Blood Group Genotyping

Red blood cell (RBC) antigens are inherited, intrinsic or adsorbed surface structures provoking specific humoral immune response. Historically, serologic—antibody-based and relatively unchanged since the early 20th century—assays imperfectly defined these antigens, at times hindering accurate phenotyping and compatible RBC transfusion and solid organ transplantation. Single-nucleotide variants (SNV), and less frequently structural variants, copy number variants or regulatory region variants encode RBC antigens. Whole genome, whole exome, and targeted next-generation sequencing (NGS) characterize these antigens more reliably and specifically than serology. Furthermore, long-reads, paired-end reads, split reads, and copy number analysis allow accurate prediction of challenging blood group systems including ABO, Rh, and MNS. NGS enriches analysis of challenging serologic cases by producing accurate phenotype data when blood samples are unobtainable, by screening the existing donor pool for rare blood identifying compatible blood for recipients via more rigorous standards and by preventing alloimmunization and hemolytic transfusion reactions. Similarly, recent array technology rapidly, accurately, inexpensively, and nearly exhaustively identifies known (and predicted) variants. Owing to significant time, cost, and clinical and research benefits, utilization of molecular RBC typing is expanding rapidly.