencies 1/3 red and 2/3 green Total number = 15, frequency of Classical and Population Genetics 105

102. Aa aa AA Total number of alleles in the gene pool = 2 x # individuals Individuals have 2 alleles for each gene Classical and Population Genetics 106

103. Aa aa AA aa aa Aa Aa Aa AA AA AA AA AA AA A population has a frequency of alleles Total number of alleles = 30, frequency of A = 20/30 (67%) a = 10/30 (33%) Classical and Population Genetics 107

104. aa aa aa A population fixed for the “a” allele aa aa aa aa aa aa aa aa aa aa aa A population fixed for the “a” allele Classical and Population Genetics 108

105. Aa aa AA aa aa Aa Aa Aa AA AA AA AA AA AA A population with genetic variation A population: Phenotype frequencies 1/3 red and 2/3 green Total number = 15, frequency of Classical and Population Genetics 109

106. 64 32 4 x 2 x 2 RR Rr rr 128 R Plants in population Alleles in the gene pool 32 R 32 r 8 r 160 R alleles 40 r alleles RR Rr rr Classical and Population Genetics 110

107. 64 32 4 x 2 x 2 RR Rr rr 128 R Plants in population Alleles in the Gene pool 32 R 32 r 8 r 160 R alleles 40 r alleles 160 / 200 = .8 = p 40 / 200 = .2 = q Classical and Population Genetics 111 RR Rr rr

108. Probability of observing event 1 AND event 2 = the product of their probabilities. P[2 R alleles from 2 gametes]? Probability of each R = .8 Probability of RR = .8 x .8 = .64 = p x p = p 2 160 / 200 = .8 = p 40 / 200 = .2 = q What is the probability of an offspring with the genotype RR In the next generation? Classical and Population Genetics 112

109. Probability of observing event 1 AND event 2 = the product of their probabilities. Pr : 2 r alleles from 2 gametes? Probability of each r = .2 Probability of rr = .2 x .2 = .04 = q x q = q 2 160 / 200 = .8 = p 40 / 200 = .2 = q What is the probability of an offspring with the genotype rr In the next generation? Classical and Population Genetics 113

110. Pr : one r and one R from 2 gametes? P[ r and R] or P[R and r] = (.2 x .8) + (.8 x .2) = .32 = (p x q) + (p x q) = 2pq 160 / 200 = .8 = p 40 / 200 = .2 = q What is the probability of an offspring with the genotype Rr In the next generation? Classical and Population Genetics 114

111. p 2 + 2pq + q 2 = 1 Frequency of RR Frequency of Rr Frequency of rr Classical and Population Genetics 115

112. Classical and Population Genetics 116

113. Genetic Variations Classical and Population Genetics 117 Genetic Variation in  Natural Populations Types  of Variation Phenotypic variation: it’s a genetical basis morphological variation its some tie continuous and some time discontinuous. e.g salmonberry and Two-spotted ladybird beetle the  variance that is due to variation among individuals in the alleles that they have, excludes environmentally-caused variation

114. Fossils - preserved evidence of previously living things Classical and Population Genetics 118

115. Homology - similarity caused by common ancestry Classical and Population Genetics 119

116. Early embryos of diverse groups share many features. As development proceeds, embryonic forms diverge and become more similar to adults of their own species (von Baer’s law) Homology in early embryonic form Classical and Population Genetics 120

117. Why Allele Frequencies Change Classical and Population Genetics 121   Why Allele Frequencies  Change • Five evolutionary forces can significantly alter the allele frequencies of a population Mutation Migration Genetic drift 4. Nonrandom mating 5. Selection  

118. Mutation Classical and Population Genetics 122     • Errors in  DNA replication The ultimate source of new variation Mutation It is a rare event in nature. It can occur in both the directions, i.e. forward and backward. If it is recurrent, it can change the gene and genotype frequency of the population. If mutation occurs continuously in a gene it is called recurrent mutation. Some mutations increase fitness or lead to the evolution of new species by creating new or improved phenotypes. Some mutations lower fitness. Many mutant alleles produce phenotypes that are so abnormal that they either cause death or reduce viability severely. Other cause only small reductions in viability.

119. Original population is fixed for the green allele Mutation Mutation creates new alleles Mutation Classical and Population Genetics 123

120. Original population is fixed for the green allele Mutation Mutation creates new alleles But recall that mutations are rare – about 1 in 100,000 per generation, and some of those mutations are lethal or deleterious Mutation Classical and Population Genetics 124

121. Gene flow – movement between populations can change their allele frequencies Population 1 Population 2 Mutation Classical and Population Genetics 125

122. Gene flow - exchange of alleles among population changes gene frequencies Population 1 Population 2 Before : p = .33 q=.67 p = .67 q=.33 After: p = .37 q=.63 p = .63 q=.37

123. Migration Classical and Population Genetics 127   Movement of individuals  from one population to another – Immigration: movement into a population – Emigration: movement out of a population A very potent agent of change The change in gene frequency due to migration depends on the preparation of individuals that enter into the population and their gene frequency. The change in gene frequency due to migration q = m ( q m -q) q- initial gene frequency of the population q m - gene frequency in the immigrants and ‘m’ is the proportion of immigrants entering into the population

124. SMALL POPULATIONS Classical and Population Genetics 128 In a large population the gene frequencies are inherently stable in the absence of mutation, migration and selection. The gametes that transmit genes to the next generation carry a sample of genes in the parent generation and, if the sample is not large, the frequencies are liable to change can be predicted, the direction of change cannot be predicted. This results in dispersion of gene frequencies and is called the dispersive process (random genetic drift).

125.     Effects of chance  in small populations - genetic drift The smaller the population, the less genetic variety it has. ▪ In a very small population, alleles can be lost from one generation to the next, simply by random chance. ▪ When a population evolves only because of this type of random sampling error, GENEC DRIFT is taking place. ▪ The smaller the sample, the greater the chance of deviation from a predicted result ▪ Genetic drift is the change in allele frequencies that occurs by chance events. In essence, it is identical to the statistical phenomenon of sampling error on an evolutionary scale. ▪ It is a random process. ▪ Because sampling error is greatest in small samples and smallest in large samples, the strength of genetic drift increases as populations get smaller. Genetic Variations Classical and Population Genetics 129

126. Genetic Drift Classical and Population Genetics 130 It is a phenomenon that leads to random changes in the gene frequency in a founder population, which may not carry some alleles due to sampling error. Genetic drift leads to loss or fixation of alleles within populations. Genetic drift can irreversibly alter gene frequencies and eliminates alleles, which can decrease a populations ability to survive or to adapt to an altered environment, and it can preclude future selection.  

127. Fig 23.4 Genetic Drift in a small population of 10 individuals Genetic Drift Classical and Population Genetics 131

128.   Effects of Genetic  drift: • Populations lose genetic variation • With little variation, a population is less likely to have some individuals that will be able to adapt to a changing environment • Any lethal alleles may be carried in the population by heterozygous individuals, and become more common in the gene pool due to chance alone • significant in small populations • causes allele frequencies to change at random • can lead to a loss of genetic variation within populations • can cause harmful alleles to become fixed There are two types of Genetic Drift: 1. Bottleneck Effect 2. Founder Effect Genetic Variations Classical and Population Genetics 132

129.    1. The Bottleneck  Effect •  •• Bottleneck effect – A sudden decrease in population size to natural forces The random change in gene frequency found in small populations from generation to generation is called as ‘random genetic drift’. Random drift occurring independently in different sub-populations possess significantly different gene and genotype frequencies. Uniformity within sub-populations. Increased homozygosity sudden reduction in population size due to a change in the environment • New gene pool may not reflect original • If the population remains small, it may be further affected by genetic drift • Bottlenecks are periods of very low population size or near extinction. This is another special case of genetic drift. • The result of a population bottleneck is that even if the population regains its original numbers, genetic variation is drastically reduced Genetic Variations Classical and Population Genetics 133

130. Bottleneck - effect of a temporary period of small population size on allele frequencies Original population Genetic Drift Classical and Population Genetics 134

131. Some disaster strikes the original population …… Genetic Drift Classical and Population Genetics 136

132. Bottleneck effect Original population Disaster strikes Allele frequency has changed Genetic Drift Classical and Population Genetics 137

133. Bottleneck effect Original population After the disaster Allele frequency has changed Disaster strikes Genetic Drift Classical and Population Genetics 138

134. Genetic Drift Classical and Population Genetics 139

135. Genetic Drift Classical and Population Genetics 141

136. New habitat Founder effect Genetic Drift Classical and Population Genetics 142

137. The founders of the new population have a different allele frequency Founder effect Genetic Drift Classical and Population Genetics 143

138. Founder effect : the small initial number of Amish colonists included an individual carrying the recessive allele for six- fingered dwarfism Genetic Drift Classical and Population Genetics 144

139. Nonrandom Mating and Selection Classical and Population Genetics 146   • Mating that  occurs more or less frequently than expected by chance Mating among close relatives will lead to a surplus of homozygotes. Assortative mating – If individuals prefer to mate with other individuals with similar genotypes this may lead to a surplus of homozygotes. • Inbreeding – Mating with relatives – Increases homozygosity Nonrandom Mating • Out breeding – Mating with non-relatives – Increases heterozygosity   Disassortative mating - If individuals prefer to mate with other individuals with different genotypes, then this may lead to a surplus of heterozygotes. Wahlund effect – This denotes a surplus of homozygotes due to the presence of individuals that represent different populations and do not inter breed. It is defined as the non-random differential propagation of the genotypes. In other words. Selection acts on the phenotype of the next generation and is considered to select in favor by nature. One who contributes the highest number of progeny is called as the fittest individual. Has highest fitness (F=1). The change in gene frequency due to selection depends on the coefficient of selection or the degree of disadvantage of the phenotype and its frequency in the population.

140. The Paradox of Variation: Evolution requires natural selection, but natural selection eliminates variation. Genetic Variations Classical and Population Genetics 147

141. Forms of Selection Classical and Population Genetics 148 Three types of natural selection have been identified ◦ Stabilizing selection : Acts to eliminate both extreme phenotypes ◦ Disruptive selection : Acts to eliminate intermediate phenotypes ◦ Directional selection : Acts to eliminate a single extreme phenotype  

142. Selection Classical and Population Genetics 149   •Some individuals  leave behind more offspring than others • Artificial selection – Breeder selects for desired characteristics • Natural selection – Environment selects for adapted characteristics The  natural selection is a process by which heritable traits that makes it more likely for an organisms to survive and successfully reproduced become more common in population over successive generation.

143. The Paradox of Variation: Evolution requires natural selection, but natural selection eliminates variation. Genetic Variations Classical and Population Genetics 150

144. Artificial selection has produced different, true-breeding varieties of “fancy” pigeons from a single ancestral form Artificial Selection Classical and Population Genetics 151

145. Stabilizing Selection Classical and Population Genetics 152 Stabilizing Selection Its  a type of natural selection in which genetic diversity decreases as the population stabilizes on a particular trait value. Stabilizing selection act to keep a population well adapted to its environment . e.g. birth weight of human baby. the selection, describe  change in population genetics in which extreme value for trait are favor over intermediate values. • In the African seed-cracker finch, large- and small-beaked birds predominate

146. Selections Classical and Population Genetics 153 Disruptive Selection • Intermediate-beaked birds are at a disadvantage – Unable to open large seeds – Too clumsy to open small seeds More adept at handling small seeds Can open tough shells of large seeds • Direction selection  is a mode of natural selection in which a single phenotype is favored, causing the allele frequencies continuously shift in one direction. • E.g industrial melanism Directional Selection

147. Polymorphism Classical and Population Genetics 154 Grove snail: The grove snail, Cepaea nemoralis , is famous for the rich polymorphism of its shell. The system is controlled by a series of multiple alleles. The shell colour series is brown (genetically the top dominant trait), dark pink, light pink, very pale pink, dark yellow and light yellow (the bottom or universal recessive trait). Naturalists have  described phenotypic variation within many species. For example, All these sorts of phenotypic differences are called polymorphisms

148. Polymorphism Classical and Population Genetics 155 Chromosomal polymorphism Different  length of p-arms of acrocentric chromosomes Different extent of heterochromatin areas

149. Parent Offspring Traits are heritable Parent Offspring

150. Traits that enhance reproduction become more common each generation parents generation 1 offspring generation 1 parents generation 2 offspring generation 2

151. Inbreeding  Depression By Afshan Afareen Lectures no. 24 , 25

152. Increase in Homozygosity-  Classical and Population Genetics 159 .  Allele frequencies are constant at p=0.4 and q=0.6 over generations. Selfing reduces heterozygosity by a factor of ½ with each generation. This means inbreeding affects only relative proportions of genotype, not allele frequencies. Allele frequency is affected only by one of the four forces of evolution- mutation, migration, selection & genetic drift. The highest degree of inbreeding is achieved by selfing . Selfing reduces heterozygosity by a factor of ½ with each generation.

153. Inbreeding coefficient Classical and Population Genetics 161 Quantifying  heterozygosity genotype H in a random mating population, expected heterozygosity He, is the measure of inbreeding coeficient (f). f measures the fractional reduction in the heterozygosity relative to a random mating population with the same allele frequencies. f= (He – Ho)/ He. He= Expected frequency Ho= Observed frequency Interpretation: F = 0- no inbreeding F= 1, complete inbreeding Low F means less inbreeding ◦ High F means significant inbreeding

154. Inbreeding depression Classical and Population Genetics 162 Inbreeding depression is the reduced biological fitness in a given population as a result of inbreeding, or breeding of related individuals. It refers to decrease in fitness and vigour due to inbreeding or it may be defined as the reduction or loss in vigour and fertility as a result of inbreeding. Population biological fitness refers to an organism's ability to survive and perpetuate its genetic material. Inbreeding depression is often the result of a population bottleneck. In general, the higher the genetic variation or gene pool within a breeding population, the less likely it is to suffer from inbreeding depression.

155. Inbreeding depression Classical and Population Genetics 163 The most revealing impact of inbreeding is the loss of vigour and the physiological efficiency of an organism characterised by reduction in size and fecundity. The degree of inbreeding in any generation is equal to the degree of homozygosity in that generation. Inbreeding depression results due to fixation of unfavourable recessive genes in F2, while in heterosis the unfavourable recessive genes of one line (parent) are covered by favourable dominant genes of other parent.

156. Effect of Inbreeding  Classical and Population Genetics 164 Depression Inbreeding is due to a reduction in vigour and reproductive capacity that is fertility. There is a general reduction in the size of various plant parts and in yield. The effects of inbreeding may be summarised as under: a) Appearance of Lethal and Sublethal Alleles ◦ Inbreeding to the appearance of lethal, sublethal and subvital characteristics. ◦ Such characteristics include chlorophyll deficiencies e.g. Albino, chlorine rootles seedlings , defects in flower structure etc. generally, plants carrying such characteristics cannot maintained and are lost from the population. b) Reduction in Vigour ◦ There is a general reduction in the vigour of the population. ◦ Plants become shorter and weaker because of general reduction in the size of various plant parts.

157. Effect of Inbreeding  Classical and Population Genetics 165 c) Reduction in Reproductive Ability ◦ The reproductive ability of the population decreases rapidly. ◦ Many lines (plant progenies) reproduction poorly that they cannot be maintained. d) Separation of the Population into Distinct Lines ◦ The population rapidly separates into phenotypically distinct lines. ◦ This is because of an increase in homozygosity due to which there is random fixation of various alleles of different lines. ◦ Therefore, the lines differ in their genotype and consequently in phenotype. e) Increase in Homozygosity ◦ Each line becomes increasingly homozygous following inbreeding. ◦ Consequently, the variation within a line decreases rapidly. ◦ Ultimately, after 7 to 8 generations of selfing , the lines become almost uniform. ◦ Since they approach complete homozygosity (> 99 percent homozygosity).

158. Effect of Inbreeding  Classical and Population Genetics 166 ◦ The lines, which are almost homozygous due to continued inbreeding and are maintained through close inbreeding, are known as inbred lines or inbreds. Reduction in Yield ◦ Inbreeding generally leads to a loss in yield. ◦ The inbred lines that is able to survive and be maintained yield much less than the open pollinated varieties from which they were derived. ◦ In maize, the best – inbred lines yield about half as much as the open pollinated varieties from which they were produced. ◦ In alfalfa and carrot, the reduction in yields is much greater, while in onions and many cucurbits the reduction in yield is very small.

159. Degree of Inbreeding  Depression Classical and Population Genetics 167 The various plant species differ considerably in their responses to inbreeding. Inbreeding depression may range from very high to very low or may even be absent into the following four broad categories: ◦ High inbreeding depression ◦ Moderate inbreeding depression ◦ Low inbreeding depression ◦ Absence of inbreeding depression.

160. High Inbreeding  Depression Classical and Population Genetics 168 ◦ Several plant species, Eg. alfalfa (M. sativa) carrot (D. carota) , hayfield, tarweed etc show very high inbreeding depression. ◦ A large proportion of plants produced by selfing shows lethal characteristics and do not survive. ◦ The loss in vigour and fertility is so great that very few lines can be maintained after 3 to 4 generation of inbreeding. ◦ he line shows greatly reduced yields, generally less than 25 percent of the yield of open – pollinated varieties. Moderate Inbreeding Depression ◦ Many crops species, such as maize, jowar, bajara etc. shows moderate inbreeding depression. ◦ Many lethal and sublethal types appear in the selfed progeny, but a substantial proportion of the population can be maintained under self- pollination. ◦ There is appreciable reduction in fertility and many line reproduce so poorly that they are lost. ◦ However, a large number of inbred lines can be obtained, which yield upto 50 percent of the open- pollinated varieties.

161. Low Inbreeding  Depression Classical and Population Genetics 169 ◦ Several crop plants, E. g onion (A. cepa), many cucurbits, rye (S. cereale), sunflower ( Hannus ), hemp etc show only a small degree of inbreeding depression. ◦ Only a small proportion of the plants show lethal or subvital characteristics. ◦ The loss in vigour and fertility is small; rarely a line cannot be maintained due to poor fertility. ◦ The reduction in yield due to inbreeding is small or absent. ◦ Some of the inbreds lines may yields as much as the open pollinated varieties from which they were developed. Lack of inbreeding Depression ◦ The self- pollinated species do not show inbreeding depression although they do not show heterosis. ◦ It is because their species reproduce by self – fertilization and as a result, have developed homozygous balance. ◦ In cost of the cross- pollinated species exhibit heterozygous balance.

162. Heterosis By Dr. Afshan Afareen Lectures no. 26

163. Heterosis Classical and Population Genetics 171 Definition: Superiority of F1 hybrids over its parents. Hybrids are usually robust, vigorous, productive and taller. Term Dr. G. H.Shull (1914). Heteros mean Different and Osis mean Condition . Synonyms: 1. Hybrid Vigour 2. Outbreeding Enhancement

164. Classical and Population Genetics 172 Outbreeding Enhancement Heterosis is the opposite of inbreeding depression.  Inbreeding depression occurs when related parents have children with traits that negatively influence their fitness largely due to homozygosity. Outcrossing should result in heterosis. when a hybrid inherits traits from its parents that are not fully compatible, fitness can be reduced. This is a form of   outbreeding depression .

165. Classical and Population Genetics 173 Examples of Heterosis Hybrid Mule Hybrid Hen Hybrid Silk worm Hybrid Pig

166. Classical and Population Genetics 174 Types of Heterosis 1.True Heterosis 2.Pseudo-Heterosis Mutational True Heterosis It is the shadowing of the deleterious, unfavorable , recessive mutant genes by their adaptively superior dominant alleles. b) Balanced True Heterosis Balanced gene combinations with better adaptive value and agricultural usefulness.

167. Classical and Population Genetics 175 2.Pseudo Heterosis It is also called luxuriance. Crossing of the two parental forms brings in an accidental and un-adaptable expression of temporary vigour and vegetative overgrowth.

168. Classical and Population Genetics 176 Theories of Heterosis (I) Dominance Hypothesis (ii) Over-dominance Hypothesis

169. Classical and Population Genetics 177 Dominance Hypothesis Genes that are favorable for vigour and growth are dominant . Genes that are harmful to the individual are recessive. Dominant genes ABCDE are favorable for good yield. Inbred A x Inbred B AA BB cc dd aa bb CC DD F1 Hybrid A a B b C c D d Heterosis ∝ No of dominant genes

170. Classical and Population Genetics 178 Over Dominance Hypothesis Hypothesis was given by Shull and East independently. Hybrid vigour on the basis of heterozygosity is superior to homozygosity. Inbred A x Inbred B AA BB cc dd aa bb CC DD F1 hybrid A a B b C c D d

171. Classical and Population Genetics 179 Methods for Estimation of Heterosis Mid Parent Heterosis Better Parent Heterosis Standard Heterosis

172. Classical and Population Genetics 180 Methods for Estimation of Heterosis Mid Parent Heterosis When the heterosis is estimated over the mean value or average of the two parents is known as mid parent heterosis. It is also known as relative heterosis . Mid Parent Heterosis = ( F1 – MP ) / 100 x MP Better Parent Heterosis When Heterosis is estimated over better parent is known as better parent heterosis. It is also known as heterobeltiosis . Heterobeltiosis = ( F1 - BP ) / 100 x BP

173. Classical and Population Genetics 181 Methods for Estimation of Heterosis Standard Heterosis It refers to the superiority of F1 over the standard check variety. It is also known as economic heterosis. Heterosis leads to increase in yield, reproductive ability , vigor , quality. For most of characters , the desirable heterosis is positive. Standard Heterosis = ( F1 – Check ) / 100 x Check

174. Classical and Population Genetics 182 Significance of Heterosis Hybrids are vigorous, larger, healthier and faster growing than the parents. Hybrids usually have increased yield. Hybrids show improved quality Some hybrids show greater resistance to insects or diseases than parents. Hybrids are usually less susceptible to adverse environmental conditions. An increase in fertility and survival ability