Zygosity:
Since each RBC antigen is the product of a gene, patients may be deemed heterozygous or homozygous for any antigen in question. Zygosity can in turn be inferred by looking at how many different alleles of a certain antigen a patient possesses.
Examples of alleles include C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, and S/s. For the most part the difference in alleles is the result of a single nucleotide polymorphism, representing the difference of one amino acid.
- Note: there are exceptions to this rule. The Lewis antigens (Lea and Leb) and P antigens are actually the results of complex interactions between multiple gene products and as a result cannot be thought of in terms of zygosity.
If a patient expresses only one of two alleles, it can be assumed that they are homozygous for the allele that they do express. For example, a patient who is C+ but c- is said to be homozygous for the C antigen, whereas a patient who is both C+ and c+ is heterozygous for both antigens.
To determine D zygosity, look at the Weiner haplotype. Remember that capital “R” represents the D allele, whereas lower case “r” represents the absence of the D allele (e.g. no RhD product). Therefore, homozygous D cells are captured by the notation R1R1, R2R2, R1R2, etc, whereas hemizygous expression would be indicated by R1r, R2r, etc. Remember, there is no minor allele for the D antigen.
Zygosity is a very important concept in blood bank serology since it often correlates with “dosage”, or the density of antigen expression on the RBC surface. Thus, in a patient with an anti-C antibody in their plasma, stronger reactions are expected against cells that are C+c- than those that are C+c+.
Conversely, the presence of an anti-C antibody can be more confidently ruled out by showing lack of reactivity against C+c- cells than C+c+ cells. The same is true when performing rule-outs against most other antigens: whenever possible, a homozygous cell should be used.
Next page: Approach to the Antibody Panel