Comprehensive University Lecture Notes on Principles of Genetics

Foundations of Genetics and Ploidy

Connection to Meiosis: * Last sessions covered meiosis, the process by which gametes are produced. * Gametes: These are haploid, meaning they contain only half the amount of DNA found in a somatic cell. * Somatic Cells: These are diploid, containing a full complement of DNA.
Chromosomal Counts and Ploidy Designation: * In humans, somatic cells contain $46$ chromosomes. Diploidy is designated as $2n$ . * In humans, gametes (eggs and sperm) contain $23$ chromosomes. Haploidy is designated as $n$ . * In plants, gametes are referred to as the pollen (male) and the ovule (female).
Fertilization and Development: * The fusion of two gametes (sperm and egg) results in a zygote. * The formula for ploidy in fertilization is $n + n = 2n$ . Therefore, the zygote is diploid. * The zygote undergoes replication via mitotic cell division to develop into a full-grown individual.
Definition of Genetics: The study of the results of the fusion between two gametes and the likely physical, biochemical, or physiological traits found in the offspring.

The Work of Greg Mendel

Historical Context: Greg Mendel is considered the father of genetics. He operated without knowledge of DNA or chromosomes but proposed that parents influence the appearance of offspring through certain "factors."
Model Organism: Mendel worked with a particular species of pea plants.
True Breeding Varieties: * Mendel used true breeding varieties, which consistently produce identical offspring. * Example: A pea plant with white flowers always produces seeds that grow into plants with white flowers. * Example: A variety with yellow pods only produces plants with yellow pods.
Experimental Controls: * Pea plants naturally have both male and female organs in the same flower. * The flowers remain closed, which prevents cross-contamination by pollinators like bees or butterflies. * Mendel manually controlled variables by using a thin paintbrush to transfer pollen from the male organ of one flower to the ovule (female organ) of another plant.
Generations in Genetic Crosses: 1. P Generation: The Parental generation consisting of two true-breeding parents. 2. F1 Generation: The offspring resulting from the cross of the P generation. 3. F2 Generation: The offspring resulting from the cross of two individuals from the F1 generation.

Mendelian Characteristics and Observations

The Seven Traits: Mendel focused on seven consistent, observable characteristics in pea plants: 1. Flower color (Purple vs. White). 2. Seed color (Yellow vs. Green). 3. Seed shape (Round vs. Wrinkled). 4. Pod color. 5. Pod shape. 6. Flower and pod position. 7. Plant height (Tall vs. Dwarf).
Discovery of Dominance: * When Mendel crossed purple flowers with white flowers, all F1 offspring had purple flowers. * When crossing yellow seeds with green seeds, all F1 offspring had yellow seeds. * When crossing round seeds with wrinkled seeds, all F1 offspring had round seeds. * Dominant Trait: The characteristic that is expressed in the F1 generation. * Recessive Trait: The characteristic that disappears in the F1 generation only to reappear later. * Distinction: Dominant does not mean "good," and recessive does not mean "bad."
Types of Crosses: * Monohybrid Cross: A genetic cross where only one trait/gene is considered, and all others are ignored. * Dihybrid Cross: A genetic cross involving the outcome of two different characteristics simultaneously.

Modern Molecular Genetics: Genotypes and Phenotypes

Genes and Proteins: * Genes are segments of DNA that code for proteins. * Proteins are the active agents that determine physical appearance and biochemical functions. * The Central Dogma: DNA $\rightarrow$ RNA $\rightarrow$ Protein.
Alleles: * Alleles are different versions or precise sequences of nucleotides for the same gene. * Every diploid individual has two alleles for each gene (one on each homologous chromosome). * Genotype: The description of an individual's specific alleles (represented by letters). * Phenotype: The observable trait or physical expression (e.g., tall, short, wavy hair, widow's peak, or internal markers like lactose intolerance).
Expressing Genotypes: * Homozygous Dominant: Carrying two dominant alleles (e.g., $SS$ or $PP$ ). * Heterozygous: Carrying one dominant and one recessive allele (e.g., $Ss$ ). In Mendelian genetics, the dominant phenotype is expressed. * Homozygous Recessive: Carrying two recessive alleles (e.g., $ss$ ). This is the only way the recessive phenotype is expressed.
Homologous Chromosomes: These share the same length, carry the same genes, and possess those genes at the same locus (position).

Genetic Probability and Ratios

Mendel's 3:1 Ratio: * In the F2 generation (the cross of two heterozygous F1 plants), Mendel consistently observed a ratio of three individuals with the dominant phenotype to one individual with the recessive phenotype ( $3:1$ ). * This ratio held true for all seven characteristics studied.
The Contingency Diagram (Punnett Square): * Used to calculate the probability of genotypes and phenotypes in offspring. * Gamete Formation: Because gametes are haploid, they can only carry one allele from a pair. A heterozygous individual ( $Dd$ ) produces two types of gametes: half with the $D$ allele and half with the $d$ allele. * Example Cross (Heterozygous x Heterozygous): * Genotypic Frequency: $25\%$ homozygous dominant ( $DD$ ), $50\%$ heterozygous ( $Dd$ ), and $25\%$ homozygous recessive ( $dd$ ). This is a $1:2:1$ ratio. * Phenotypic Frequency: $75\%$ Dominant (Tall) and $25\%$ Recessive (Dwarf). This is a $3:1$ ratio. * Probability Note: While the table suggests ratios, genetics involve chance. It is possible (though improbable) for two heterozygous plants to produce only dwarf offspring.

Non-Mendelian Inheritance Patterns

Incomplete Dominance: * The dominant allele is not completely dominant over the recessive allele, resulting in an intermediate phenotype for heterozygous individuals. * Example: Snapdragon Flowers. * $RR$ = Red flowers. * $rr$ = White flowers. * $Rr$ = Pink flowers.
Codominance: * Multiple alleles are dominant and expressed simultaneously when present. * Example: ABO Blood Types. * Controlled by the production of proteins called immunoglobulins at the surface of red blood cells. * Allele $I^A$ produces Immunoglobulin A ( $IgA$ ). * Allele $I^B$ produces Immunoglobulin B ( $IgB$ ). * Allele $i$ (or small i) produces neither. * Genotype $I^A I^B$ results in blood type AB, where both proteins are expressed equally.
Pleiotropy: * One single genotype/gene gives rise to multiple, seemingly unrelated phenotypes. * Example: Cystic Fibrosis. * Caused by a mutation in the allele encoding the CFTR protein. * Defective CFTR causes multiple medical phenotypes across different organ systems.
Polygenic Inheritance: * The opposite of pleiotropy; multiple genes interact to determine a single phenotype. * Most human characteristics are polygenic, including skin color and eye color. * This explains why fraternal twins can possess significantly different skin tones or appearances.

Human Disorders and Chromosomal Location

Autosomal Disorders: * Caused by alleles located on the autosomes (the $22$ pairs of non-sex chromosomes). * Example: Waldenberry syndrome. * Symptoms: Piercing blue eyes, white patch of hair, discolored skin, and occasionally poor hearing. * Despite global distribution (e.g., Haiti, Sierra Leone), it is controlled by single autosomal genes.
Sex-Linked (X-Linked) Genes: * Located on the X chromosome. * Examples include Hemophilia (blood clotting disorder), muscular dystrophy, and red-green color blindness.

Epigenetics

Definition: The study of how the environment influences the expression of genes into proteins.
The Paradigm Shift: Understanding that it is not "nature or nurture" but rather "nature and nurture."
Clarification on Acquired Traits: External alterations to phenotype (e.g., Sammy Sosa bleaching his skin) are physical modifications and are not examples of epigenetic gene expression changes.