Molecular basis of Cromer blood group antigens

BACKGROUND: The Cromer blood group system consists of 10 antigens located o n decay-accelerating factor (DAF). Previous molecular genetic analysis has determined the basis for four of these antigens. The present study was unde rtaken to identify the mutations that determine the remaining antigens. STUDY DESIGN AND METHOD: Existing or new data were used to localize each Cr omer system antigen to a specific short consensus repeat (SCR) domain of DA F. The exon encoding that SCR domain was amplified by using the polymerase chain reaction (PCR) on genomic DNA obtained from individuals of that Crome r phenotype, and the DNA product was subjected to DNA sequence analysis. RESULTS: The TCa/TCc polymorphism is due to an R18P amino acid substitution in SCR1 of DAF. The Es(a+)/Es(a-) polymorphism is due to an I46N mutation in SCR1 of DAF. The WESb/WESa polymorphism is due to an L48R mutation in SC R1 of DAF. The UMC+/UMC-polymorphism is due to a T216M substitution in SCR4 of DAF. CONCLUSIONS: With information from previous reports and the findings of thi s study, the molecular genetic basis of all known alleles of the Cromer blo od group system has been elucidated. Single amino acid substitutions are re sponsible for 9 of the 10 antigens (all except the multiple-epitope antigen IFC).