L12 - Heredity

Genetics – Current News

  • Many resources and programs related to genetics in the USA are being cut unpredictably and suddenly.

  • These cuts have negative effects on global health and progress in genetics research.

Lecture 11 – Basic Principles of Heredity (Mendelian Genetics)

Learning Objectives

  1. Explain key principles of heredity initially discovered by Gregor Mendel, including:

    • Genetic information is passed from parents to offspring via genes.

    • The two alleles at each locus in the parent separate randomly during gamete formation (segregation).

    • Genetic information from parents combines in offspring.

    • Some alleles are 'dominant' or 'recessive' to others (concept of dominance).

    • Alleles at different loci are transmitted independently if they are on different chromosomes or unlinked on the same chromosome; this involves the random separation of homologous chromosomes, addressed using dihybrid crosses.

  2. Use principles of heredity to predict the proportion of progeny with a given genotype and phenotype for a particular genetic cross in two different ways:

    • Using Punnett squares

    • Applying probabilities

    • Make predictions for:
      a. Monohybrid crosses
      b. Dihybrid crosses

Mendel's Findings

Monohybrid Crosses

  1. Offspring receive genetic information from both parents.

  2. Principle of Segregation (alleles at one locus):

    • An individual has two separate alleles at a given locus.

    • These alleles separate during gamete formation.

    • They separate in equal proportions.

  3. Principle of Independent Assortment (genes at different loci):

    • Alleles at different loci separate independently if unlinked.

    • Crossing over can occur during anaphase II.

  4. One allele can be ‘dominant’ to another.

Dominance and Recessivity

Example 1: Recessive Mutation

  • Wild type allele (+) is dominant to mutant allele (m).

  • No functional protein is produced by the mutant allele.

  • Sufficient protein is produced by the wild type allele.

  • Mutation displays a recessive pattern of inheritance where only individuals with two 'm' alleles exhibit the disease (e.g., Phenylketonuria - PKU).

  • Definition of haplosufficient: An allele that can produce enough functional protein with just one copy.

Example 2: Dominant Mutation

  • This mutation shows a dominant pattern of inheritance where individuals with a single 'M' allele exhibit the disease.

  • Mechanisms of dominance can include:

    • Haploinsufficiency: A single wild type (+) allele does not produce enough protein.

    • Dominant Negative Mutation: Mutant polypeptides distort protein function and can interfere with the function of normal proteins.

Cellular Mechanisms in Mendelian Traits

  • SBEI Gene: Highly expressed in chloroplasts/amyloplasts during early seed development and catalyzes a reaction in the starch biosynthesis pathway (Smith, 1988; Edwards et al., 1988).

  • The wild-type round seed allele is dominant over the wrinkled allele due to genetic variation influencing phenotype.

    • A transposable element insertion in the wild-type starch branching enzyme SBEI allele increases starch and lipid content, which leads to a wrinkled phenotype due to water entering the seed through osmosis (Bhattacharyya et al., 1990; 1993).

Predicting Outcomes of Genetic Crosses

Methods

  1. Punnett Squares

  2. Probability

    • Key principle of segregation: Two alleles at a locus segregate independently and with equal probability into gametes.

    • Must know which allele is dominant/recessive to predict phenotypes.

Examples of Genetic Cross Prediction

  • Crossing two pea plants, one tall (TT) and one short (tt) where T is completely dominant to t.

  • Proportion of offspring that are short:

    • a. 0 (none)

    • b. ¼

    • c. 1/3

    • d. ½

    • e. 1 (all)

Genetic Ratios

Phenotypic Ratios for Simple Genetic Crosses


  • With complete dominance:

    Genotypes of Parents

    Phenotypic Ratio of Progeny

    Genotypes of Progeny


    Aa × Aa

    3:1

    3/4 A_ : 1/4 aa


    Aa × aa

    1:1

    1/2 Aa : 1/2 aa


    AA × AA

    Uniform - All showing A

    All AA


    aa × aa

    Uniform - All showing a

    All aa


    AA × aa

    Uniform - All showing A

    All Aa


    AA × Aa

    All AA

    All Aa

    Genotypic Ratios for Simple Genetic Crosses

    Genotypes of Parents

    Genotypic Ratio of Progeny

    Genotypes of Progeny

    Aa × Aa

    1:2:1

    1/4 AA : 1/2 Aa : 1/4 aa

    Aa × aa

    1:1

    1/2 Aa : 1/2 aa

    AA × AA

    Uniform - All AA

    All AA

    aa × aa

    Uniform - All aa

    All aa

    AA × aa

    Uniform - All Aa

    All Aa

    Probability Principles

    Definitions

    • Probability: "the likelihood of the occurrence of a particular event" (Pierce, 2021).

    • Example: Likelihood of tossing a coin and getting ‘heads’ three times.

    • To predict outcomes using probability: Need large data sets or knowledge of frequency of events occurring.

    • For genetic crosses, alleles separate into gametes with equal probability (principle of segregation).

    Independent and Mutually Exclusive Events

    • Independent Events: If the outcome of the first event does not influence the next.

      • Example: What is the chance of rolling a four the first time and the second time?

    • Mutually Exclusive Events: If one event excludes the occurrence of another.

      • Example: What is the chance of rolling either a three or a four?

    Conditional Probability

    • Incorporate additional information into probabilities.

    • Example: Probability that a tall F2 plant is genotype Tt given that it is x tt.

    • Understanding subsets of progeny or known phenotypes aids in identifying genotypes.

    Test Crosses

    • Test cross: A cross between an individual with an unknown genotype with a homozygous recessive individual.

    • Definition - Backcross: A cross between an F1 individual and either of the parental genotypes.

    Mendelian Traits

    • Definition: Traits influenced by a single gene with two alleles (one dominant, one recessive).

    • Traits studied by Mendel were discrete (two distinct forms) and controlled by a single gene not greatly influenced by environment.

    Examples of Mendelian Characteristics and Diseases

    1. Albinism: Caused by OCA2 allele with a large deletion resulting in no melanin production (recessive phenotype).

      • Location: Chromosome 15q12-q13.1.

    2. Blond Hair: Individuals with two copies of the tyrosinase-related protein 1 (TYRP1) allele with a C to T transition exhibit blond hair (recessive phenotype).

      • Location: Chromosome 9 p23.

    3. Huntington’s Disease: Caused by CAG nucleotide repeat mutation in the Huntington gene on Chromosome 4; occurs if at least one mutated allele is present (dominant disease).

    4. Cystic Fibrosis: Often caused by a 3 bp deletion in CFTR gene on chromosome 7q31.2; occurs when both alleles carry the mutation (recessive disease).

    Interactions Among Genes and Environment

    • Most traits do not follow simple Mendelian inheritance; environmental factors and complex interactions among genes play a role.

    • Examples include human traits such as height, weight, skin color, and disease susceptibility governed by multiple alleles and gene interactions.