The ‘Rhesus’ (Rh) blood group in man

 A very interesting series of alleles affecting the antigens of human blood has been discovered through the work of Landsteiner, Wiener, Race, Levine, Sanger, Mourant, and several others.

The original discovery was that the red blood cells are agglutinated by a serum prepared by immunizing rabbits against the blood of Rhesus monkey (Macaca rhesus). The antigen responsible for this reaction was consequently called as Rhesus factor and the gene that causes this property was denoted as R-r or Rh-rh.

The Rh factor is simply a protein that is found on the covering of the red blood cells. If the red blood cells have this protein, then it is called Rh-positive. If the blood cells don't have this protein, then it is called Rh-negative. Just as everyone inherits ABO genes, every person inherits one Rh factor gene from each parent. The Rh-positive gene is the dominant gene when paired with an Rh-negative gene.

Interest in this factor was stimulated by Levine’s study of a characteristic form of anemia, known as Erythroblastosis foetalis, which occurs occasionally in newborn infants. It was found that the infants suffering from this anemia are usually Rh-positive and so are their fathers, but their mothers are Rh-negative. The origin of the disease is explained as follows: The Rh+ fetus developing in the uterus of an Rh– mother causes the formation of the mother’s bloodstream of anti-Rh antibodies. These antibodies, especially as a result of a succession of several Rh+ pregnancies, gain sufficient strength in the mother’s blood so that they may attack the red blood cells of the fetus. The reaction between these antibodies of the mother and the red cells of her unborn child provokes hemolysis and anemia; this may be serious enough to cause the death of the newborn infant or abortion of the fetus.

The bloodstream of a mother who has had an erythroblastotic infant is a much more potent and convenient reagent than sera of rabbits, immunized by the blood of rhesus monkey for testing the blood of other persons to distinguish Rh+ from Rh– individuals using such sera from women who had erythroblastotic infants, it was discovered that: there exist not one but several kinds of Rh+ and Rh- persons. There are several different Rh antigens that are detected by specific antisera. Thus, an Rh– woman immunized during pregnancy by the Rh+ children may have in her blood serum antibodies, that agglutinate not only Rh+ red cells but also cells from a few persons known to be Rh–.

By selective absorption two kinds of antibodies may be separated from such a serum, one known as anti-D which agglutinates (coagulates) only Rh+ cells, the other known as anti-C which agglutinates particular rare types of Rh–. Another specific antibody, known as anti-c agglutinates all cells that lack C. With these three antisera, six types of blood can be recognized. Studies of parents and children show that persons of type Cc are heterozygous for an allele C determining C antigen. CC persons are homozygous for C and cc are homozygous for c. There is obviously no dominance, each allele producing its own antigen in the heterozygote as in the AB blood type.

No antiserum is available for detecting d, the alternative to D. D+ persons may be heterozygous or homozygous. However, the genotypes of such persons may be diagnosed from their progeny; for example, a D+ person who has a d– the child is thereby shown to be Dd. Two other specific antibodies, anti-E and anti-c have been found. These detect the antigens E and e determined by a pair of alleles E and e. The three elementary types of antigens C-c, D, and E-e, occur in fixed combinations that are always inherited together as alleles of a single gene. Wiener and Fisher showed the existence of a series of eight different alternative arrangements of these three types of Rh antigens and expressed them by means of the following symbols.

Thus, allelism is determined by cross-breeding experiments. If one gene behaves as dominant to another the conclusion is that they are alleles and that they occupy identical loci in homologous chromosomes. They should occupy identical loci in the chromosome. When more than a pair of alleles occur in respect of any character in inheritance the phenomenon is known as multiple allelism. There is not much difference between the two theories of Wiener and Fisher. Wiener's opinion is that there are multiple variations of one gene whereas according to the view of Fisher three different genes lying very close together are responsible for differences.