Characterisation of weak and null phenotypes in the KEL and JK blood group systems

The focus of this thesis is on KEL and JK, two clinically important blood group systems, and the investigations of blood samples with aberrant antigen expression as in null and weak phenotypes, or with a phenotype that does not correspond to genotype. With the increasing use of DNA assays based on single nucleotide polymorphisms for blood group prediction, it is important to characterize the blood-groupencoding genes. Otherwise, when using these assays for phenotype prediction, tests risk giving rise to false results if null or otherwise altered genes are present and the test are not designed to take alterations into consideration. This is especially applicable for foetal blood group prediction, finding matching blood donors to transfusion-dependent patients or to correctly type multi-transfused patients where serology is inadequate. For each blood group system investigated here, four novel null alleles and one allele giving rise to weak antigen expression were characterised. Most importantly, a novel Jk(a+w) phenotype was described and associated with a novel JK*01M allele. A control cohort was screened for the associated polymorphism and allele frequencies calculated. A simple PCR-ASP method for screening of five null alleles giving rise to the Jk(a–b–) phenotype was devised, utilised and proven useful. In summary, this thesis contributes to the overall understanding of the molecular genetic basis of human blood group diversity in the two investigated systems and the results will improve the prediction of blood group phenotypes from DNA-based assays