Ch 3 Simple Mendelian Inheritance PDF

Because learning changes everything. ® Chapter 3 Mendelian Inheritance © < add the year> McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw...

Because learning changes everything. ® Chapter 3 Mendelian Inheritance © < add the year> McGraw Hill. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill.  Topics What was Gregor Mendel’s work with pea plants? What are the laws of segregation and independent assortment? What is the chromosomal theory of inheritance? What are common inheritance patterns in humans? How do we use Punnett squares for 1- and 2-factor crosses? What is a genetic pedigree? How do we predict probable genetic outcomes and how do we know if results are statistically significant? © McGraw Hill 2  Mendel’s Study of Pea Plants Gregor Johann Mendel (1822 to 1884) - father of genetics From 1856 to 1864, he performed thousands of crosses Used the garden pea (Pisum sativum) to study the natural laws governing plants hybrids His work, entitled “Experiments on Plant Hybrids” was published in 1866 → Ignored for 34 years! In 1900, Mendel’s work was rediscovered © McGraw Hill 3  Mendel Chose Pea Plants as His Experimental Organism Mendel carried out two types of breeding experiments 1. Self-fertilization Pollen and egg are derived from the same plant Occurs naturally in peas 2. Cross-fertilization Pollen and egg are derived from two different plants Required removing and manipulating anthers If two parent plants differ in a particular trait, this produces hybrids → a hybridization experiment © McGraw Hill 4  Cross-Fertilization How Mendel cross-fertilized pea plants © McGraw Hill 5  Mendel Studied Seven Characters that Bred True Characters = observable characteristics Trait or variant = specific properties of a character A variety that produces the same trait over several generations is termed a true-breeder Eye color is a character Blue eyes is a trait or variant © McGraw Hill 6  Mendel studied 7 characters Access the text alternative for slide images. © McGraw Hill 7  Single Factor Crosses 1. P (parental) cross - two plants that differ in regard to only one character 2. Product = F1 generation seeds → grow into plants of the F1 generation. 3. F1 generation plants self- fertilize → produce seeds that are F2 generation → grow into F2 generation plants. Access the text alternative for slide images. © McGraw Hill 8  Data from Single-factor Crosses P Cross F1 generation F2 generation Ratio Tall × dwarf stem All tall 787 tall, 277 dwarf 2.84:1 Round × wrinkled 5,474 round, 1,850 All round 2.96:1 seeds wrinkled 6,022 yellow, 2,001 Yellow × Green seeds All yellow 3.01:1 green Purple × white flowers All purple 705 purple, 224 white 3.15:1 Axial × terminal All axial 651 axial, 207 terminal 3.14:1 flowers Smooth × constricted 882 smooth, 229 All smooth 2.95:1 pods constricted Green × yellow pods All green 428 green, 152 yellow 2.82:1 © McGraw Hill 9  Interpreting the Data Mendel’s proposed three ideas: 1. Traits do not blend together to produce offspring of intermediate height. One variant is dominant and its effect can be seen The other variant is recessive and is not seen in the F1 offspring 2. Particulate theory of inheritance: genetic determinants that govern traits are inherited as discrete units that remain unchanged as they are passed from parent to offspring. Discrete units = “genes” 3. Law of Segregation © McGraw Hill 10  Law of Segregation The two copies of a gene segregate (or separate) from each other during the process that gives rise to gametes. Each gamete carries one copy of a given gene. A gamete carries a single allele of a given gene. https://www.expii.com/t/law-of-segregation-definition-role-10972 © McGraw Hill 11  Law of Segregation Related terms: Mendelian unit factors → now called genes Alleles = different versions of the same gene An individual with two identical alleles = homozygous An individual with two different alleles = heterozygous Genotype = the specific allelic composition of an individual Phenotype = the observable traits of an individual © McGraw Hill 12  Punnett Squares Used to predict the outcome of simple genetic crosses It was proposed by the English geneticist, Reginald Punnett The Punnett square approach can be used to examine the cross of heterozygous tall plants TT Tt (Tt x Tt) Genotypic ratio Tt tt 1:2:1 Phenotypic ratio 3 :1 © McGraw Hill 13  Two-Factor Crosses Crossing individual plants that differ in two characters For example Character 1 = Seed texture (round versus wrinkled) Character 2 = Seed color (yellow versus green) There are two possible patterns of inheritance for these characters Linked assortment Independent assortment © McGraw Hill 14  Linked Assortment (a) HYPOTHESIS: Linked assortment © McGraw Hill 15  Independent Assortment (b) HYPOTHESIS: Independent assortment © McGraw Hill 16 Mendel's Analysis of Two Factor Crosses Figure 2.8 Access the text alternative for slide images. © McGraw Hill 17  Data from Two-Factor Crosses P Cross F1 generation F2 generation Round, Yellow seeds X All round, yellow 315 round, yellow seeds wrinkled, green seeds 101 wrinkled, yellow seeds 108 round, green seeds 32 green, wrinkled seeds RRYY x rryy All RrYy © McGraw Hill 18  Two Factor Cross: Interpreting the Data The F2 generation contains nonparentals (combinations not found in the parentals) Round and Green Wrinkled and Yellow Contradicts the linked assortment model © McGraw Hill 19  Two Factor Cross: Interpreting the Data If the genes assort independently Predicted phenotypic ratio in the F2 generation - 9:3:3:1 Mendel’s data were very close to segregation expectations Thus, he proposed the law of Independent Assortment: Two different genes will randomly assort their genes during the process that gives rise to gametes. Parent = RrYy, the R and r alleles will segregate into gametes independently of the Y and y alleles. RY Ry 4 types of rY gametes made in ry equal amounts © McGraw Hill 20  Independent Assortment Access the text alternative for slide images. © McGraw Hill 21  Two Factor Cross: Interpreting the Data P Cross F1 generation F2 generation Ratio Round, All round, yellow 315 round, yellow seeds 9.8 Yellow seeds X wrinkled, green seeds Blank Blank 101 wrinkled, yellow seeds 3.2 Blank Blank 108 round, green seeds 3.4 Blank Blank 32 green, wrinkled seeds 1.0 © McGraw Hill 22  Mendel's Law of Independent Assortment Some genes are linked because they are close together on the same chromosome Genetic recombination – when an offspring receives a combination of alleles that differs from the parental generation Can be due to: Independent assortment Crossing over (Chapter 6) © McGraw Hill 23  Punnett Square for a Two-factor Cross Access the text alternative for slide images. © McGraw Hill 24  Punnett Squares – 3 or more genes In crosses involving three or more independently assorting genes The Punnett square becomes too cumbersome 64 squares for three genes! More reasonable alternatives are the forked-line method or the multiplication method © McGraw Hill 25  3-Factor Cross Probability of dwarf, wrinkled green Probability of tall, round, yellow offspring? offspring? Multiply ¼ x ¼ x ¼ = 1/64 Multiply ¾ x ¾ x ¾ = 27/64 Access the text alternative for slide images. © McGraw Hill 26  Modern Genetics The defective copies of genes are termed loss-of-function alleles Unknowingly, Mendel had used seven loss-of-function alleles in his studies on pea plants Loss-of-function alleles are commonly inherited in a recessive manner © McGraw Hill 27  The Chromosome Theory of Inheritance The chromosome theory of inheritance describes how the transmission of chromosomes account for Mendelian patterns of inheritance Established how chromosomes carry and transmit genetic determinants of traits https://en.m.wikipedia.org/wiki/File:Human_chromosome_12_from_Gene_Gateway_-_with_label.png https://en.m.wikipedia.org/wiki/File:Human_chromosome_12_from_Gene_Gateway_ -_with_label.png © McGraw Hill 28 Chromosome Theory of Inheritance - Fundamental Principles 1. Chromosomes contain the genetic material 2. Chromosomes are replicated and passed from parent to offspring 3. The nuclei of most eukaryotic cells contain chromosomes that are found in homologous pairs, they are diploid 4. During meiosis, each homolog segregates into one of the two daughter nuclei; during the formation of gametes, different types of (nonhomologous) chromosomes segregate independently 5. Each parent contributes one set of chromosomes to its offspring The sets are functionally equivalent; each carries a full complement of genes © McGraw Hill 29  The Separation of Homologs During Meiosis Explains the Law of Segregation Homologous chromosomes segregate from each other in meiosis 1. This leads to the segregation of the alleles into separate gametes. Access the text alternative for slide images. © McGraw Hill 30  The Random Alignment of Homologs During Meiosis Explains the Law of Independent Assortment Access the text alternative for slide images. © McGraw Hill 31  Pedigree Analysis Pedigree analysis: used to determine the pattern of inheritance of traits in humans (b) Symbols used in a human pedigree © McGraw Hill 32  Pedigree Analysis Used to determine the inheritance pattern of human genetic diseases Genes that play a role in disease may exist as A non-disease-causing allele that encodes a functionally normal protein A mutant allele that causes disease symptoms Diseases that follow a simple Mendelian pattern of inheritance can be Dominant Recessive © McGraw Hill 33  Pedigree Analysis Recessive pattern of inheritance Two unaffected heterozygous individuals →25% of their offspring affected Two affected individuals →100% affected offspring Dominant pattern of inheritance An affected individual will have inherited the gene from at least one affected parent OR, a new mutation that occurred during gamete formation © McGraw Hill 34  Human Pedigree Showing Cystic Fibrosis The gene encodes a protein called the cystic fibrosis transmembrane conductance regulator (CFTR) regulates ion transport across the cell membrane The mutant allele creates an altered CFTR protein that ultimately causes ion imbalance abnormalities in the pancreas, intestine, Figure 2.12a sweat glands and lungs (a) Human pedigree for cystic fibrosis (autosomal recessive) Access the text alternative for slide images. © McGraw Hill 35  Probability 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 36  Probability 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 vs 1000 times Not unusual - 70% heads and 30% tails vs closer to 50% and 50% © McGraw Hill 37  Probability 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 38  Product Rule 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 39  Product Rule Autosomal recessive disease - congenital analgesia Extreme sensations are not perceived as painful Two alleles P = Non-disease-causing allele p = Recessive allele that causes congenital analgesia 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 40  Applying the Product Rule Step 1: Calculate the individual probabilities This can be obtained via a Punnett square The cross is Pp x Pp Ratio from a Punnett square is 1 PP : 2 Pp : 1 pp Step 2: Multiply the individual probabilities 1/4 × 1/4 × 1/4 = 1/64 1/64 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 41  Binomial Expansion Equation Represents all of the possibilities for a given set of unordered events n! P= p x q 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 42  Binomial Expansion Equation 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 43  Applying the Binomial Expansion Equation 1 Step 1: Calculate the individual probabilities This can be obtained via a Punnett square The cross is Bb x Bb; B (brown) is dominant to b (blue) P(blue) = ¼ P(brown) = ¾ 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 44  Applying the Binomial Expansion Equation 2 P = probability that the unordered outcome will occur n = total number of events (5 children) n! x = number of events in one category (2 with blue eyes) P= p x q n −x p = individual probability of x (1/4) x!( n − x ) ! q = individual probability of the other category (3/4) ( ) (34) 5! 2 5− 2 P= 1 2!( 5 − 2 ) ! 4 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 45  The Chi Square Test A statistical method used to determine goodness of fit Goodness of fit refers to how close the observed data are to those predicted from a hypothesis Note: The chi square test does not prove that a hypothesis is correct It evaluates whether or not the data and the hypothesis have a good fit Used to reject Null hypothesis! © McGraw Hill 46  P Value Probability that the deviation between observed and expected values are due to random chance Used to make conclusion about statistical significance Example: Coin flip 20x 16 heads / 4 tails Is coin unfair? Mathematical calculation – 1.18% probability due to random chance P value < 0.05 (due to random chance < 5% of time) © McGraw Hill 47  The Chi Square Test The general formula is x =  (O − E) E 2 2 where O = observed data in each category E = expected data in each category based on the experimenter’s hypothesis ∑ = Sum of the calculations for each category © McGraw Hill 48  Chi Square Table Chi Square Values and Probability Degrees of Null Hypothesis Null Hypothesis P 0.99 0.95 0.80 0.50 0.20 Freedom Rejected 0.05 Rejected 0.01 1 0.000157 0.00393 0.0642 0.455 1.642 3.841 6.635 2 0.020 0.103 0.446 1.386 3.219 5.991 9.210 3 0.115 0.352 1.005 2.366 4.642 7.815 11.345 4 0.297 0.711 1.649 3.357 5.989 9.488 13.277 5 0.554 1.145 2.343 4.351 7.289 11.070 15.086 6 0.872 1.635 3.070 5.348 8.558 12.592 16.812 7 1.239 2.167 3.822 6.346 9.803 14.067 18.475 8 1.646 2.733 4.594 7.344 11.030 15.507 20.090 9 2.088 3.325 5.380 8.343 12.242 16.919 21.666 10 2.558 3.940 6.179 9.342 13.442 18.307 23.209 15 5.229 7.261 10.307 14.339 19.311 24.996 30.578 20 8.260 10.851 14.578 19.337 25.038 31.410 37.566 25 11.524 14.611 18.940 24.337 30.675 37.652 44.314 30 14.953 18.493 23.364 29.336 36.250 43.773 50.892 Source: Fisher, R. A., and Yates, F. (1943) Statistical Tables for Biological, Agricultural, and Medical Research. Oliver and Boyd, London. © McGraw Hill 49  Ch 3 Study Guide Summarize Gregor Mendel’s work with pea plants and describe his contribution to the field of genetics Law of segregation Law of independent assortment Predict the outcome of single-factor and two-factor crosses using Punnett squares Differentiate P, F1, and F2 generations Define loss-of-function allele List the key tenets of the chromosomal theory of inheritance Recognize features of a pedigree Evaluate a pedigree to determine if a trait or disease is dominant or recessive Predict genetic outcomes using the product rule of probability Evaluate the validity of a hypothesis using a Chi-square © McGraw Hill 50