Genetic Control of Rh Factor

Beyond the A and B antigens, human red cells carry a third, independent surface antigen — the Rh factor, more precisely the 'D' antigen of the Rh blood group system — first found in the blood of the rhesus monkey (Macaca rhesus) by Karl Landsteiner and Alexander Wiener in 1940, and shortly afterwards in humans too. A person carrying the D antigen is Rh-positive (Rh+); a person without it is Rh-negative (Rh-). Unlike ABO antibodies, anti-D antibodies are not naturally present in anyone's plasma from birth — an Rh-negative person only starts making them after their immune system is first exposed to Rh-positive red cells, which is what makes Rh incompatibility a delayed, sensitisation-driven problem rather than an immediate one (covered next, in 4.3.1).

Two competing genetic models were proposed to explain how Rh type itself is inherited, and this section works through both. The Fisher and Race hypothesis — the model in wider use today, using the 'Cde' naming convention — holds that Rh type is governed not by one gene but by three separate, tightly linked gene pairs (C/c, D/d and E/e) sitting at three adjacent loci on one chromosome (Fig. 4.1), so a full genotype is written as something like CDE/cde. Under this model, any genotype carrying at least one dominant D allele gives the Rh-positive phenotype, and only the double-recessive dd genotype gives Rh-negative. The alternative Wiener hypothesis instead proposed a single Rh locus with eight possible alleles (R1, R2, R0, Rz, r, r1, r11, ry); here again, any genotype carrying a dominant 'R' allele is Rh-positive, and the various dou …