The Hardy-Weinberg principle states that allele and genotype frequencies in a population remain constant from generation to generation in the absence of evolutionary forces. It provides the foundation for calculating carrier frequencies and disease prevalence.
- Equation: p^2 + 2pq + q^2 = 1, where p = frequency of dominant allele, q = frequency of recessive allele, and p + q = 1
- p^2 = frequency of homozygous dominant (AA)
- 2pq = frequency of heterozygous carriers (Aa)
- q^2 = frequency of homozygous recessive (aa). This is usually the disease prevalence for AR conditions.
- Large population size (no genetic drift)
- Random mating
- No mutation
- No migration (gene flow)
- No natural selection
Problem: Cystic fibrosis affects 1 in 2,500 individuals of European ancestry. What is the carrier frequency?
Solution:
- q^2 = 1/2,500
- q = 1/50
- p = 1 - 1/50 = 49/50
- 2pq = 2 x (49/50) x (1/50) = 98/2,500 = approximately 1/25
Answer: Approximately 1 in 25 individuals of European ancestry are CF carriers.
- Calculate carrier frequency from disease incidence
- Determine probability two carriers will meet and have an affected child
- Recognize when Hardy-Weinberg assumptions are violated (consanguinity, founder effect, genetic drift)
"q-squared is the disease": for autosomal recessive conditions, start with q^2 (disease frequency), take the square root to get q, then calculate 2pq for carrier frequency. Always start from what you know.
"DRuMS No More": the 5 assumptions: Drift (large pop), Random mating, Mutation (none), Selection (none), Migration (none). If any are violated, HWE does not hold.