Genetic Characterisation of Human ABO Blood Group Variants with a Focus on Subgroups and Hybrid Alleles

University dissertation from Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University

Abstract: ABO is the most important blood group system in transfusion medicine and transplantation immunology. The ABO blood groups differ by the presence or absence of antigens on RBCs and antibodies in plasma. Accurate determination of ABO status is critical. Genomic typing can increase the precision of blood group determination in complicated cases, e.g. when variant expression of A or B antigen is encountered.

The overall aim of this study was to compare the molecular diversity of ABO alleles with various phenotypes, and to contribute to our knowledge of the ABO gene and encoded glycosyltransferases.

Novel alleles (six Aweak, eleven Bweak, seven O) were identified containing single-point mutations. Structure/function studies explained the weakening of some B subgroup glycosyltransferases. Two new hybrid Ax alleles were characterised. Analysis of introns 2-5 revealed 44 previously unknown, allele-related polymorphisms that proved valuable allelic markers. These findings enabled localisation of cross-over regions in two other new hybrids: 1) an O1v allele fused with an A2 allele, 2) the novel O1bantu-A2 combination that explained the Abantu phenotype. Phylogenetic and population analyses indicated that O1bantu is a unique and distinct evolutionary lineage so far only found among individuals of African descent.

Of clinical importance, a new approach to ABO genotyping was developed that identifies all common alleles, most null and weak A/B subgroups as well as hybrid alleles resulting from recombinational crossing-over events.

In summary, 30 novel alleles were identified and characterized, representing 30% of all alleles reported since the start of this study in 2001.