Autosomal Heredity PDF - BMS 532 Lecture 5

Autosomal Heredity CLASSIC MENDELIAN GENETICS, PROBABILITIES, AND LINKED GENES ON AUTOSOMES BMS 532 B LO C K 2 L E C T U R E 5  Objectives This section may be mostly review; however, we are going to take a slightly different approach by focusing on chromosomes and their behavior in inheritanc...

Autosomal Heredity CLASSIC MENDELIAN GENETICS, PROBABILITIES, AND LINKED GENES ON AUTOSOMES BMS 532 B LO C K 2 L E C T U R E 5  Objectives This section may be mostly review; however, we are going to take a slightly different approach by focusing on chromosomes and their behavior in inheritance. It will enable us to expand our thinking to include gene linkage. 1. Define the following terms: Allele, Locus, Genotype, Phenotype, True-breeding, Heterozygote, Homozygote, Parental, Filial 1, Filial 2, Dominant, Recessive, Monohybrid Cross, Dihybrid Cross, Back/Test cross, Mendelian Inheritance, Nonmendelian Inheritance, linked genes, addition rule, and multiplication rule 2. Determine the expected gamete outcomes following meiosis 3. Determine the expected phenotypes and genotypes of a given cross ◦ Outline an example of Mendel’s monohybrid crosses, the results obtained and what they indicated. ◦ Outline an example of Mendel’s dihybrid crosses, the results obtained and what they indicated. ◦ Diagram and explain why a dihybrid cross yields a 9:3:3:1 ratio ◦ Explain a testcross and the importance of including recessive parental genotypes in the cross 4. Assess the consequences for genotype and phenotype with parental and recombinant chromosomes with consideration of cis and trans arrangements (continued from packet 1) 5. Calculate probabilities for a given scenario with emphasis on phenotypic outcomes ◦ Differentiate between and give examples of the application of both the addition and multiplication rules ◦ Apply these rules as appropriate for specific scenarios to define whether the organism will be phenotypically dominant or recessive ◦ Understand the application of the binomial equation (we will NOT perform calculations requiring this) LO1 Terminology Other ways to look at the terms… Updated Definition of GENE ◦ The unit of heredity made of DNA or RNA that encodes a coherent set of potentially overlapping functional product molecules (RNA or Protein) that influences phenotype ◦ Measuring or evaluating the influence on phenotype may not be possible with current technology Allele = variations or variants of a gene Locus = the specific position of a gene on a chromosome Heterozygous = containing more than one type of allele for a given gene Homozygous = containing only one type of allele for a given gene LO1 What are these Genes causing? Characters ◦ The general characteristics of an organism ◦ Petal Color = a character Trait/Variant ◦ The specific properties of a character ◦ White Petals = a variant of petal color TRUE-BREEDING Strain/Line ◦ A version that continues to produce the same trait after several generations of self- fertilization LO1 Gregor Mendel A.K.A. Father of Modern Genetics or The Pea Plant Guy Examined inheritance of easily visible traits in pea plants (1856- 1863) ◦Pod color, seed type, flower color, etc… PARTICULATE THEORY of heredity ◦Units of heredity are PARTICLES that occur in pairs ◦Those pairs segregate from one another during the formation of gametes ◦ MEIOSIS I LO1, LO3 Crosses and Mendel’s Experimental Design Single Factor Cross (Monohybrid cross) ◦ Observation of a single character ◦ Requires more than one VARIANT Monohybrids ◦ Single character hybrids produced from a cross between 2 parents with different variants Experimental Design ◦ TRUE BREEDING PLANTS ◦ Parental (P) ◦ Offspring from P x P ◦ Filial Generation (F1) ◦ Self-Fertilization of F1 ◦ 2nd Filial Generation (F2) LO1, LO2, LO3 Generational Analysis Defining dominance (which trait is observed phenotypically when 2 versions of the gene conferring the trait are present) requires multiple experiments and analysis of multiple generations Dominant = version of gene that is observed phenotypically in the heterozygous state Recessive = version of gene that is typically only observed phenotypically in the homozygous state Any trait can be designated with random letters to indicate which version of the trait (allele) you think is going to be dominant ◦ Evaluation of the phenotypes of the offspring over several generations will confirm that dominance ◦ Capital letters (A,B,C, etc…) = dominant ◦ Lower case letters (a,b,c, etc…) = recessive LO1, LO2, LO3 Mendelian Inheritance Observation of traits in offspring that matches expectations based on Mendel’s rules/principles Mendel’s Principles (Laws) ◦ Principle of Segregation ◦ Diploids have 2 alleles for a given character (one paternal and one maternal) ◦ These alleles separate in the formation of gametes giving equal probability of passing on either in the gametes ◦ Modern Version: Homologous Chromosomes Segregate/Separate ◦ Principle of Independent Assortment ◦ Genes for different characteristics located on different loci assort independently ◦ Modern Version: Unlinked genes (genes on separate chromosomes) assort independently of one another LO1, LO2, LO3 G G gg Law of Segregation In the production of gametes ◦ Two copies of the same gene separate ◦ Each gamete only receives 1 copy ◦ HOMOLOGOUS CHROMOSOMES separate during meiosis G G gg LO1, LO2, LO3 Law of Independent Assortment Forms of different genes assort independently of one another during gamete formation ◦Forms of genes = alleles Dihybrid cross = cross evaluating 2 traits Limitations ◦ONLY applies to genes on SEPARATE chromosomes ◦Genes in close proximity on the same chromosome do NOT sort independently (linked genes) LO1, LO2, LO3 Hypotheses and Observation Phenotype is what we can physically observe T T Punnett Squares ◦ Allow for a quick and easy determination of the outcomes of crosses ◦ Defines what the likelihood of obtaining a particular outcome is Punnett squares are HYPOTHESES for the genotypes and expected corresponding phenotypes of a given cross ◦ WITHOUT EXPERIMENTATION (i.e. gene sequencing) THERE IS NO WAY TO DETERMINE DEFINITIVELY A t Tt Tt GENOTYPE If you think of Punnett squares as a hypothesis of what you think will happen, then you can reduce even the most complicated gene combinations to a basic math problem t Tt Tt T = tall t = short plant LO1, LO2, LO3 Confirming Inheritance: Backcross or Testcross Heterozygote vs homozygote TY Ty tY ty recessive In a dihybrid cross, heterozygotes TtY Tty ttY tty for two traits are crossed to ty homozygotes that are recessive for y y y y both traits TtY Tty ttY tty ◦ TtYy X ttyy ty This type of cross is particularly y y y y useful for demonstrating the law of TtY Tty ttY tty independent assortment ty y y y y Enables visualization of all potential phenotypes for the traits being TtY Tty ttY tty evaluated ty y y y y T = tall t = short Y = yellow y = green LO1, LO2, LO3 Autosomal Inheritance of Linked Genes This is the first Nonmendelian Inheritance pattern observed Linked genes are genes located on the same chromosome Linked genes will be inherited together more frequently than unlinked genes thus they will most likely NOT follow independent assortment Recombination enables these genes to be observed differently than in the parental generations (recombinant offspring) Genes can be linked in cis (dominant forms together) or in trans (dominant form is with recessive form of other gene) LO1, LO4 Recombination: Parentals vs Recombinants Gene linkage adds to the complexity of TY Ty tY ty outcomes particularly for humans The backcross or testcross can be used to TtY Tty ttY tty reveal recombination and map ty chromosomes/gene locations y y y y Parental chromosomes differ from recombinant TtY Tty ttY tty chromosomes in literal gene content ty y y y y Inheritance of a recombinant chromosome provides additional variation from the parental TtY Tty ttY tty phenotypes as new combinations of genes ty become possible y y y y Although all the same gametes are possible TtY Tty ttY tty always, the ratios will change ty y y y y T = tall t = short Y = yellow y = green LO4 G G gg Gene Linkage RR rr In the production of gametes ◦ Linked genes are more likely to segregate together ◦ In the absence of recombination, they WILL be together ◦ This will cause a specific set of phenotypes to be more common GG = dominant Grainy texture gg = recessive smooth texture RR = dominant round shape G G gg rr = recessive distorted shape Due to gene linkage, phenotypes expected are: RR rr ◦ grainy round AND smooth distorted Only recombination can produce the following phenotypes: ◦ Grainy distorted AND smooth round LO1, LO4 Recombination: Parentals vs Recombinants When looking at gene linkage, we much consider the phenotypes from TWO traits TY Ty tY ty ◦ Represents the only way to determine whether recombination occurred ◦ See separation from vs. inheritance with TtY Tty ttY tty ty ◦ Same gametes are possible but outcomes will not be equal y y y y A heterozygote can still make TY, Ty, tY, and ty TtY Tty ttY tty ty HOWEVER: y y y y ◦ If TY and ty are parentals ◦ majority of offspring will be TtYy and ttyy (tall yellow vs. short TtY Tty ttY tty green) ty ◦ Far fewer will be Ttyy and ttYy (tall green vs. short yellow) y y y y ◦ If Ty and tY are parentals ◦ Majority of offspring will be Ttyy and ttYy (tall green vs. short TtY Tty ttY tty yellow) ty ◦ Far fewer will be TtYy and ttyy (tall yellow vs. short green) y y y y T = tall t = short Y = yellow y = green LO1, Probability and Statistics: LO5 Using Math to Understand Genetics Number of Times a Particular Outcome Occurs Probability = Total Number of Possible Outcomes Predict the likelihood of having an affected child The chance that a cross between 2 individuals will produce a particular outcome Accuracy depends on size of the sample Random Sampling Error ◦ Deviation between observed and expected Independent Outcomes ◦ Outcome of one does not affect the probability of another LO1, LO5 Probability Rules Addition Rule: ◦The probability of obtaining one or the other of two mutually exclusive events is the sum of their individual probabilities Multiplication Rule: ◦The probability of two independent events occurring simultaneously equals the product of their individual probabilities You have actually been doing this for years. We are simply naming the rules and discussing how they work in Genetics analysis. LO1, LO5 Addition Rule The probability of two or more mutually exclusive events is determined by adding the probability of each event. What is the probability of rolling either a 3 or a 4 on a single role of the die? Each roll is an independent event with equal chances of getting a particular number Each independent probability is therefore 1/6 so we add the independent probabilities together. 1/6 + 1/6 = 2/6 or 1/3. 1 9 LO1, LO5 Multiplication Rule The probability of two or more independent events taking place together is determined by multiplying their individual probabilities together. Rolling of a die illustrates this principle very well. The probability of rolling a 4 on a single role of a die is 1/6. What about the probability of rolling consecutive 4s on two roles of the die? ◦ This is the bringing together the probabilities of 2 separate and independent events ◦ Multiplication rule says to multiply the independent probabilities together. ◦ 1/6 x 1/6 = 1/36 20 LO1, LO5 When to use each rule… Good rule of thumb to use when determining which rule is preferable: ◦ AND versus OR ◦ AND = multiplication rule OR = addition rule If only one option of 2 is possible in a given question = OR If multiple events that are independent or combine repeated events = AND What is the chance that a male and then a female will be born? ◦ Male vs female = OR = addition rule 1 out of 2 ◦ First a male then a female = AND = multiplication rule of the 2 individual probabilties LO1, LO5 Addition Rule The probability of obtaining one or the other of 2 mutually exclusive events, A or B, is the sum of the separate probabilities Probability of WW or Ww = Probability of WW + Probability of Ww Every time you use a punnet square and say the probabilities of getting particular phenotypes, you are using the ADDITION RULE! LO1, LO5 Product Rule The probability that two or more What is the probability that a independent outcomes will occur is couple’s first 3 children will exhibit a equal to the product of their recessive trait if both parents are individual probabilities heterozygotes? Aa X Aa Use Punnett Squares! What is the probability of aa? Then what is the probability of aa 1. Calculate the individual happening 3 times? probabilities ◦ Probability 1 x 2 x 3 2. Multiply the individual probabilities LO1, LO5 Product Rule Can be used to predict the outcome of a cross involving two or more genes AaBbCC X AabbCc What is the probability that the offspring will be AAbbCc? Probability of AA? Probability of bb? Probability of Cc? P = pAA x pbb x pCc LO1, LO5 More Complex Probabilities X Consider Mendel’s cross of two heterozygous tall plants. What is the likelihood of having three offspring where two are normal height and one is short? This is more difficult because there are multiple ways this could occur with three offspring. Tall could be TT or Tt = 1/4 + 1/2 = 3/4 or Short must be 1/4. Each grouping is 3/4 x 3/4 x 1/4 = 9/64. 9/64 + 9/64 + 9/64 = 27/64. This can become or tedious. 25  Data Analysis LO1, LO5 Genetic data analysis makes use of probability and statistics Offspring from crosses are predicted using binomial probability In a binomial experiment there are two mutually exclusive outcomes, often referred to as "success" and "failure". Example: Flipping a coin where ◦ heads = success and ◦ tails = failure If the probability of success is p, the probability of failure is 1 - p.; In binomial trials the rate of success is constant (0.5) If the probability of possibility A is p and the probability of the alternative possibility B is q, then the probability that, in n trials, A is realized s times and B is realized t times is n! s t n! OR Probability = pxqn-x s!t! p q x! (n-x)! EXAMPLE TIME MOVING FROM PUNNETT SQUARES TO CHROMOSOME ANALYSIS You hypothesize that an allele is autosomal dominant to another allele. 1 genes with 2 variants that must have distinct phenotypes to evaluate What designation should be used? What are the expected outcomes? What additional experimentation needs to be done to further support your hypothesis? Punnett Squares You hypothesize that 2 genes are UNLINKED with two variants for each gene available. 2 genes with 2 variants must have distinct phenotypes to evaluate What designation should be used? What are the best choices for evaluating the traits and their inheritance? Punnett Squares K and L are designating 2 different genes. There are 2 alleles for each of these genes. What are the potential genotypes for these 2 genes and their 2 alleles? What are the potential gametes if the genes are unlinked? What are the potential gametes if the genes are linked in cis without recombination? With recombination? What are the potential gametes if the genes are linked in trans without recombination? With recombination? Hypothesized Genotype: AaBb on one chromosome (in cis) EeGg on another chromosome (in cis) Draw example chromosomes How would these be inherited in the absence of recombination? How would these be inherited if recombination occurred between A and B? Between E and G? Between both simultaneously?