Transmission Genetics

2.1: Gregor Mendel Discovered the Basic Principles of Genetic Transmission

  •  Mendel’s Work was not appreciated at first, and he published his findings in 1866, which led to genetics but no one at the time cared

  • The scientists of the day did not understand the significance of Mendel’s experiments

  • In 1900 his work was “rediscovered” and a revolution in biology was launched

    • He died in 1884 without his scientific contributions being acknowledged

  • Gregor Mendel observed phenotypic diversity among pea plants; mainly true-breeding (homozygous phenotypes)

    • True-breeding stays true through generations

  • The Blending Theory of Heredity:

    • Suggested that progeny traits were a MIXTURE of parental characteristics, predicting intermediate traits in offspring

      • Example: black + white cats = gray cat

      • Black and white traits would never reappear if the gray kittens were crossed to each other, meaning that the traits would not go backwards (cannot unmix)

    • Meaning that traits would blend in each generation, but if not, the theory would be disproved

  • Gregor Mendel used controlled mating or “crossing” to perform experimental breeding

    • Controlled crosses between plants: manipulate which plants were bred together, ensuring precise experimental conditions

    • Use of pure-breeding strains: ensured that plants used in experiments were genetically uniform, providing consistent and reliable results

    • Selection of dichotomous traits: two distinct forms making it easier to observe and categorize outcomes

    • Quantification of results: recorded number of offspring exhibiting each trait

    • Use of replicate, reciprocal, and test crosses: confirmed consistency and reliability of experimental results

      • Test crosses: designed to identify the alleles carried by an organism whose genetic makeup is not certain

  • Overall, he proposed a molecular explanation for dominance of the yellow allele over the green allele

    • Yellow is dominant: both alleles present (green and yellow), yellow expressed

    • At least one copy of enzyme can result in a change to yellow (from green)

  • He noticed that F1 hybrid peas did not “breed true”; 25% of F2 plants would produce green seeds, a 3:1 ratio in F2 offspring

    • Green returns after receding for a generation → it’s recessive to yellow

    • F2 offspring with the dominant trait were a mixture of two genotypes (GG and Gg) and plants with the recessive trait were gg (homozygous recessive)

  • Results from Mendel’s seven growing seasons were:

    • 1) dominance of one phenotype over the other in the F1 generation (yellow in this case)

    • 2) reemergence of the recessive phenotype in the F2 generation (gg)

    • 3) a ratio of 3:1 among F2 phenotypes

    • 4) yellow was dominant to green and round was dominant to wrinkled

2.2 Monohybrid Crosses Reveal the Segregation of Alleles

  • Evidence of particulate inheritance and rejection of the blending theory:

    • The observation that all F1 offspring have the same phenotype as one of the pure-breeding parents contradicts the blending theory predicts that the offspring would have a mixture of the two parental phenotypes

      • Also the reemergence of recessive green as it “unmixed the paint”

    • Proposed a new hereditary hypothesis that each trait is determined by two “particles of heredity”, or alleles → particulate inheritance

      • Each plant carries two alleles for each trait

      • Traits must be derived from “discrete factors” or alleles that come from parents and combine in offspring (alleles separate via gamete production)

  • Mendel’s First Law of Equal Segregation:

    • Describes the particulate nature of inheritance and identifies the segregation of alleles during gamete formation and proposes the random union of gametes to produce offspring in predictable proportions

    • Each allele will have an equal probability of ½ of inclusion in a gamete as it receives one copy of each gene

  • Test cross: cross of an organism that has the dominant phenotype to one that has the recessive phenotype to determine whether the dominant organism has the homozygous genotype (GG) or heterozygous genotype (Gg)

    • If plant is homozygous, then all the offspring in the test cross will have the dominant phenotype

    • If plant is heterozygous, then all the offspring in the test cross will have a 1:1 ratio of offspring with dominant phenotype to recessive phenotype

  • Genotypes of F2 offspring:

    • Predicts that F2 plants with dominant phenotype can be either heterozygous or homozygous, BUT those with the dominant phenotype are twice as likely to be heterozygous as homozygous 

2.3 Dihybrid and Trihybrid Cross Reveal the Independent Assortment of Alleles

  • Each of the seven traits Mendel studied showed the same pattern of heredity explained by the law of segregation

    • Each parent has 2 alleles that separate during crossing so each offspring can receive trait from each parent

  • Mendel also studied the inheritance of two or more traits simultaneously leading to Mendel’s law of independent assortment (second law), which is the inheritance of multiple genes

    • To test this, Mendel performed a series of dihybrid crosses, beginning with pure-breeding for the two dominant pea traits 

    • Prediction that F1 are dihybrid, meaning they are heterozygous for the two traits 

    • If the assortment of alleles for each gene is independent, then the gametes produced by F1 plants are equally likely to contain any combination of one allele for seed shape and one for color (RG, Rg, rG, rg), for a frequency of ¼ 

    • A punnett square can then be used to illustrate the F2 generation crossed with the same genotypes as F1 generation

      • Frequency for the punnett square is 1/16 

      • All four phenotypes observed display: both dominant phenotypes, dominant for one phenotype and recessive for the other, and both recessive phenotypes

      • Appear in the ratio of 9:3:3:1

    • The 9:3:3:1 ratios generated in Mendel’s dihybrid crosses illustrate Mendel’s second law of independent assortment

      • States that during gamete formation, the segregation of alleles at one gene is independent of the segregation of alleles at another gene

      • Within the 9:3:3:1 ratio, mendel recognized two for each trait

  • An aid to prediction of gamete frequency:

    • Forked-line (branch tree) diagram: possible because independent assortment means frequency is product of multiple independent events

  • Testing independent assortment by test-cross analysis

    • Mendel predicted that the F1 seeds were dihybrid, of genotype RrGg, and that crossing them to a plant of genotype rrgg would yield four offspring phenotypes with equal frequency (¼)

    • Confirmed that the dihybrid genotype of F1 plant was heterozygous after test crossing with homozygous rrgg, and supported the hypothesis that alleles for one trait assort independently of those from another trait during gamete formation

  • Testing trihybrid cross analysis

    • Crossed a pure-breeding plant (RRGGPP) to another pure breeding plant (rrggpp) → results were (RrGgPp) and these plants are crossed with one another to produce F2

    • In this cross, the # of gamete possibilities is 2n

    • What phase of meiosis accounts for different alleles segregating from each other (disregard crossing over)

      • Meiosis I: Homologous chromosomes pair and separate 

  • Independent Assortment is due to Metaphase I

    • Any alleles are equally likely to get obtained (random chance); different arrangements are likely

2.4 Probability Theory Predicts Mendelian Ratios

  • Mendel recognized that chance is the principle underlying the segregation of alleles for a given gene and the independent assortment of alleles of genes at different loci

    • Four rules of probability theory describe and predict the outcome of genetic events:

      • Product rule

      • Sum rule

      • Conditional probability

      • Binomial probability

  • Product rule

    • If two or more events are independent of one another, their joint probability, the likelihood of their simultaneous or consecutive occurrence is the product of the probabilities of each one individually

      • Also called multiplication rule

      • RrGg → ½ R ; ½ r →RG ¼ ; Rg ¼ ; rG ¼ ; rg ¼ because you have a ½ chance to get a certain allele of R (either dominant or recessive) and ½ chance to get the G (dominant or recessive) 

        • Multiply the two together to get ¼ probability

  • Sum rule

    • It calculates the joint probability of occurrence of any set of two or more outcomes when the possible outcomes are mutually exclusive events

    • The individual probabilities are summed; this is used when more than one outcome will satisfy the conditions of the probability question

      • Also called the sum rule

      • Probability that an F2 offspring having two dominant phenotypes (RrGg) is obtained by applying the sum rule of RRGG 1/16 + RrGG 2/16 + RRGg 2/16 + RrGg 4/16 = 9/16

  • Conditional Probability

    • The product and sum rules are used before a cross is made, in order to predict the likelihood of certain outcomes

    • Involves questions asked after a cross has been made and is applied when information about the outcome modifies the probability calculation

      • Example: for cross Gg x Gg, what is the probability that the yellow-seeded progeny are heterozygous?

      • Yellow seeded offspring makeup ¾ of the offspring with two possible genotypes: GG and Gg

        • Because there cannot be gg for a yellow-seeded offspring, there is a ⅔ chance they are Gg and a ⅓ chance they are GG

        • Only focusing on what is asked (yellow)

  • Binomial Probability

    • Some questions involve predicting the likelihood of a series of events (two or more possible outcomes each time)

    • Use binomial probability calculations to answer this type of question

    • Expands the binomial expression to reflect the number of outcome combinations and probability of each

    • Construction of a binomial expansion formula

      • A binomial expansion contains two variables:

        • p, the frequency of one outcome

        • q, frequency of the alternative outcome 

        • (p + q)= 1, since there are only two outcomes 

        • n = number of successive events (p + q)^n

    • Application of binomial expansion to progeny phenotypes

      • In a self-fertilized Gg pea plant, give the proportion of yellow and green peas in pods with six peas each: 

      • A shortcut to the binomial expansion is Pascal’s triangle

      • The binomial coefficients are used to multiply the binomial probability of each outcome class

        • For example, to get all yellow peas it would be set up like: 1(p^6) = (¾)^6 = 0.178 since p = ¾ (probability to get boys)

        • Then for the probability to get three yellow and three green would be 20(p^3)(q^3) = 20(¾ ^3)(¾ ^3)= 0.132

        • The sum would be 1.00

2.5 Chi-Square Analysis Tests the Fit between Observed Values and Expected Outcomes

  • Quantifies how closely an experimental observation matches the expected outcome by determining the probability of the observed outcome

    • Smaller p value = more confident that anaylsis is correct

    • Lower than chi-square = fail to reject ; accurate data 

    • Larger than chi square = reject; not very accurate 

    • Use d= n-1

  • Find expected: (total)(probability of what was meant to be expected)

    • Ex: total of 7324 but I am expecting that 75% of the F2 would be round 

      • (7324)(75%)= 5493 round seeds as expected

    • For a trihybrid cross, ratios consist of 27:9:9:9:3:3:3:1

2.6 Autosomal Inheritance and Molecular Genetics Parallel the Predictions of Mendel’s Hereditary Principles

  • Autosomal inheritance: refers to transmission of genes carried on autosomes (non-sex chromosomes) found in both males and females

    • There are two copies of each autosome in a diploid organism, one from the mother and one from the father 

    • In humans, there are 22 pairs of autosomes

    • The 23rd are the sex chromosomes designated x and y

  • Assisted with the construction of pedigrees

  • Autosomal Dominant Inheritance

    • Autosomal dominant inheritance has six characteristics:

      • 1. Males and females have the trait in equal frequency; should not have 1 sex displaying a trait more

      • 2. Each individual who has the trait has at least one parent with the trait →ONE must have it

      • 3. Either sex can transmit the trait to a child

      • 4. If neither parent has the trait, none of their children will have it

      • 5. And if the trait is rare… those with the trait are likely heterozygous and in crosses where one parent has the trait and the other does not, half offspring will have the trait

      • 6. And both parents have it, they may produce children who do not have it (parents are likely heterozygous) 

  • Autosomal Recessive Inheritance

    • Has five key features:

      • 1. Males and females have the trait in equal frequency 

      • 2. Individuals who have the trait are often born to parents who do not (parents are heterozygous)

      • 3. If both parents have the trait, all children will have it (100%)

      • 4. The trait is not usually seen in each generation, rather it is typically seen among siblings

      • 5. If only one parent has the trait, a child can only have the trait if the other parent is heterozygous 

  • If the gene causing white eyes is autosomal, and a true-breeding white fly is crossed, what do you expect in the F1 generation? 

    • 100% red is what is assumed BUT

    • Sex-linked traits say otherwise

    • The gene is only on the X chromosome, so XY individuals have HALF the number of alleles and are HEMIZYGOUS

      • This is because males and females in this case inherent traits in different matters

      • When there are different ratios, it implies that we are looking at genes that are sex-linked on the x chromosome

  • X- linked recessive

    • 1. Unaffected females with affected sons/fathers

    • 2. More affected males than females

      • Bc there is only 1 X chromosomes, females can mask the trait as they have another X chromosome

      • For males, because they only have 1 X chromosome, it makes them display it more

    • Example of this is Hemophilia in European Royalty

  • X-linked dominant

    • 1. Affected males with 100% of daughters affected because only daughters will get the x^A

      • Males won’t get it as they have a Y

  • Y linked

    • Affected male has 100% male offspring with the trait because this is exclusively males

      • ALL sons MUST have it because of the Y chromosome goes to ALL males

  • Some important genes are located on small mitochondrial nucleoids (mitochondrial chromosome)

    • Can inherit DNA from organelles

  • Organelles inherited through cytoplasm of mother (Organellar inheritance)

    • Exclusively material, that is so small and delivers nucleus 

    • All DNA in organelles is material origin

    • Mitochondrial just like plants

    • Look for:

      • 1. If mother affected, 100% of children will be affected

      • 2. If only father affected, 0% of children affected