Lecture 1 Mendelian Genetics PDF

Mendelian Genetics Chapter 2  Mystery of heredity 2  Before the 20th century, 2 concepts were the basis for ideas about heredity  Heredity occurs within species  Traits are transmitted directly from parent to offspring  Thought traits were borne throu...

Mendelian Genetics Chapter 2  Mystery of heredity 2  Before the 20th century, 2 concepts were the basis for ideas about heredity  Heredity occurs within species  Traits are transmitted directly from parent to offspring  Thought traits were borne through fluid and blended in offspring  Paradox – if blending occurs why don’t all individuals look alike? Blending theory of inheritance Factors that control hereditary traits are malleable They can blend together from generation to generation Gregor Mendel’s pioneering experiments with garden peas refuted all of the above! © McGraw-Hill Education. 2-3 Mendel’s Study of Pea Plants Gregor Johann Mendel (1822-1884) is considered the father of genetics His success can be attributed, in part, to His boyhood experience in grafting trees  This taught him the importance of precision and attention to detail His university experience in physics and natural history  This taught him to view the world as an orderly place governed by natural laws These laws can be stated mathematically © McGraw-Hill Education. 2-5  Mendel’s Laws of Inheritance Mendel was an Austrian monk He conducted his landmark studies in a small 115- by 23-foot plot in the garden of his monastery From 1856-1864, he performed thousands of crosses He kept meticulously accurate records that included quantitative analysis © McGraw-Hill Education. 2-6 Mendel’s Laws of Inheritance His work, entitled “Experiments on Plant Hybrids” was published in 1866 It was ignored for 34 years Probably because The title did not capture the importance of the work Lack of understanding of chromosome transmission © McGraw-Hill Education. 2-7  Mendel’s Laws of Inheritance In 1900, Mendel’s work was rediscovered by three botanists working independently Hugo de Vries of Holland Carl Correns of Germany Erich von Tschermak of Austria © McGraw-Hill Education. 2-8 Mendel Chose Pea Plants as His Experimental Organism Hybridization The mating or crossing between two individuals that have different characteristics Purple-flowered plant X white-flowered plant Hybrids The offspring that result from such a mating © McGraw-Hill Education. 2-9 Mendel Chose Pea Plants as His Experimental Organism Mendel chose the garden pea (Pisum sativum) to study the natural laws governing plants hybrids The garden pea was advantageous because It existed in several varieties with distinct characteristics Its structure allowed for easy crosses where the choice of parental plants could be controlled © McGraw-Hill Education. 2-10 Mendel Chose Pea Plants as His Experimental Organism Mendel carried out two types of crosses Self-fertilization Pollen and egg are derived from the same plant Naturally occurs in peas because a modified petal isolates the reproductive structures Cross-fertilization Pollen and egg are derived from different plants Required removing and manipulating anthers Refer to Figure 2.3 © McGraw-Hill Education. 2-11 A picture of his original work Structure of a Pea Flower 2.2a (a) Structure of a pea flower © McGraw-Hill Education. 2-13 Pollination and Fertilization in Angiosperms (c) Pollination and fertilization in angiosperms © McGraw-Hill Education. 2-14 How Mendel Crossed Fertilized Peas © McGraw-Hill Education. 2-15 Cross-pollination or Cross-Fertilization Mendel Studied Seven Characters that Bred True The morphological characteristics of an organism are termed characters The term trait describes the specific properties of a character eye color is a character, blue eyes is a trait A variety that produces the same trait over several generations is termed a true-breeder The seven characters that Mendel studied are illustrated in Figure 2.4 © McGraw-Hill Education. 2-17 Seven Characters Mendel Studied © McGraw-Hill Education. 2-18 Mendel’s Experiments Mendel did not have a hypothesis to explain the formation of hybrids Rather, he believed that a quantitative analysis of crosses may provide mathematical relationships that govern hereditary traits This is called an empirical approach This approach is used to deduce empirical laws © McGraw-Hill Education. 2-19 Mendel’s Experiments Mendel studied seven characteristics Each characteristic showed two variants found in the same species plant height variants were tall and dwarf His first experiments involved crossing two variants of the same characteristic This is termed a monohybrid cross A single characteristic is being observed The experimental procedure is shown in Figure 2.5 © McGraw-Hill Education. 2-20 Mendel’s Experiments Mendel also performed dihybrid crosses Crossing individual plants that differ in two characters For example Character 1 = Seed texture (round vs. wrinkled) Character 2 = Seed color (yellow vs. green) There are two possible patterns of inheritance for these characters Refer to Figure 2.7 The experimental procedure for the dihybrid cross is shown in Figure 2-8 © McGraw-Hill Education. 2-21 Single Factor Crosses 1. For each of seven characters, Mendel cross-fertilized two different true breeding strains. Keep in mind that each cross involved in two plants that differed in regard to only one of the seven characters studied. The illustration at the right shows one cross between a tall and dwarf plant. This is called a P (parental) cross. 2. Collect the F1 generation seeds. The following spring, plant the seeds and allow the plants to grow. These are the plants of the F1 generation. 3. Allow the F1 generation plants to self-fertilize. This produces seeds that are part of the F2 generation. © McGraw-Hill Education. 2-22 Single Factor Crosses 4. Collect the F2 generation seeds and plant them the following spring to obtain the F2 generation plants. 5. Analyze the traits found in each generation. © McGraw-Hill Education. 2-23  Mendel’s Data 1. Crossed true-breeding plants differing at one of seven traits. 2. Crossed hybrid offspring to each other (all show dominant trait). 3. Counted offspring of hybrid crosses. Ratio # with # with Dominant : Trait Offspring dominant trait recessive trait recessive Seed form 7,324 5,474 1,850 2.96 : 1 Seed color 8,023 6,022 2,001 3.01 : 1 Seed coat color 929 705 224 3.15 : 1 Pod form 1,181 882 299 2.95 : 1 Pod color 580 428 152 2.82 : 1 Flower position 858 651 207 3.14 : 1 Stem length 1,064 787 277 2.84 : 1 Interpreting the Data For all seven characteristics studied The F1 generation showed only one of the two parental traits The F2 generation showed an ~ 3:1 ratio of the two parental traits These results refuted a blending mechanism of heredity © McGraw-Hill Education. 2-25 Interpreting the Data Indeed, the data suggested a particulate theory of inheritance Mendel postulated the following: A pea plant contains two discrete hereditary factors for a given character, one from each parent The two factors may be identical or different © McGraw-Hill Education. 2-26 Interpreting the Data When the two factors of a single character are different and present in the same plant One variant is dominant and its effect can be seen The other variant is recessive and is not seen Particulate theory of inheritance : the genetic determinants that govern traits are inherited as discrete units that remain unchanged as they are passed from parent to offspring © McGraw-Hill Education. 2-27 Interpreting the Data During gamete formation, the paired factors for a given character segregate randomly so that half of the gametes receive one factor and half of the gametes receive the other This is Mendel’s Law of Segregation Refer to Figure 2.6 © McGraw-Hill Education. 2-28 Mendel’s 3:1 Ratio Is Consistent with the Law of Segregation But first, let’s introduce a few terms Mendelian factors are now called genes Alleles are different versions of the same gene An individual with two identical alleles is termed homozygous An individual with two different alleles, is termed heterozygous Genotype refers to the specific allelic composition of an individual Phenotype refers to the outward appearance of an individual © McGraw-Hill Education. 2-29 30 Principle of Segregation  Two alleles for a gene segregate during gamete formation and are rejoined at random, one from each parent, during fertilization  Physical basis for allele segregation is the behavior of chromosomes during meiosis  Mendel had no knowledge of chromosomes or meiosis – had not yet been described Mendel's Law of Segregation © McGraw-Hill Education. 2-31 Punnett Squares A Punnett square is a grid that enables one to predict the outcome of simple genetic crosses It was proposed by the English geneticist, Reginald Punnett We will illustrate the Punnett square approach using the cross of heterozygous tall plants as an example © McGraw-Hill Education. 2-32 Punnett Squares Write down the genotypes of both parents Male parent = Tt Female parent = Tt Write down the possible gametes each parent can make. Male gametes: T or t Female gametes: T or t © McGraw-Hill Education. 2-33 Punnett Squares Fill in the Punnett square with the possible genotypes of the offspring by combining the alleles of the gametes © McGraw-Hill Education. 2-34 Two Different Genes Assort Figure (a) HYPOTHESIS: Linked assortment © McGraw-Hill Education. 2-35 Two Different Genes Assort Figure (b) HYPOTHESIS: Independent assortment © McGraw-Hill Education. 2-36 Mendel’s Second Law of Independent Assortment 1. Two genes on different chromosomes segregate their alleles independently. 2. The inheritance of an allele of one gene does not influence which allele is inherited at a second gene. 38 Principle of independent assortment 1. In a dihybrid cross, the alleles of each gene assort independently 2. The segregation of different allele pairs is independent 3. Independent alignment of different homologous chromosome pairs during metaphase I leads to the independent segregation of the different allele pairs Independent Assortment of Two Traits  In a dihybrid cross, parents with two differing traits are crossed.  Which allele is dominant? Heterozygous peas are round and yellow. Therefore round is dominant to wrinkled yellow is dominant to green 40 F1 self-fertilizes RrYy x RrYy The F2 generation shows all four possible phenotypes in a set ratio  9:3:3:1  R_Y_:R_yy:rrY_:rryy  Round yellow:round green:wrinkled yellow:wrinkled green 41 42 MODERN GENETICS  Defective copy of a gene  Pedigree analysis is used to determine inheritance pattern Symbols Used in Pedigree Analysis (b) Symbols used in a human pedigree © McGraw-Hill Education. 2-45 Human Pedigree Showing Cystic Fibrosis (a) Human pedigree showing cystic fibrosis © McGraw-Hill Education. 2-46 Pedigree Analysis (1 of 2) Pedigree analysis is commonly used to determine the inheritance pattern of human genetic diseases Genes that play a role in disease may exist as A normal allele A mutant allele that causes disease symptoms Diseases that follow a simple Mendelian pattern of inheritance can be Dominant Recessive © McGraw-Hill Education. 2-47 Pedigree Analysis (2 of 2) A recessive pattern of inheritance makes two important predictions Two normal heterozygous individuals will have, on average, 25% of their offspring affected Two affected individuals will produce 100% affected offspring A dominant pattern of inheritance predicts that An affected individual will have inherited the gene from at least one affected parent Alternatively, the disease may have been the result of a new mutation that occurred during gamete formation © McGraw-Hill Education. 2-48 Cystic Fibrosis (CF) Cystic fibrosis (CF) A recessive disorder of humans About 3% of Caucasians are carriers The gene encodes a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) The CFTR protein regulates ion transport across the cell membrane The mutant allele creates an altered CFTR protein that ultimately causes ion imbalance This leads to abnormalities in the pancreas, intestine, sweat glands and lungs © McGraw-Hill Education. 2-49 Probability (1 of 3) The probability of an event is the chance that the event will occur in the future Number of times an event occurs Probability  Total number of events For example, in a coin flip Pheads  1 heads 1 heads  1 tails   1 2  50 % © McGraw-Hill Education. 2-50 Probability (2 of 3) The accuracy of the probability prediction depends largely on the size of the sample Often, there is deviation between observed and expected outcomes This is due to random sampling error Random sampling error is large for small samples and small for large samples For example If a coin is flipped only 10 times It is not unusual to get 70% heads and 30% tails © McGraw-Hill Education. 2-51 Probability (3 of 3) However, if the coin is flipped 1,000 times The percentage of heads will be fairly close to the predicted 50% value Probability calculations are used in genetic problems to predict the outcome of crosses To compute probability, we can use two mathematical operations Product rule Binomial expansion equation © McGraw-Hill Education. 2-52 Product Rule (1 of 3) The probability that two or more independent events will occur is equal to the product of their respective probabilities Note Independent events are those in which the occurrence of one does not affect the probability of another © McGraw-Hill Education. 2-53 Product Rule (2 of 3) Consider the disease congenital analgesia Recessive trait in humans Affected individuals can distinguish between sensations However, extreme sensations are not perceived as painful Two alleles P = Normal allele p = Congenital analgesia © McGraw-Hill Education. 2-54 Product Rule (3 of 3) Question Two heterozygous individuals plan to start a family What is the probability that the couple’s first three children will all have congenital analgesia? © McGraw-Hill Education. 2-55 Applying the Product Rule Step 1: Calculate the individual probabilities This can be obtained via a Punnett square Pcongenital analgesia   1 4 Step 2: Multiply the individual probabilities 1/4 × 1/4 × 1/4 × 1/64 1/16 can be converted to 0.016 Therefore 1.6% of the time, the first three offspring of a heterozygous couple, will all have congenital analgesia © McGraw-Hill Education. 2-56 Binomial Expansion Equation (1 of 2) Represents all of the possibilities for a given set of unordered events n! P pq x n x x! n  x  ! Where P = probability that the unordered outcome will occur n = total number of events x = number of events in one category p = individual probability of x q = individual probability of the other category © McGraw-Hill Education. 2-57 Binomial Expansion Equation (2 of 2) Note : p + q=1  The symbol ! denotes a factorial n! is the product of all integers from n down to 1 4!  4  3  2  1  24 An exception is 0! = 1 Question Two heterozygous brown-eyed (Bb) individuals have five children What is the probability that two of the couple’s five children will have blue eyes? © McGraw-Hill Education. 2-58 Applying the Binomial Expansion Equation (1 of 2) Step 1: Calculate the individual probabilities This can be obtained via a Punnett square Pblue eyes   p  1 4 Pbrown eyes   q  1 4 Step 2: Determine the number of events n = total number of children = 5 x = number of blue-eyed children = 2 Step 3: Substitute the values for p, q, x, and n in the binomial expansion equation © McGraw-Hill Education. 2-59 Applying the Binomial Expansion Equation (2 of 2) n! P p x q n x x! n  x  ! P 5! 1 2! 5  2 ! 4 2    3 4 5 2 P 5 4  3 2 1 1 2  1 3  2  1 ! 16    27 64   0.26 or 26% Therefore 26% of the time, a heterozygous couple’s five children will contain two with blue eyes and three with brown eyes © McGraw-Hill Education. 2-60