LAUSR

Red blood cell (RBC) antigen typing of both recipients and donors is vital for safe and effective transfusion. Despite the existence of >330 RBC antigens, current routine pre-transfusion testing only includes matching the patient and donor for ABO and D, since serologic typing methods are difficult to scale for routine non-ABO/D antigen typing (i.e., extended antigen typing). While PCR-based genotyping can be used to broadly genotype most antigens, current assay formats limit the number of genetic changes and samples that can be simultaneously tested (~50 genetic changes and ~100 samples per run). However, the emergence of RBC antigen genotyping using next-generation sequencing (NGS) and high-density DNA arrays have the potential to overcome many of these limitations. NGS allows an unprecedented evaluation of genetic changes including novel genetic changes and complex structural variations (SVs), representing the new gold standard for RBC antigen genotyping. High-density DNA arrays allow for low cost evaluation of all known genetic changes including SV with the ability to run 1,000s of samples at a time. As such, NGS will likely replace conventional PCR genotyping for discordants and complex serologic workups and offer an unprecedented level of discovery for new RBC antigens. High-density DNA arrays have the potential to allow for routine genotyping of all blood donors for all genetically understood antigens, something that will fundamentally change the practice of transfusion medicine.