Red cell genotyping, also known as blood group genotyping, is a molecular technique used to identify genetic variants responsible for

antigens In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. An ...

on the surface of red blood cells.

Genotyping in transfusion medicine

Unlike traditional serological testing, which relies on the presence of

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

to detect

genotyping Genotyping is the process of determining differences in the genetic make-up (genotype) of an individual by examining the individual's DNA sequence using bioassay, biological assays and comparing it to another individual's sequence or a reference seq ...

analyzes

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

to determine an individual's

blood group A blood type (also known as a blood group) is based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycoli ...

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 Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility a ...

, and improving outcomes for patients requiring chronic transfusions, such as

sickle cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...

and

thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...

. The molecular testing of red cell antigens is often handled in conjunction with

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

and

neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...

antigens by professional organizations, such as the

International Society of Blood Transfusion The International Society of Blood Transfusion (ISBT) is a scientific society founded in 1935 which promotes the study of blood transfusion and provides information about the ways in which blood transfusion medicine and science can best serve p ...

(ISBT) and the Association for the Advancement of Blood & Biotherapies (

AABB AABB (Association for the Advancement of Blood & Biotherapies) is an international, not-for-profit organization representing individuals and institutions involved in the field of transfusion medicine and biotherapies. The association works coll ...

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 # proteins integrated in the membrane, # the carbohydrate components of

glycoproteins Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

and

glycolipids Glycolipids () are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the co ...

, # proteins anchored via the

Glycosylphosphatidylinositol Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide vari ...

(GPI)-linker, # variants of the GPI-linker itself. As of June 2025, a total of 398 red cell antigens have been officially recognized by the ISBT. Of these, 371 antigens are organized into 48 distinct

human blood group systems The term human blood group systems is defined by the International Society of Blood Transfusion (ISBT) as systems in the human species where cell-surface antigens—in particular, those on blood cells—are "controlled at a single gene locus or ...

. 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.

References

Blood Genetics Hematology Transfusion medicine Antigens {{improve categories, date=May 2025

Genotyping in transfusion medicine

Blood group genotyping versus Red cell genotyping

See also

References