Pedigree: calculating disease risk
With autosomal recessive diseases, two unaffected parents can have an affected child. From the pedigree you can work out how likely relatives are to be carriers and how high the risk is for more children.
Rules
- Affected child of unaffected parents → both parents Aa, recessive inheritance
- Each further child: 1/4 affected
- Unaffected sibling: 2/3 carrier (aa is ruled out)
- Risk for a child: P(parent 1 carrier) × P(parent 2 carrier) × 1/4
Your turn
Three problems on this topic. Type probabilities as a percentage number, e.g. 18.75.
Task
Two unaffected parents have a child with cystic fibrosis (autosomal recessive). (1) What is the risk that their next child is affected? (2) What is the probability that an unaffected sibling is a carrier? (3) This unaffected sibling has a child with a partner from the general population, in which 1 in 25 people is a carrier. What is that child’s risk of being affected?
Risk for the next child in %
Unaffected sibling is a carrier in %
Risk for the sibling’s child in %
Probabilities as a percentage number (25 or 18.75), rounded to 2 decimal places; allele frequencies as a decimal (0.02).
Worked example
Two unaffected parents have a child with cystic fibrosis (autosomal recessive). (1) What is the risk that their next child is affected? (2) What is the probability that an unaffected sibling is a carrier? (3) This unaffected sibling has a child with a partner from the general population, in which 1 in 20 people is a carrier. What is that child’s risk of being affected?
Worked solution
- 1.The affected child is aa, so both unaffected parents are Aa → Aa × Aa: each child 1/4 aa = 25%
- 2.An unaffected sibling is AA, Aa or aA (aa is ruled out): 2 of 3 options are carriers → 2/3 = 66.67%
- 3.The child is affected only if both are carriers and both pass on a: 2/3 × 1/20 × 1/4 = 0.8333% ≈ 0.83%
Typical mistake: Using 1/2 instead of 2/3 for the unaffected sibling. Since the sibling is unaffected, aa is ruled out: of the three remaining options (AA, Aa, aA) two are carriers.
Common questions
Why 2/3 and not 1/2?
Of the four options AA, Aa, aA, aa, aa is ruled out because the sibling is unaffected. Of the three left, two are carriers.