We aim to use UK Biobank’s whole genome sequencing data to discover the genomic determinants of clinically relevant antigen systems, with a focus on the ABO and Rh systems as well as additional genomic regions of immunological and clinical significance. Accurate antigen typing is essential for transfusion safety, transplantation compatibility, and other immune-related clinical applications. For blood typing, the current clinical standard serological methods are reliable for common antigens but lack scalability and can fail in contexts such as resolving rare alleles and ambiguous or weak antigen expression. Genomic approaches may provide the resolution and scalability needed for accurate antigen typing and also for mapping the broader genetic landscape of these clinically important immune-relevant loci.
Our objectives are:
1. Assembly of key loci – select reads and assemble genomic regions spanning the ABO and RHD/RHCE loci to resolve complex structural and sequence variation.
2. Variant discovery and curation – Identify single nucleotide and structural variants that determine antigenic status, including rare and novel alleles not represented in existing databases.
3. Panel development – Derive a set of target variants that can be used as a reference panel for molecular blood typing across diverse populations.
4. Extension to other loci – Apply and adapt these methods to additional blood group and immunologically important genomic regions, enabling broader insight into clinically relevant variation.
This framework will enable efficient, reproducible inference of antigenic profiles across large cohorts, potentially uncovering allelic diversity that serology alone cannot detect, supporting advances in transfusion medicine, immunogenetics, and precision-matching initiatives.