Molecular Genetic Studies of the Blood Group ABO Locus in Man

University dissertation from Blood Centre, University Hospital, S-221 85 Lund, Sweden

Abstract: The ABO blood group system is undoubtedly the most important genetic and phenotypic marker in clinical transfusion medicine. The A and B determinants are immunodominant, terminally located carbohydrate residues of glycoconjugates on erythrocytes and other cell surfaces. The enzymes responsible for assembly of these structures are glycosyltransferases encoded by the ABO genes on chromosome nine. The aim of this study has been the molecular characterisation of alleles at the blood group ABO locus. Several previously unrecognised allelic forms have been described. During the study we have developed and validated clinically applicable DNA methods for the prediction of common and variant ABO phenotypes. The frequent occurrence of a variant O gene constituting an important polymorphic marker among blood group O individuals has been established. A molecular genetic basis for the Ael phenotype has been elucidated. The description of a DNA-based technique for detection of the Ael allele was the first reported for the molecular characterisation of an ABO subgroup. Phenotype-genotype correlations in A subgroups have been made and a suggested division into A1- and A2-allele-related weak subgroups of A has been put forward. Population studies of anthropological interest concerning the different ethnic groups in Brazil including the native Amazonian Indians exclusively expressing blood group O have been presented. The elusive complexity of human genome polymorphism has been exemplified by the unexpected finding of recombinational gene products in common ABO groups and also as a cause of the rare Ax subgroup. A relationship between the origin of these hybrid alleles and the occurrence of Chi-sequences, hotspots for bacterial recombination, in the ABO gene is proposed.

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