Sequence Analysis of the Spacer Region between the RHD and RHCE Genes

Abstract

Numerous variants of the Rh blood group system, discovered by Levine and Stetson in 1939, have been detected and more than forty antigens have been identified. By performing the molecular genetic analysis of the introns as well as the exons in both RH genes, it was elucidated that Rh variants were generated by gene conversion or recombination, deletions, or mutations. For understanding the generation of many Rh variants and Rh antigens in detail, it is necessary to analyze not only the RHCE and RHD genes but also the structure and the physical distance between both these RH genes. In order to achieve the aforesaid purpose, the spacer region between the RHD and RHCE genes were amplified by the long PCR method. Therefore the full spacer region was determined to be 12159 bp in length and contained the Alu consensus sequences and the putative CpG island. It was probable that the duplication of both RH genes occurred within about 12 kb region. Analysis of the spacer region provides new information for the research on the transcription-control region, the molecular evolution of RH genes, Rh variants, and the deletion of the RHD gene in Rh blood group system.