Molecular Genotyping - Introduction
The application of DNA analysis to typing blood group antigens started in the early 1990s but is not yet widely available. Molecular methods exist for typing Rh (RHD and RHCE), Kell (K & k), Duffy (Fya & Fyb), and Kidd (Jka &
In perinatal testing programs, molecular typing can determine the Rh type of the mother, father, and fetus and may be done if the mother has anti-D or another antibody known to cause HDFN.
More specifically, if available, DNA methods are typically used in these circumstances:
- For women who type as weak D in serologic tests, to determine the Rh genotype of the mother to identify if she is partial D or weak D;
- For women who have made anti-D, to determine the Rh genotype of the father to see if fetal monitoring is needed;
- For women who have made anti-D, to determine the Rh type of the fetus if the father is heterozygous for RhD or unavailable for testing. Fetal blood typing can be done using fetal DNA from cells obtained by amniocentesis or by testing cell-free, fetal-derived DNA present in maternal plasma at 5 weeks gestation and later.
Like all diagnostic methods, DNA typing has limitations and is not 100% sensitive and specific. For example:
- The blood group's molecular basis may be unknown;
- Not all alleles in ethnic populations are known;
- Rare mutations in the RHD and other genes may not be detected;
- Silencing changes (switching off of a gene) may affect antigen expression;
- Fetal typing using amniotic fluid may give false-negative results because of maternal cell contamination.