Rh Inheritance

The Rh blood group system (BGS) , with more than 40 antigens, is the most complex BGS. The most significant antigen is D, followed by C, E, c, and e antigens. For more detailed information about Rh please consult resources in Suggested Reading. For purposes of understanding basic Rh inheritance, only the Fisher-Race theory will be presented here.

Fisher-Race Theory

This theory is named after the two British workers who proposed it in the 1940's. Although too simplistic to explain this complex system, the theory is useful to explain routine inheritance of D, C, E, c, and e antigens. The main tenets of the theory are as follows:

  1. Rh inheritance is controlled by 3 closely linked loci on each chromosome of a homologous pair (Figure 1-17).

  2. Each locus has its own set of alleles which are Dd , Cc , and Ee . The D gene is dominant to the d gene, but Cc and Ee are co-dominant. Today we know that the d gene does not exist; when used it represents absence of the D gene.

  3. The 3 loci are so closely linked that crossing-over does NOT occur, and the 3 genes on one chromosome are always inherited together (Figure 1-18).

The inheritance of the Rh system is not yet fully known. However, Rh genes have been cloned using the methods of DNA technology. Restriction fragment length polymorphism (RFLP) analysis suggests that Rh is controlled by two closely linked genes: one that encodes a polypeptide bearing the D antigen and a second that encodes C/c and E/e antigens. Unravelling the complexities of the Rh genome is currently an area of active research.

Below is the Medline abstract of one of the major papers published on this topic.

Source: Mouro I, Colin Y, Cherif-Zahar B, Cartron JP, Le Van Kim C. Molecular genetic basis of the human Rhesus blood group system. Nature Genetics 1993; 5(1):62-5.

The Rhesus (Rh) blood group locus is composed of two related structural genes, D and CcEe, that encode red cell membrane proteins carrying the D, Cc and Ee antigens. As demonstrated previously, the RhD-positive/RhD-negative polymorphism is associated with the presence or the absence of the D gene. Sequence analysis of transcripts and genomic DNA from individuals that belong to different Rh phenotypes were performed to determine the molecular basis of the C/c and E/e polymorphisms. The E and e alleles differ by a single nucleotide resulting in a Pro226Ala substitution, whereas the C and c alleles differ by six nucleotides producing four amino acid substitutions Cys16Trp, Ile60Leu, Ser68Asn and Ser103Pro. With the recent cloning of the RhD gene, these findings provide the molecular genetic basis that determine D, C, c, E and e specificities.

Terms to look up

ABO BGS Rh BGS Other BGS