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Blood group genotyping goes next generation: featuring ABO, RH and MNS

There are currently 36 blood group systems comprising over 300 antigens. The genomic backgrounds of polymorphisms responsible for antigens of each blood group have been established. Current blood group genotyping platforms are focused on testing for antigen‐determine single nucleotide polymorphisms, which are the differences on DNA level for predicting the antigen phenotype, and thus are faced with challenges because of lack of ability to detect unknown variants, structural variants and copy number variations. With the advances in technology and bioinformatics analyses, next‐generation sequencing (NGS) is now an applicable platform for high‐throughput, accurate and extensive blood group genotyping. The widely used platforms and processing steps of NGS are illustrated in this article, as well as an overview of published works. NGS has been used in various applications involving blood group genomics, including location of genetic variants for blood group expression, antenatal care, allele frequency estimation and blood group antigen prediction. Even for some of the most complicated blood group systems, NGS provides insight to solve cis/trans associations and gene rearrangements occurring in homologous genes, as featured for the ABO, RH and MNS systems in this review. Although certain issues such as cost, turnaround time, secured data storage and verification remain challenges for routine blood group genotyping practices, NGS still holds great promise advancement in future perspectives.