ABO and Rh Inheritance in a Second Pregnancy
A couple attends a genetic counselling clinic. The woman is blood group A and Rh-negative; her mother was blood group O. The man is blood group AB and Rh-positive; his father was Rh-negative. Their first child is blood group B and Rh-positive, born after an uncomplicated delivery. The couple plans a second child and asks about the chance that the baby will be group B and Rh-positive, and about hemolytic disease of the newborn. No anti-D immunoglobulin was given after the first delivery. The clinic uses the standard ABO and Rh inheritance model: A and B alleles are codominant, O is recessive, and Rh-positive (D) is dominant over Rh-negative (d). The parents' ABO and Rh phenotypes are confirmed; no rare alleles or cis-AB are considered.
1. Determine the parental genotypes at the ABO and Rh loci, explaining how each is inferred.
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ABO: the woman is group A but her mother is group O (OO), so the woman must have inherited O from her mother and can only be AO. The man is group AB, so he is AB. Their first child is group B: the child must have received B from the father and O from the mother, giving BO. This is consistent with AO × AB, which can produce A, B, and AB children. Rh: the woman is Rh-negative, so she is dd. The man is Rh-positive but his father is Rh-negative (dd), so the man must have inherited d from his father and D from his mother; he is Dd. Thus the parental genotypes are: woman AO dd; man AB Dd.
2. Calculate the probability that the second child will be group B and Rh-positive. Show the reasoning for each locus.
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ABO cross AO × AB: possible gametes from the mother are A or O; from the father, A or B. Offspring: AA (A), AO (A), AB (AB), BO (B), each 1/4. So P(child group B) = 1/4. Rh cross Dd × dd: offspring Dd (Rh-positive) with probability 1/2 and dd (Rh-negative) with probability 1/2. ABO and Rh loci assort independently, so P(B and Rh-positive) = 1/4 × 1/2 = 1/8, or 12.5%. Note that group B requires the mother's O allele, which is independent of the Rh result.
3. Assess the risk of Rh hemolytic disease of the newborn in the second pregnancy and explain whether anti-D immunoglobulin is indicated now.
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Rh risk: mother dd, first child Rh-positive (Dd). At delivery, fetal D-positive red cells can enter the maternal circulation and sensitize her to D antigen; no anti-D was given, so sensitization is possible. In a second pregnancy, if the fetus is Dd (50% chance), maternal anti-D IgG can cross the placenta and cause hemolytic disease of the newborn (HDFN), with anemia and jaundice. The father being Dd means a 50% chance the fetus is Rh-negative and not at risk. Management: check the mother's indirect Coombs/antibody titer now. If she is not sensitized, anti-D prophylaxis is indicated (typically at 28 weeks and within 72 h after delivery of an Rh-positive baby). If she is already sensitized, anti-D will not help; the pregnancy needs monitoring by antibody titers and fetal middle cerebral artery Doppler, with possible intrauterine transfusion. ABO incompatibility (mother A, baby B) can cause mild HDFN but is usually less severe than Rh disease and does not change the Rh prophylaxis decision.