Correlation Between Phenotype and Genotype in Some Clinically Important Blood group Systems

University dissertation from Depatment of Transfusion Medicne

Abstract: In the past decade, the molecular basis for most of the blood group systems has been investigated intensively. Many blood group genes have been cloned and the polymorphisms of clinically significant blood group systems have been elucidated. The aim of this study was to investigate the molecular genetic variation found in various phenotypes and in different ethnic populations, to identify new alleles, to try to understand how they contribute to the different phenotypes and to improve current DNA-based blood grouping methods for use in transfusion medicine. A single-tube PCR-ASP method for JK blood group determination was developed for clinical use. The genomic organisation of the JK blood group locus was characterised and the molecular basis of the Jk(a-b-) phenotype associated with the absence of the urea transporter JK glycoprotein in erythrocytes was elucidated in different ethnic groups. A DNA-based method was designed for detection of silent Jk alleles at the JK locus. The relationship between the ABO alleles and the number of tandem repeats in a potential enhancer region that contains a transcription factor-binding motif was defined. A large collection of clinical samples with serological ABO discrepancies was screened for known allelic variations. Analysis of genomic DNA of all exons and two regulatory regions of the ABO gene revealed fifteen novel A and B alleles that were associated with A and B subgroups. Finally, the phenotype/genotype correlation for clinically significant blood group systems in Jordanian blood donors was studied for the first time to investigate the reliability of current genotyping methods in populations of Arabian descent. The correlation was high, similar to that found in Caucasians. In conclusion, our knowledge of the alleles responsible for different blood group phenotypes has been increased, which has resulted in improved clinical genotyping methods.

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