Population genetics principles

Hardy-Weinberg Equilibrium - The Genetic Status Quo

• A principle stating that allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences.

• Key Assumptions:

  • Large population size (no genetic drift)
  • Random mating
  • No mutation
  • No natural selection
  • No gene flow (migration)

• Governing Equations:

  • Allele Frequency: $p + q = 1$
  • Genotype Frequency: $p^2 + 2pq + q^2 = 1$
    • $p^2$ = Homozygous dominant
    • $2pq$ = Heterozygous
    • $q^2$ = Homozygous recessive

⭐ For a rare autosomal recessive disease, the carrier frequency (2pq) can be approximated as 2q, where q is the square root of the disease prevalence (q²).

H-W Assumptions - When Equilibrium Breaks

Hardy-Weinberg equilibrium is disrupted when evolutionary forces are at play, causing allele frequencies to change. The main drivers are:

• Non-random Mating: Stratification or assortative mating alters genotype frequencies, not necessarily allele frequencies.
• Mutation: A weak force, but the ultimate source of new alleles.
• Natural Selection: Alleles conferring survival or reproductive advantages increase in frequency.
• Genetic Drift: Random changes in allele frequencies due to chance; most pronounced in small populations.
  • Founder Effect: A new population is established by a small number of individuals.
  • Bottleneck Effect: A sharp reduction in population size from a random event.
• Gene Flow: Migration of individuals between populations, introducing new alleles.

⭐ Genetic drift has a disproportionately large effect in small populations (e.g., founder effect in isolated religious communities or bottleneck events). This is a key mechanism for rapid evolution in these groups.

Genetic Drift & Selection - Random Chance & Survival

• Genetic Drift: Random fluctuations in allele frequencies from one generation to the next; more significant in small populations.

  • Founder Effect: A small group breaks off from a larger population to establish a new colony, resulting in a non-representative gene pool.
  • Bottleneck Effect: A sharp ↓ in population size (e.g., disaster) leads to a random change in the gene pool of survivors.

• Natural Selection: Differential survival and reproduction based on phenotype.

  • Stabilizing: Favors the average phenotype (e.g., birth weight), selects against extremes.
  • Directional: Favors one phenotypic extreme.
  • Disruptive: Favors both extremes over the intermediate.

⭐ Heterozygote Advantage: A form of stabilizing selection where heterozygotes have a fitness advantage over both homozygotes. Classic example: Sickle cell trait (HbAS) confers resistance to malaria.

Clinical Calculations - The Numbers Game

• Hardy-Weinberg Principle: Models stable allele/genotype frequencies. Assumes: no mutation, selection, drift, gene flow & random mating.
  • Allele Frequency: $p + q = 1$
  • Genotype Frequency: $p^2 + 2pq + q^2 = 1$
• Core Variables:
  • p, q: dominant, recessive allele frequencies.
  • q²: autosomal recessive (AR) disease frequency.
  • 2pq: carrier (heterozygote) frequency.
• AR Calculation:
  • Disease incidence gives $q^2$.
  • Allele frequency: $q = \sqrt{q^2}$.
  • Carrier frequency = $2pq$. For rare diseases ($p \approx 1$), carrier frequency $\approx 2q$.

⭐ For X-linked recessive disorders, the frequency of affected males equals the allele frequency q, and the frequency of female carriers is 2pq.

High‑Yield Points - ⚡ Biggest Takeaways

• Hardy-Weinberg equilibrium requires five key assumptions: no mutation, random mating, no gene flow, no genetic drift, and no natural selection.
• Allele frequency is p + q = 1; genotype frequency is p² + 2pq + q² = 1.
• In autosomal recessive diseases, the carrier frequency is calculated as 2pq.
• Genetic drift is the random change in allele frequencies in small populations, seen in founder and bottleneck effects.
• Natural selection drives evolution by favoring alleles that increase fitness (survival and reproduction).