Molecular Basis of D Weak and D Partial

Subject: Healthcare Research
Pages: 3
Words: 781
Reading time:
3 min
Study level: College

How Weak D is made based on the molecular basis

By definition, the weak D phenotype (formerly referred to as Du) is the weak form of the D antigen. During the routine D ty, ping it reacts with a group of anti-D but not with others when an immediate spin is done. The weak D cells possess a fewer number of D antigens per cell than in normal Rh-positive cells. The prevalence of weak D people is as high as 20% in Caucasians and as low as 0.5 % in some Asian populations. However, this ratio depends on the method used, reagent type, and the racial mix (Frohmajer, et al. 2000, p. 2700). Moreover, the frequency of weak D among blacks is considered to be high than in whites. The D antigen is encoded by the RHD gene with no antithetical counterpart. The D antigen consists of many different epitopes and people whose D positive RBC lack one or more of these epitopes (partial D) can make anti-D. The weak D types have been numbered weak D type 1 to type 53. Although these weak D phenotypes are associated with weakness of D expression, it is only possible to distinguish them from each other by gene sequencing. The proteins have one or more amino acid substitutions within either the membrane-spanning domains or the cytoplasmic loops of the protein but are not exposed to the outside of the membrane. The weak D phenotype is made from three mechanisms namely gene interaction (position type), mosaic type (partial D), and hereditary. In the gene interaction method, a C gene positioned in the transposition to D may suppress the D gene. For instance, in the genotypes CDE/Cde, the C gene in the trans to the D gene can suppress it and the resultant gene is weak D antigen. However, persons with the gene interaction type of weak D can transmit a normal D gene to their offspring. Thus, this type of weak D is not directly inherited (Frohmajer, et al. 2000, p. 2704). Typically, the method used to detect weak D cells is referred to as the Du test. The Du test involves an indirect anti-globin test using the patient’s red cells and an IgD anti-D. The Du test is controlled by doing a DAT on the test cells. This serves as an auto-control that discloses whether the cells are sensitive to antibodies in vivo. However, if DAT is positive, the Du test becomes invalid as it will show positive results whether or not the patient is a weak D (Wagner, et al. 1999, p. 387).

How Partial D is made based on the molecular basis

Partial D proteins have amino acids changes (from normal D) within one of or more of the predicted external loops of D polypeptide. The partial D phenotypes have been given symbols s uch as DIIIa, DV,I, DBT, and DFR. They can be distinguished from each other by serological means and molecular methods. The hereditary mechanism is not influenced by the position of the C gene and D gene. It is controlled by D genes that produce a smaller number of D antigens per cell than in the normal D gene. The partial D or mosaic type is hereditary and consists of several parts of the D antigen. Generally, people are identified as having the partial D phenotype when their anti-D is made an alloantibody. People with D-positive inherit a gene that develops into all parts of the D mosaic. Most people with weak D inherit a gene that produces only part of the mosaic (Wagner, et al. 1999, p. 386). The partial D has been associated with a single point mutation or gene rearrangement of RHCE into RHD, or RHD into RHCE) which occurs because of a high degree of homology of the two genes. The three types of partial D result from different homologous exchanges of exons from RHCE into RHD. In type I, exons 4 and 5, in type II exons 4 and 6, and in type III exons 3 and 6. The main difference between weak d and partial D phenotypes is that weak D is associated with normal RHD. People with weak D phenotype (whose RBC have a weak expression of all the D epitopes) do not make anti D while people with the partial D phenotypes (whose RBC expresses a qualitative altered partial D antigen) can make anti D (Wagner, et al. 1999, p. 393).


  1. Frohmajer, A., Ladewig, B., Eicher, N. 2000, ‘Weak D alleles express distinct phenotypes’, Blood, vol. 95, pp. 2699-708
  2. Wagner, F., Gassner ,Muelleraller, T.H., et al. 1999, ‘Molecular basis of weak D phenotypes’, Blood, vol. 93, pp. 385–93. (1999)