Red cell genotyping

Red cell genotyping,^[1][2][3] also known as blood group genotyping,^[4][5][6][7] is a molecular technique used to identify genetic variants responsible for antigens on the surface of red blood cells.

Genotyping in transfusion medicine

Unlike traditional serological testing, which relies on the presence of antibodies to detect antigens, genotyping analyzes DNA to determine an individual's blood group profile with high accuracy. This approach is particularly valuable in complex transfusion cases, such as in patients with multiple alloantibodies, hemoglobinopathies, or recent transfusions that can obscure serological results. Red cell genotyping enhances transfusion safety by enabling precise donor-recipient matching, reducing the risk of alloimmunization, and improving outcomes for patients requiring chronic transfusions, such as sickle cell disease and thalassemia.

Red cell genotyping by real-time PCR: Duffy blood group system (FY) genotyping showing the melting peaks at 63°C for 3 homozygous Fy(a−b+) samples (orange), 69°C for 3 homozygous Fy(a+b−) samples (green), and 3 heterozygous Fy(a+b+) samples (blue).^[8]

The molecular testing of red cell antigens is often handled in conjunction with platelet and neutrophil antigens by professional organizations, such as the International Society of Blood Transfusion (ISBT)^[9] and the Association for the Advancement of Blood & Biotherapies (AABB).^[10]

Blood group genotyping versus Red cell genotyping

Blood group genotyping refers to the analysis of blood group antigens that are presented on the red cell membrane. These antigens are caused by

1. proteins integrated in the membrane,
2. carbohydrate components of glycoproteins and glycolipids,
3. proteins anchored via the Glycosylphosphatidylinositol (GPI)-linker,
4. variants of the GPI-linker itself.

As of June 2025, a total of 398 red cell antigens have been officially recognized by the ISBT.^[11] Of these, 371 antigens are organized into 48 distinct human blood group systems. The remaining 27 serologically-defined antigens have not yet been assigned to a blood group system. These include:

• The 200 series (the Collections) contains 9 antigens that are biochemically, genetically or serologically similar, but whose genetic basis has not yet been discovered.

• The 700 Series contains 16 antigens that do not fit into any system or collection and have an incidence of less than 1% across all human ethnic populations.

• The 901 Series contains 2 antigens that also cannot be included in any system or collection and have an incidence of more than 90% across all human ethnic populations.

Red cell genotyping is preferred over blood group genotyping because it includes all antigens found on the red cell membrane, not just those officially recognized as blood group antigens.

See also

• Blood type
• Blood transfusion
• Blood compatibility testing
• ABO blood group system
• Rh factor testing