Molecular Diagnostics

Non-invasive fetal genotyping from maternal blood

This service was introduced in May 2001. Cell-free fetal DNA may be found in maternal plasma throughout pregnancy (Lo et al, Am. J. Hum. Genet. 62:768-775, 1998). This DNA can be obtained by maternal venepuncture without risk to the fetus. Fetal DNA in maternal plasma may be used to identify the blood group of the fetus, even in the presence of maternal DNA. At present the technique is validated for RhD, Rhc, RhE, RhC and Kell typing. The amount of fetal DNA in maternal plasma is known to increase during pregnancy, therefore at early stages it may be too low to detect and we advise that the test be used only for pregnancies which have progressed beyond the 16th week for RhD, Rhc, RhE and RhC and the 20th week for Kell.

Technical aspects

Limitations of non-invasive genotyping

Please note that we cannot confirm the presence of fetal DNA in a maternal blood sample. There is a possibility that failure to detect the fetal gene of interest may be due to undetectable levels of fetal DNA in the sample and may not indicate that the fetus is negative for that blood group or lacks the Y chromosome. There is a theoretical possibility that in a very small number of pregnancies we may detect fetal DNA from a fetus that has subsequently been lost as a result of the ‘vanishing twin’ phenomenon (Landy & Keith, 1998). In addition, due to the complexity of some blood group systems, there remains the possibility that on very rare occasions, genotyping results may not correspond to phenotype by conventional serology.

Blood group genotyping from blood, amniotic fluid or chorionic villi

IBGRL Molecular Diagnostics uses various techniques to determine blood group genotype: Allele-specific PCR, real-time PCR (allelic discrimination using Taqman probes) and HEA Beadchip. The technique used will depend on the test requested and the current workload in the laboratory.

Available genotyping tests:

  • Standard Blood Group Genotype 

RhD, c, C, E, e, K/k, Jka /Jkb , Fya /Fyb , MN, S/s, U-/ Uvar

  • Extended Blood Group Genotype

RhD, c, C, E, e, V, VS, K/k, Jka /Jkb , Fya /Fyb , Fyx , MN, S/s, U-/ Uvar, Doa /Dob , Jsa /Jsb , Kpa /Kpb , Lua /Lub , Coa /Cob , Dia /Dib , Sc1/ Sc2, LWa /LWb

  • Extended Genotype: Haemoglobinopathy Patient Array 

This genotyping test array is particularly suited for haemoglobinopathy patients.

RhD, C, c, E, e, (including common RhD, C and e variants),V, VS, hrB , hrS , K/k, Kpa /Kpb, Jsa /Jsb, Doa /Dob, Fya /Fyb, Jka /Jkb, M/N, S/s, U-, Uvar

Limitations and caveats of blood group genotyping

The molecular biology of blood groups, and particularly of the Rh system, is complex and genetic differences may be found in ethnic groups. It remains a possibility that on very rare occasions genotyping results may not correspond to serological phenotype. Clinical decisions should not, therefore, rest solely on genotyping results.

People who have received a transplant following which incomplete engraftment has taken place may exhibit chimerism in their blood cell populations and therefore in their DNA; this may give incorrect genotyping results or prevent a conclusive result being issued. Clinical history of transplantation should be recorded on the request form.

Referring investigations

How to refer samples for investigation

IMPORTANT: Hospitals and reference centres wishing to refer for the first time must contact the Molecular Diagnostics laboratory in the first instance to discuss the appropriateness of the proposed investigation. Samples referred without the consent of the Molecular Diagnostics laboratory may not be investigated.