Patterns of Heredity, Molecular & Population Genetics Review

Patterns of Heredity

• Core Vocabulary
  • Gene – heritable unit of DNA that encodes a product (RNA or protein).
    • Example: the gene coding for β-globin on chromosome 11.
  • Allele – alternative version of a gene found at the same locus.
    • Example: I^A, I^B, i alleles of the ABO blood-group gene.
  • Phenotype – observable trait or biochemical property resulting from genotype & environment.
    • Example: type A blood, tall pea plant, sickle-cell anemia.
  • Genotype – the combination of alleles an individual possesses.
    • Example: I^A i (heterozygous), aa (homozygous recessive).
  • Heterozygous – two different alleles at a locus (e.g., Aa).
  • Homozygous – identical alleles at a locus (e.g., AA or aa).
  • Dominant – allele expressed in the heterozygote; masks recessive.
    • Example: A in Aa.
  • Recessive – expressed only when homozygous; masked by dominant.
    • Example: a in individuals with genotype aa.

Meiosis

• Purpose – produce four genetically unique, haploid (n) gametes for sexual reproduction.
• Division I (Meiosis I – Reductional)
  1. Prophase I
     • Chromatin condenses, homologous chromosomes pair (synapsis) forming tetrads.
     • Crossing over: non-sister chromatids exchange segments at chiasmata → new allele combinations; occurs specifically in pachytene sub-stage.
  2. Metaphase I
     • Tetrads align on metaphase plate; orientation of each homologous pair is random ⇒ independent assortment.
  3. Anaphase I
     • Homologous chromosomes disjoin and migrate to opposite poles (sister chromatids stay together).
  4. Telophase I/Cytokinesis
     • Two haploid cells form; chromosomes still duplicated.
• Division II (Meiosis II – Equational) (resembles mitosis)
  1. Prophase II – new spindle forms around chromosomes.
  2. Metaphase II – chromosomes (dyads) align singly at plate.
  3. Anaphase II – sister chromatids separate.
  4. Telophase II/Cytokinesis – four haploid, genetically distinct gametes.
• Key Mechanisms Creating Variation
  • Random alignment of tetrads ⇒ 2^n possible gamete types for n homologous pairs.
  • Crossing over recombines linked genes.
  • Random fusion of gametes adds a third level of diversity.
• Diagram Tip – draw homologous pairs in different colors; indicate chiasmata in Prophase I and separation differences between Anaphase I vs II.

Mendelian Inheritance

• Mendel’s Pea Experiments
  • Chose discrete traits (flower color, seed shape, etc.).
  • Performed controlled crosses; tracked traits across P, F, F generations.
  • Quantified ratios → formulated principles.
• Principle of Segregation – two alleles for a gene segregate during gamete formation; each gamete carries one allele. Evidence: F_1 monohybrids self-cross ⇒ 3:1 phenotype, 1:2:1 genotype.
• Principle of Independent Assortment – alleles of different genes assort independently if on different chromosomes (or far apart). Dihybrid cross YyRr \times YyRr ⇒ 9 : 3 : 3 : 1 ratio.
• Test Cross – cross unknown with homozygous recessive; progeny phenotypes reveal genotype.
• Rule of Multiplication – probability of combined independent events is the product of individual probabilities (video link i).
  • Example: probability of aaBB from AaBb \times AaBb = \left(\tfrac{1}{4}\right) \times \left(\tfrac{1}{4}\right) = \tfrac{1}{16}.

Non-Mendelian Patterns

• Incomplete (Intermediate) Dominance – heterozygote shows intermediate phenotype (red × white snapdragons → pink). Genotypic and phenotypic ratios match (1:2:1).
• Codominance – both alleles fully expressed in heterozygote (ABO I^A I^B blood).
• Multiple Alleles – more than two allelic forms (ABO: I^A, I^B, i).
  • Inheritance of ABO:
  – I^A & I^B are codominant; i recessive.
  – Possible phenotypes O (ii), A (I^A I^A or I^A i), B, AB.
• Epistasis – allele of one gene masks/modifies expression of another. Example: Labrador coat color (E/e controls pigment deposition).
• Pleiotropy – single gene → multiple traits (Marfan syndrome: FBN1 gene affects height, vision, aorta).
• Polygenic Inheritance – additive effect of ≥2 genes on one trait (skin color, height).
  • Phenotypes show continuous variation; often bell-shaped distribution.
• Quantifying Polygenic Traits (Chapter 5)
  • Each contributing allele adds a small, equal effect; environment further smooths distribution.

Sex-Linked Inheritance

• X-linked Traits
  • Males (XY) express recessive X-linked alleles from mother (hemizygous).
  • Carrier female (X(^{A}X^{a})) × normal male → sons 50 % affected, daughters 50 % carriers.
  • Example: red-green color-blindness, hemophilia A.
• Y-linked – only males; fathers pass to all sons (e.g., SRY gene).

Pedigree Analysis

• Standard Symbols
  • Square = male, circle = female; filled = affected; half-filled = carrier; horizontal line = mating; vertical line & brackets = siblings; Roman numerals = generation.
• Evaluating Mode of Inheritance
  • Autosomal dominant – appears in every generation; affected individuals have at least one affected parent; equal sex distribution.
  • Autosomal recessive – skips generations; consanguinity may appear; equal sexes.
  • X-linked recessive – more males affected; affected males from carrier mothers; no male-to-son transmission.
  • X-linked dominant – affected males pass to all daughters, no sons; females often less severe.
  • Y-linked – father → all sons only.

Punnett-Square Practice Pointers

• Always list gamete possibilities (respecting independent assortment).
• Homozygous dominant × heterozygous (e.g., AA \times Aa) → 100 % dominant phenotype; genotypes 50 % AA, 50 % Aa.
• Dihybrid heterozygous cross SsTt \times SStt → produce gametes: ST, St (first parent); ST, St (second). Complete 2 × 2 table to get phenotypic/genotypic ratios.
• Blood-type example: type O (ii) × type AB (I^A I^B) → offspring 50 % type A, 50 % type B.

Molecular Genetics – Mutations

• Categories of Point Mutations
  • Missense – base substitution changes codon → different amino acid (e.g., sickle-cell GAG \to GTG).
  • Nonsense – substitution converts codon to stop → truncated protein.
  • Sense (read-through) – stop codon changed to amino-acid codon → elongated protein.
  • Silent – substitution does not alter amino acid (wobble).
  • Frameshift – insertion/deletion not in multiples of 3 shifts reading frame; downstream codons altered.
• Chromosomal Errors
  • Deletion, duplication, inversion, translocation, nondisjunction (Meiosis I vs II).
• Nondisjunction Outcomes
  • Meiosis I – homologues fail to separate → gametes (n+1, n+1, n–1, n–1).
  • Meiosis II – sister chromatids fail → gametes (n+1, n–1, n, n).
• Abnormal Karyotypes
  • Aneuploidy – missing/extra chromosome (e.g., trisomy 21).
  • Polyploidy – extra sets (3n = triploidy, 4n = tetraploidy).
  • Monosomy – 2n – 1.
  • Trisomy – 2n + 1.
• Mutagens & Mechanisms
  • Base analogs (5-BU) cause mispairing.
  • Tautomeric shifts alter base pairing properties transiently.
  • Radiation (UV → thymine dimers; ionizing → strand breaks).
  • Chemical modification (alkylating agents, deaminating agents).
• DNA Repair & Fate of Damaged Cells
  • Proofreading by DNA polymerase (3'→5' exonuclease).
  • Mismatch repair, excision repair, photoreactivation, NHEJ, homologous recombination.
  • Excess damage ⇒ apoptosis (programmed cell death) or senescence (permanent cell-cycle arrest).
  • Cancer results from accumulation of mutations in proto-oncogenes & tumor suppressors.

Biotechnology Techniques

• PCR (Polymerase Chain Reaction)
  • In vitro amplification of specific DNA region via cycles of denaturation, annealing, extension.
  • Applications: diagnostics, forensics, cloning, COVID testing.
• DNA Sequencing (Sanger)
  • Dideoxynucleotides terminate synthesis; fragments sorted by electrophoresis → read sequence.
  • Used for mutation detection, phylogenetics.
• DNA Microarray
  • Thousands of probes on chip detect gene expression or SNPs simultaneously.
  • Drug response profiling, cancer subtyping.
• Southern Blot
  • DNA fragments transferred to membrane, probed by labeled DNA.
  • Detect specific sequences; RFLP analysis.
• Recombinant DNA / Gene Cloning
  • Restriction enzyme + ligase insert gene into vector → replicate in bacteria.
  • Protein production (insulin), gene therapy.
• Electrophoresis & DNA Fingerprinting – separate DNA by size; produce individual-specific banding patterns.
• Applications
  • DNA Profiling – crime scene identification, paternity.
  • Biopharming – transgenic organisms produce pharmaceuticals.
  • GMOs – crops with inserted traits (Bt corn).
  • Stem Cells – therapeutic cloning, regenerative medicine.
  • Cloning – nuclear transfer to create genetically identical organisms (Dolly).

Population Genetics & Hardy–Weinberg

• Hardy–Weinberg Equation
  p + q = 1 (allele frequencies)
  p^2 + 2pq + q^2 = 1 (genotype frequencies)
  • Predicts expected distribution in absence of evolutionary forces.
• Equilibrium Assumptions
  1. Large population (no genetic drift).
  2. Random mating.
  3. No mutation.
  4. No migration (gene flow).
  5. No natural selection.
• Calculations
  • Given recessive phenotype frequency (q^2), find q = \sqrt{q^2} then p = 1 - q to derive other genotypes.
• Natural Selection – differential reproductive success shifts allele frequencies; modes: directional, stabilizing, disruptive.
• Sources of Variation
  • Mutation – ultimate source.
  • Genetic Drift – random change; strong in small pops (bottleneck, founder effect).
  • Non-random Mating – inbreeding, assortative mating.
  • Gene Flow – migration introduces/withdraws alleles.
  • Speciation – genetic divergence leads to new species.

Quick Reference – Causes of Genetic Variation (with Examples)

• Genetic Drift – volcanic eruption reduces population → allele frequency shift.
• Founder Effect – Amish community high frequency of Ellis–Van Creveld syndrome.
• Natural Selection – peppered moth coloration shift during industrial revolution.
• Mutation – CCR5-Δ32 confers HIV resistance in some Europeans.
• Non-random Mating – self-fertilizing plants increase homozygosity.
• Speciation – Darwin’s finches radiated on Galápagos.

Study Strategy Tips

• Master definitions; use flashcards for vocabulary.
• Redraw meiosis diagrams until sequence is automatic.
• Practice Punnett squares daily; vary scenarios (autosomal vs sex-linked, multiple genes).
• For Hardy-Weinberg, write the two equations at top of every problem and label variables.
• Relate molecular techniques to real-world uses (COVID PCR tests, forensic DNA).
• Work through linked problem sets; check against these notes.