The Family with Sickle Cell Trait
A couple attend a clinic. The woman has sickle cell trait (heterozygous HbA/HbS) and the man also has sickle cell trait. They have one child with sickle cell anaemia (HbS/HbS) and are expecting a second child. They ask three things: the chance the new baby will have sickle cell anaemia, whether their affected child could have been avoided, and whether the trait protects anyone in the family. A relative claims that because both parents are healthy, the disease cannot be inherited, and that the affected child must have caught an infection.
1. Calculate and explain the probability that the second child will have sickle cell anaemia, and explain why both parents are healthy.
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Each parent has genotype HbA/HbS. Each gamete carries HbA with probability 1/2 and HbS with probability 1/2. The four equally likely combinations are HbA/HbA, HbA/HbS, HbS/HbA and HbS/HbS, so the chance of HbS/HbS is 1/4, or 25%. The parents are healthy because HbS is recessive to HbA at the level of red cell shape: heterozygotes make both normal and sickle haemoglobin, and the normal haemoglobin is sufficient to keep most red cells normal, so symptoms do not appear. The affected child inherited HbS from both parents. The relative's infection claim is wrong: this is a single-gene recessive condition, and the family pattern (two unaffected parents, one affected child) fits recessive inheritance exactly.
2. Explain the claim that the trait protects carriers, and state why the trait persists at high frequency in some populations.
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HbA/HbS individuals have some red cells that sickle under low oxygen, which reduces the ability of the malaria parasite Plasmodium to complete its life cycle in the blood. In regions where malaria is common, carriers therefore survive and reproduce better than HbA/HbA individuals, who are fully susceptible to severe malaria. HbS/HbS individuals are severely affected and often do not reproduce. This is heterozygote advantage: the HbS allele is kept in the population because carriers have the highest fitness, even though homozygotes are disadvantaged. In a malaria-free country the advantage disappears, but the allele frequency remains high in populations with ancestry from malarial regions because the allele has not had time to be removed. The judgement is that the trait is protective only against malaria, not against the anaemia itself.