Advancements in Blood Group Genotyping Technology and Clinical Applications

Blood group typing is essential in transfusion medicine, transplantation, and prenatal care. With the elucidation of the molecular genetics underlying blood group antigens, primarily single-nucleotide variants (SNVs), DNA-based genotyping has emerged as a powerful alternative to serological methods, enabling more accurate and comprehensive antigen prediction.

This review outlines the evolution of blood group genotyping technologies, structured around 2 main paradigms: targeted assays and comprehensive genomic approaches. Within targeted methods, throughput has progressed from low-throughput techniques (e.g., PCR-restriction fragment length polymorphism [PCR-RFLP]) to medium-throughput platforms (e.g., multiplex PCR with melting curve analysis) and high-throughput targeted solutions such as DNA microarrays. Comprehensive sequencing methods for high-resolution discovery, including Sanger sequencing, next-generation sequencing (NGS) and nanopore sequencing, enable unbiased, genome-wide antigen profiling. Together, these techniques allow for the detection of weak and variant antigens, the resolution of serological discrepancies, and high-resolution antigen profiling. This enables the identification of low-prevalence antigens as well as clinically significant high-prevalence antigen-negative phenotypes across ethnically diverse populations. We discuss the clinical and operational advantages of genotyping in complex scenarios such as alloimmunized patients and rare blood donor identification. Furthermore, applications extend beyond transfusion to organ transplantation and noninvasive prenatal testing for hemolytic disease of the fetus and newborn.

Molecular blood group genotyping offers a robust, scalable, and precise complement to serology. Integrating these technologies into routine practice enhances patient safety, optimizes blood inventory management, and contributes to broader insights into human genetic diversity. Continued technological advancements promise to further transform personalized transfusion strategies.