1. Chapter 3. Mendelism: the Basic principles of Inheritance 1. Mendel’s Study of Heredity 2. Applications of Mendel’s Principles 3. Formulating and Testing Genetic Hypothesis 4. Mendelian Principles in Human Genetics 1

2. Mendel “Experiments in Plant Hybridization,” endeavored to explain how the characteristics of organisms are inherited. 2

3. Mendel performed experiments with several species of garden plants, and he even tried some experiments with honeybees. His greatest success, however, was with peas. Mendel’s 1866 Paper at the end of this chapter. Unfortunately, this paper languished in obscurity until 1900, when it was rediscovered by three botanists— Hugo de Vries in Holland, Carl Correns in Germany, and Eric von Tschermak-Seysenegg in Austria. 3

4. 1. Mendel’s Study of Heredity Gregor Johann Mendel (1822-1884) 1865 Garden pea Mendel's experimental organism, the garden pea (Pisum sativum) is a dicot plant that sprouts 2 leaves from the germinating seed 4

5. One peculiarity of pea reproduction is that the petals of the flower close down tightly, preventing pollen grains from entering or leaving. This enforces a system of self-fertilization, in which the male and female gametes from the same flower unite with each other to produce seeds. As a result, individual pea strains are highly inbred, displaying little if any genetic variation from one generation to the next. Because of this uniformity, we say that such strains are true-breeding 5

6. His 7 true-breeding traits: height, seed texture, seed color, pod shape, pod color, flower color, and flower position. Mendel took advantage of these contrasting traits to determine how the characteristics of pea plants are inherited. His focus on these singular differences between pea strains allowed him to study the inheritance of one trait at a time 6

7. Other biologists had attempted to follow the inheritance of many traits simultaneously but because the results of such experiments were complex, they were unable to discover any fundamental principles about heredity. 7

8. Monohybrid crosses Mendel cross-fertilized—or, simply, crossed—tall and dwarf pea plants to investigate how height was inherited monohybrid cross: A cross between parents differing in only one trait or in which only one trait is being considered. 8

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10. Mendel obtained tall plants regardless of the way he performed the cross (tall male with dwarf female or dwarf male with tall female); thus, the two reciprocal crosses gave the same results. Mendel noted that the dwarf characteristic seemed to have disappeared in the progeny of the cross, for all the hybrid plants were tall. 10

11. Mendel allowed them to undergo self-fertilization—the natural course of events in peas. When he examined the progeny, he found that they consisted of both tall and dwarf plants. In fact, among 1064 progeny that Mendel cultivated in his garden, 787 were tall and 277 were dwarf—a ratio of approximately 3:1. Mendel inferred that these hybrids carried a latent genetic factor for dwarfness, one that was masked by the expression of another factor for tallness. He said that the latent factor was recessive and that the expressed factor was dominant. 11

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13. Each trait that Mendel studied seemed to be controlled by a heritable factor that existed in two forms, one dominant, the other recessive. These factors are now called genes, a word coined by the Danish plant breeder Wilhelm Johannsen in 1909; their dominant and recessive forms are called alleles Alleles: One of a pair, or series, of alternative forms of a gene that occur at a given locus in a chromosome. Alleles are symbolized with the same basic symbol (for example, D for tall peas and d for dwarf). 13

14. another important conclusion: that genes come in pairs. Mendel proposed that each of the parental strains that he used in his experiments carried two identical copies of a gene—in modern terminology, they are diploid and homozygous. during the production of gametes, Mendel proposed that these two copies are reduced to one; that is, the gametes that emerge from meiosis carry a single copy of a gene—in modern terminology, they are haploid. 14

15. Mendel recognized that the diploid gene number would be restored when sperm and egg unite to form a zygote. Furthermore, he understood that if the sperm and egg came from genetically different plants—as they did in his crosses—the hybrid zygote would inherit two different alleles, one from the mother and one from the father. Such an offspring is said to be heterozygous. 15

16. he realized that random fertilizations with a mixed population of gametes—half carrying the dominant allele and half carrying the recessive allele— would produce some zygotes in which both alleles were recessive. Thus, he could explain the reappearance of the recessive characteristic in the progeny of the hybrid plants. 16

17. Mendel used symbols to represent the hereditary factors that he postulated—a methodological breakthrough. With symbols, he could describe hereditary phenomena clearly and concisely, and he could analyze the results of crosses mathematically. He could even make predictions about the outcome of future crosses. 17

18. The allelic constitution of each strain is said to be its genotype. By contrast, the physical appearance of each strain—the tall or dwarf characteristic—is said to be its phenotype. As the parental strains, the tall and dwarf pea plants form the P generation of the experiment. Their hybrid progeny are referred to as the first filial generation, or F 1 from a Latin word meaning “son” or “daughter.” Because each parent contributes equally to its offspring, the genotype of the plants must be Dd; that is, they are heterozygous for the alleles of the gene that controls plant height. 18

19. Mendel concluded—correctly—that the third that were true-breeding were DD homozygotes and that the two-thirds that were segregating were Dd heterozygotes. These proportions, and were exactly what his analysis predicted because, among the tall plants, the DD and Dd genotypes occur in a ratio of 1:2. 19

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21. 1.The Principle of Dominance: In a heterozygote, one allele may conceal the presence of another. This principle is a statement about genetic function. Some alleles evidently control the phenotype even when they are present in a single copy. 2. The Principle of Segregation: In a heterozygote, two different alleles segregate from each other during the formation of gametes. An allele is transmitted faithfully to the next generation, even if it was present with a different allele in a heterozygote. 21

22. Dihybrid Crosses: The Principle of Independent Assortment Mendel also performed experiments with plants that differed in two traits. The purpose of the experiments was to see if the two seed traits, color and texture, were inherited independently. 22

23. He crossed plants that produced yellow, round seeds with plants that produced green, wrinkled seeds. F1 seeds were all yellow and round, the alleles for these two characteristics were dominant. 23

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26. This analysis is predicated on two assumptions: (1) that each gene segregates its alleles, and (2) that these segregations are independent of each other. The second assumption implies that there is no connection or linkage between the segregation events of the two genes. For example, a gamete that receives W through the segregation of the texture gene is just as likely to receive G as it is to receive g through the segregation of the color gene. 26

27. 3. The Principle of Independent Assortment: The alleles of different genes segregate, or as we sometimes say, assort, independently of each other. 27

28. 1. Some alleles are dominant, others recessive - principle of dominance 2. During gamete formation, different alleles segregate from each other - principle of segregation 3. Different genes assort independently - principle of independent assortment 28

29. Do the experimental data fit with the predictions of our analysis? 29

30. 2. Applications of Mendel’s Principles If the genetic basis of a trait is known, Mendel’s principles can be used to predict the outcome of crosses. There are three general procedures, two relying on the systematic enumeration of all the zygotic genotypes or phenotypes and one relying on mathematical insight. The Punnett square method can be used for crosses involving 1 or 2 genes by writing down all possible gametes and systematically combining them in a grid-marked square. 30

31. ● The Punnett square method 31

32. The forked-line method is useful for crosses involving more than 2 genes and employs branching lines to tally the predicted outcomes of a trihybrid cross. The cross is arranged as 3 independent monohybrid crosses each producing 3:1 ratios of dominant to recessive traits and the cross has 3 branches. 32

33. ● The Forked-line method 33

34. testcross Backcross to the recessive parental type, or a cross between genetically unknown individuals with a fully recessive tester to determine whether an individual in question is heterozygous or homozygous for a certain allele. It is also used as a test for linkage. 34

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36. The quickest is the probability method because Mendelian segregation in heterozygotes is like a coin toss: half of the gametes contain one allele and the other half the other allele. The probability of producing an A or a gamete when Aa heterozygotes are crossed is 1/2. Therefore the probability of AA offspring = 1/2 x 1/2 = 1/4; similarly for aa progeny. Heterozygotes are 1/4 + 1/4 because the gametes can combine in two ways (aA and Aa). 36

37. ● The probability method 37

38. In multifactorial crosses involving, say, 4 genes, the probability methods yield quick answers. For example, a quadruple recessive homozygote would arise 1/4 x 1/4 x 1/4 x 1/4 = 1/256 of offspring. Surely, using the probability method is a better approach than diagramming a Punnett square with 256 entries! 38

39. What fraction of the offspring will be homozygous for all four genes? Before computing any probabilities, we must first decide what genotypes satisfy the question. For each gene there are two types of homozygotes, the dominant and the recessive, and together they constitute half the progeny. The fraction of progeny that will be homozygous for all four genes will therefore be (1/2) x (1/2) x (1/2) x (1/2) = (1/16) 39

40. Suppose the cross is AaBb x AaBb and we want to know what fraction of the progeny will show the recessive phenotype for at least one gene Three kinds of genotypes would satisfy this condition: (1) A- bb (the dash stands for either A or a), (2) aa B-, and (3) aa bb. 40

41. ● The probability method 41

42. 3. Formulating & Testing Genetic Hypothesis The chi-square (χ2) test is used to determine whether data support a particular hypothesis. To determine whether observed data from a monohybrid cross match those expected by Mendelian principles of segregation, we would: -Calculate the expected number of offspring for each phenotypic class from the sample size. -Square the difference between observed and expected numbers and divide by expected number of offspring. -Sum all terms and compare to the χ2 statistic. The hypothesis is regarded as true if there is less than a 5% likelihood that the observed differences arose by chance alone. 42

43. Snapdragons, Antirrhinum majus 43

44. The chi-square test: is a simple way of evaluating whether the prediction of a genetic hypothesis agree with data from an experiment 44

45. there are many such distributions, and to select the appropriate one, we need to know the degrees of freedom associated with the statistic. This index to the set of distributions is determined by subtracting one from the number of phenotypic classes; 45

46. ● The chi-square test 46

47. 4. Mendel’s Principles in Human Genetics Mendel’s principles can be applied to study the inheritance of traits in humans. However, because it is not possible to make controlled crosses with human beings, progress was obviously slow. The genetic analysis of human heredity depends on family records, which are often incomplete. In addition, human beings—unlike experimental organisms—do not produce many progeny, 47

48. Pedigrees diagram the relationships among family members where squares designate males and circles designate females, a horizontal line represents mating and vertical lines beneath reflect offspring. Birth order is left to right, afflicted individuals are shaded or filled in 48

49. generation denoted by Roman numerals. An underlying assumption is that mutations arise at a very low rate (one in a million or so). - For a dominant trait, every afflicted person should have an afflicted parent. 49

50. Pedigrees : are used to identify dominant and recessive traits in human families 50

51. A recessive trait will often skip generations and afflicted offspring often do not have an afflicted parent. 51

52. 52 Achondroplasia (dwarfism)Albinism (lack of pigment)

53. 53 Bald-headed

54. 54 Brachidactyly (Short fingers )

55. 55 Wooly hair

56. 56 Neurofibromatosis(tumorlike growth in the body)

57. Mendelian Segregation in Human Families In human beings, the number of children produced by a couple is typically small. Such numbers provide nothing close to the statistical power that Mendel had in his experiments with peas. Consequently, phenotypic ratios in human families often deviate significantly from their Mendelian expectations. 57

58. As an example, let us consider a couple who are each heterozygous for a recessive allele that, in homozygous condition, causes cystic fibrosis. If the couple were to have four children, would we expect exactly three to be unaffected and one to be affected by cystic fibrosis? 58

59. Although this is a possible outcome, it is not the only one. There are, in fact, five distinct possibilities: 1. Four unaffected, none affected. 2. Three unaffected, one affected. 3. Two unaffected, two affected. 4. One unaffected, three affected. 5. None unaffected, four affected. Intuitively, the second outcome seems to be the most likely, since it conforms to Mendel’s 3:1 ratio. 59

60. by using Mendel’s principles and by treating each birth as an independent event, For a particular birth, the chance that the child will be unaffected is 3/4 60

61. The outcome of three unaffected children and one affected child, for instance, comprises four distinct events; if we let U symbolize an unaffected child and A an affected child, and if we write the children in their order of birth, we can represent these events as UUUA, UUAU, UAUU, and AUUU 61

62. Mendelian segregation in human families 62

63. Genetic Counseling The diagnosis of genetic conditions is often a difficult process. Prospective parents may want to know whether their children are at risk to inherit a particular condition. As an example, let’s consider a pedigree showing the inheritance of nonpolypoid colorectal cancer. This disease is one of several types of cancer that are inherited. 63

64. It is due to a dominant mutation that affects about 1 in 500 individuals in the general population. the cancer is manifested in at least one individual in each generation and every affected individual has an affected parent. The counseling issue arises in generation V. Among the nine individuals shown, two are affected and seven are not. 64

65. some of these seven unaffected individuals may have inherited the mutation and would therefore be at risk to develop nonpolypoid colorectal cancer later in life. Only time will tell. the longer they remain unaffected, the greater the probability that they are actually not carriers. Each of the seven unaffected individuals will, of course, have to live with the anxiety of being a possible carrier of the cancer-causing mutation. Furthermore, at some point they will have to decide if they wish to reproduce and risk transmitting the mutation to their children. 65

66. As another example, A couple, denoted R and S is concerned about the possibility that they will have a child (T) with albinism, an autosomal recessive condition characterized by a complete absence of melanin pigment in the skin, eyes, and hair. 66

67. To determine the first probability, we need to consider the possible genotypes for R. One of these, that he is homozygous for the recessive allele (aa), is excluded because we know that he does not have albinism himself. However, the other two genotypes, AA and Aa, remain distinct possibilities. To calculate the probabilities associated with each of these, we note that both of R’s parents must be heterozygotes, because they have had two children with albinism. The mating that produced R was therefore Aa x Aa 67

68. we would expect 2/3 of the offspring without albinism to be Aa and 1/3 to be AA the probability that R is a heterozygous carrier of the albinism allele is 2/3. To determine the probability that he will transmit this allele to his child, we simply note that a will be present in half of his gametes. 68

69. Risk that T is aa = (probability that R is Aa) × (probability that R transmits a, assuming that R is Aa) = (2/3) × (1/2) = (1/3) 69