Peter J Russell CHAPTER 10 Mendelian Genetics edited

Peter J. Russell CHAPTER 10 Mendelian Genetics edited by Yue-Wen Wang Ph. D. Dept. of Agronomy, 台大農藝系 NTU 遺傳學 601 20000 1

Introduction 1. Gregor Mendel (1822– 1884) laid the foundation for our current understanding of heredity. 2. Mendel did not know about chromosomes or genes, which were discovered after his lifetime. 台大農藝系 遺傳學 601 20000 2

Genotype and Phenotype 1. Hereditary traits are under control of genes (Mendel called them particulate factors). 2. Genotype is the genetic makeup of an organism, a description of the genes it contains. 3. Phenotype is the characteristics that can be observed in an organism. 4. Phenotype is determined by interaction of genes and environment. Genes provide potential, but environment determines whether that potential is realized 台大農藝系 遺傳學 601 20000 3

Fig. 10. 1 Influences on the physical manifestation (phenotype) of the genetic blueprint (genotype) Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 4

Mendel’s Experimental Design 1. Mendel began his work in 1854 with the garden pea Pisum sativum, by crossbreeding plants with different characteristics. He reported his theory explaining transmission of traits to the next generation in 1865, but its significance was not realized until several decades later. 2. His success resulted from focusing on well-defined traits one at a time, quantifying the offspring and analyzing the results mathematically. 3. Garden peas are excellent for this type of research, because they grow easily, produce large numbers of seeds quickly and routinely self-fertilize. Experimental cross-fertilization is also readily accomplished in peas. 4. Mendel first grew strains of peas using self-fertilization to be certain that the traits of interest were unchanged in subsequent generations (true-breeding or pure-breeding strains). 5. Then he looked at inheritance of traits selected because they have only two distinct possibilities for phenotype. The traits he studied are listed, and the dominant phenotype is indicated by an asterisk: a. Flower/seed coat color (one gene controls both): *grey/purple vs. white/white. b. Seed color: *yellow vs. green. c. Seed shape: *green vs. yellow. d. Pod color: *green vs. yellow. e. Pod shape: *inflated vs. pinched. f. Stem height: *tall vs. short. g. Flower position: *axial vs. terminal. 台大農藝系 遺傳學 601 20000 5

Fig. 10. 3 Procedure for crossing pea plants Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 6

Fig. 10. 4 Seven character pairs in the garden pea that Mendel studied in his breeding experiments Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 7

Monohybrid Crosses and Mendel’s Principle of Segregation 1. Terminology used in breeding experiments: a. Parental generation is the P generation. b. Progeny of P generation is the first filial generation, designated F 1. c. When F 1 interbreed, the second filial generation, F 2, is produced. d. Subsequent interbreeding produces F 3, F 4 and F 5 generations. 2. A monohybrid cross involves true-breeding strains that differ in a single trait. 3. To determine whether both parents contribute equally to the phenotype of a particular trait in offspring, a set of reciprocal crosses is performed. By convention, the female parent is given first. 4. In Mendelian genetics, offspring of a monohybrid cross will exactly resemble only one of the parents. This is the principle of uniformity in F 1. 5. Traits that disappear in the F 1 reappear in the F 2. The F 2 generation will have a ratio of about one individual with the “reappearing” phenotype to three individuals with the phenotype that was present in the F 1. Mendel reasoned that information to create the trait was present in the F 1 in the form of “particulate factors, ” which we now call genes (Figure 10. 6). 台大農藝系 遺傳學 601 20000 8

Fig. 10. 5 Results of one of Mendel’s breeding crosses Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 9

Fig. 10. 6 The F 2 progeny of the cross shown in Figure 10. 5 Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 10

6. Each particulate factor exists in alternative forms (now called alleles) that control a specific trait. True-breeding strains contain identical factors. The F 1 contain one of each, but since the trait is just like one of the parents rather than a mix, one (dominant) allele has masked expression of the other (recessive) one. 7. By convention, letters may be used to designate alleles, with the dominant a capital letter (S), and the recessive in lower case (s). 8. Individuals with identical alleles (e. g. , genotypes SS and ss) are called homozygous for that gene, because all their gametes will have the same allele for this trait. Individuals with different alleles (e. g. , Ss) are heterozygous, because 1⁄2 of their gametes will contain one allele, and 1⁄2 the other (Figure 10. 7). 台大農藝系 遺傳學 601 20000 11

Fig. 10. 7 Dominant and recessive alleles of a gene for seed shape in peas Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 12

9. Diagrams of a smooth x wrinkled cross appear in Figure 10. 8. The Punnett square is a diagram showing all possible combinations of the gametes produced by each parent. Note that it accounts for the 3: 1 ratio in the F 2 generation. 10. When Mendel had conducted experiments for the seven different traits in garden peas, he made these conclusions: a. Results of reciprocal crosses are always the same. b. The F 1 resembled only one of the parents. c. The trait missing in the F 1 reappeared in about 1⁄4 of the F 2 individuals. 台大農藝系 遺傳學 601 20000 13

Fig. 10. 8 a Mendel’s first law, principle of segregation of Mendelian factors: Production of the F 1 generation Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 14

Fig. 10. 8 b Mendel’s first law, principle of segregation of Mendelian factors: Production of the F 2 generation Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 15

The Principle of Segregation Animation: Mendel's Principle of Segregation 1. The first Mendelian law, the principle of segregation, states: “Recessive characters, which are masked in the F 1 from a cross between two true-breeding strains, reappear in a specific proportion in the F 2. ” This is because alleles segregate during anaphase I of meiosis, and progeny are then produced by random combination of the gametes. 2. A summary of terms and concepts appears in Box 10. 1 台大農藝系 遺傳學 601 20000 16

Representing Crosses with a Branch Diagram • 1. The branch diagram is an alternative approach to predicting the outcome of crosses (Box 10. 2 and Figure 10. 9). • 2. Results from a branch diagram will be identical to those obtained with a Punnett square. 台大農藝系 遺傳學 601 20000 17

Fig. 10. 9 Using the branch diagram approach to calculate the ratios of phenotypes in the F 2 generation of the cross in Figure 10. 8 Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 18

Confirming the Principle of Segregation: The Use of Testcrosses 1. Mendel observed that plants with the recessive phenotype are all true-breeding. When plants with the dominant phenotype are selfed, 1⁄3 are truebreeding, and 2⁄3 produce progeny with both phenotypes. 2. A more common method to determine whether an individual with the dominant phenotype is homozygous or heterozygous is to perform a testcross by crossing the individual with one that is homozygous recessive. 台大農藝系 遺傳學 601 20000 19

Fig. 10 Determining the genotypes of the F 2 smooth progeny of Figure 10. 8 by selfing the plants grown from the smooth seeds Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 20

Fig. 10. 11 Determination of F 2 smooth seeds’ genotype by testcrossing to a wrinkledseed plant Peter J. Russell, i. Genetics: Copyright © Pearson Education, Inc. , publishing as Benjamin Cummings. 台大農藝系 遺傳學 601 20000 21

Dihybrid Crosses and Mendel’s Principle of Independent Assortment The Principle of Independent Assortment Animation: Mendel's Principle of Independent Assortment 1. After Mendel analyzed crosses involving two pairs of traits (dihybrid crosses), he formulated his second law, the principle of independent assortment, which says that the factors for different traits assort independently of one another. This allows for new combinations of the traits in the offspring. 2. A dihybrid cross will produce four possible phenotypic classes, in a 9: 3: 3: 1 ratio. 台大農藝系 遺傳學 601 20000 22

Branch Diagram of Dihybrid Crosses 1. Dihybrid crosses can be represented with either a Punnett square or a branch diagram. With practice, the student should be able to calculate results of crosses simply by applying Mendelian principles (Figure 10. 13). 2. Individuals of unknown genotype that show the dominant phenotype can be represented by a dominant allele and a dash (e. g. , S-) to indicate that the second allele is unknown. 3. If alleles assort independently, all possible phenotypes will be represented in the F 2, in a ratio of 9: 3: 3: 1. If the F 1 are test crossed, all types of offspring in a ratio of 1: 1: 1: 1 will be produced (Figure 10. 12). 4. In the F 2 of a dihybrid cross there will be four phenotypic classes, and nine genotypic classes (Table 10. 2) 台大農藝系 遺傳學 601 20000 23

Fig. 10. 12 a Principle of independent assortment: Production of the F 1 generation 台大農藝系 遺傳學 601 20000 24

Fig. 10. 12 b Derivation of F 2 genotypes and 9: 3: 3: 1 phenotypic ratio by use of the Punnett square 台大農藝系 遺傳學 601 20000 25

Fig. 10. 13 Using the branch diagram approach to calculate the F 2 phenotypic ratio of the cross in Figure 10. 12 台大農藝系 遺傳學 601 20000 26

i. Activity: Tribble Traits 台大農藝系 遺傳學 601 20000 27

Trihybrid Crosses 1. Crosses involving three independently assorting character pairs are called trihybrid. There are 64 possible combinations of the eight different gamete types contributed by each parent, creating 27 different genotypes. There will be eight different phenotypes, in a predicted ratio of 27: 9: 9: 9: 3: 3: 3: 1. 2. Some useful generalizations about Mendelian genetics, with the following assumptions: (1) The parents are two different true-breeding strains for the gene(s) under study; (2) The F 1 self-fertilize or interbreed. Under these assumptions: a. The F 1 will be heterozygous for each gene involved in the cross. b. When the F 1 interbreed, the F 2 will contain 3⁄4 dominant phenotype and 1⁄4 recessive phenotype individuals, with genotype frequencies of 1⁄4 for AA, 1⁄2 for Aa, and 1⁄4 for aa. c. There are two phenotypic classes in the F 2 of a monohybrid cross, four in a dihybrid cross and eight in a trihybrid cross. General rule is that there are 2 n phenotypic classes in the F 2, where n is the number of independently assorting heterozygous gene pairs. d. There are three genotypic classes in the F 2 of a monohybrid cross, while there are nine in a dihybrid cross and 27 in a trihybrid cross. General rule is that there are 3 n phenotypic classes in the F 2, where n is the number of independently assorting heterozygous gene pairs. e. The phenotypic rule (2 n) is also used to predict the number of genotypic classes produced in the test cross of a multiply heterozygous , because the number of 台大農藝系F 1遺傳學 601 20000 genotypic classes will match the number of phenotypic ones. 28

Fig. 10. 14 Branch diagram derivation of the relative frequencies of the eight phenotypic classes in the F 2 of a trihybrid cross 台大農藝系 遺傳學 601 20000 29

The “Rediscovery” of Mendel’s Principles 1. Mendel’s work was published in 1866, but received little attention from the scientific community until about 1900. 2. In 1902, William Bateson, experimenting with fowl, showed that Mendelian principles apply in animals. He coined the terms genetics, zygote, F 1, F 2, and allelomorph (which was shortened to allele). W. L. Johannsen named Mendelian factors genes in 1909. 台大農藝系 遺傳學 601 20000 31

Statistical Analysis of Genetic Data: The Chi. Square Test 1. One of the advantages of the Mendelian approach is that it is quantitative and may be tested mathematically. A hypothesis is presented as a null hypothesis, proposing that the observed data are the same as the predicted results. 2. A chi-square (χ2) test checks for goodness-of fit between the expected and observed results, to determine whether differences are likely to be due to chance alone. 3. See Tables 10. 2 and 10. 4 for an example using the chi-square test to analyze a hypothesis. 4. Chi-square analysis cannot tell us that a hypothesis is correct or incorrect, only whether the observed result is a good fit with predictions of the hypothesis. a. If differences between the results and the prediction are unlikely to be due to chance alone, the hypothesis will be rejected another one tried. b. Typically if the probability of obtaining the observed χ2 values is greater than 5% (P> 0. 05) the hypothesis is not遺傳學 rejected. 台大農藝系 601 20000 32

Mendelian Genetics in Humans 1. W. Farabee in 1905 was the first to demonstrate Mendelian principles in humans, showing that brachydactyly is inherited as a simple dominant trait. 台大農藝系 遺傳學 601 20000 35

Pedigree Analysis 1. The study of the phenotypic records of a family over several generations is pedigree analysis. The individual upon whom the study focuses is the propositus (male) or proposita (female). 2. The symbols of pedigree analysis are summarized in Figure 10. 16, and Figure 10. 17 shows a sample pedigree. Note that generations are numbered with Roman numerals while individuals are numbered with Arabic numerals. 台大農藝系 遺傳學 601 20000 36

Fig. 10. 16 Symbols used in human pedigree analysis 台大農藝系 遺傳學 601 20000 37

Fig. 10. 17 Example of a human pedigree 台大農藝系 遺傳學 601 20000 38

Examples of Human Genetic Traits 1. Recessive traits are well documented in humans, and are usually the result of a mutation causing loss or modification of a gene product. Albinism (Figure 10. 18) is an example. 2. Deleterious recessive alleles persist in the population because heterozygous individuals carry the allele without developing the phenotype, and so are not at a selective disadvantage. 3. Characteristics of recessive inheritance of a relatively rare trait: a. Parents of most affected individuals have normal phenotypes but are heterozygous. If the allele is rare the trait will “skip” generations. b. Mating of heterozygotes will produce 3⁄4 normal progeny and 1⁄4 with the recessive phenotype. c. If both parents have the recessive trait, all their progeny will usually also have the trait. 台大農藝系 遺傳學 601 20000 39

Fig. 10. 18 Albinism (a) Two individuals with albinism: blue musicians Johnny (left) and Edgar Winter (right) (b) A pedigree showing the transmission of the autosomal recessive trait of albinism 台大農藝系 遺傳學 601 20000 40

4. Dominant traits are also well documented in humans. A mutation may produce a dominant phenotype by causing a function to be gained due to an altered gene product capable of a new activity. Examples: a. Woolly hair (Figure 10. 19). b. Achondroplasia. c. Brachydactyly. d. Marfan syndrome. 5. Dominant alleles produce a distinct phenotype when in a heterozygote whose other allele is wild-type. Due to the rarity of dominant mutant alleles causing recognizable traits, homozygous dominant individuals are very unusual. Most pairings are between a heterozygote and a homozygous recessive (wild-type) individual. 6. Characteristics of dominant inheritance of a relatively rare trait: a. Affected individuals have at least one affected parent. b. The trait is present in every generation. c. Offspring of an affected heterozygote will be 1⁄2 affected and 1⁄2 wildtype. 台大農藝系 遺傳學 601 20000 41

Fig. 10. 19 Woolly hair (a) Members of a Norwegian family, some of whom exhinbit the trait of woolly hair (b) Part of a pedigree showing the transmission of the autosomal dominant trait of woolly hair 台大農藝系 遺傳學 601 20000 42