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Sequence-Based Typing of Human Blood Groups

In the last two decades, all but one of the genes encoding the 30 blood group systems present on red blood cells have been identified. This body of knowledge has permitted the application of molecular techniques to characterize the common blood group antigens and to elucidate the background for some of the variant phenotypes. DNA sequencing methodology was developed in the late 1970s and has become one of the most widely used techniques in molecular biology. In the field of immunohematology, this method is currently used by specialized laboratories to elucidate the molecular basis of unusual blood group phenotypes that cannot be defined by serology and genotyping. Because of the heterogeneity of the blood groups on both the antigen and the genetic level, special knowledge of the biology of blood group systems is needed to design sequencing strategies and interpret sequence data. This review summarizes the technical and immunohematologic expertise that is required when applying sequence-based typing for characterization of human blood groups.