Abstract

BACKGROUND AND OBJECTIVES:

5'-flanking sequences of the ABO gene play important role in the regulation of gene expression, but polymorphism of 5'-flanking sequence of ABO gene is rarely known. Here, we further characterize the molecular genetic basis and ABO allele-related polymorphism of the 5'-untranslated regions (5'-UTR) of the human ABO gene.

MATERIALS AND METHODS:

Collecting blood samples from 72 blood donors in Hangzhou, China, we analysed sequences of exons 6 and 7 of ABO gene and amplified an enhanced segment of 43 bp repeats in the 5'-UTR. Subsequently, we selected 25 homozygotes [of genotypes A101/A101 (two), A102/A102 (seven), B101/B101 (seven) and O01/O01 (nine)] and five heterozygotes [A102/O01 (two), B101/O01 (two) and O01/O105 (one)] for sequencing 5 -kb amplicons spanning the 5'-UTR and partial exon 1 of the ABO gene. We sequenced the amplicons bidirectionally and, when pertinent, analysed selected haplotypes by cloning.

RESULTS:

As a result, we identified 11 new polymorphic sites (10 point mutations, one 8-bp deletion) in the 5'-UTR of the A102, B101 and O01 alleles of common ABO phenotypes. Five A102 alleles carry four tandem repeats of a 43-bp minisatellite unit that deviated from previous reports.

CONCLUSION:

The results revealed the DNA polymorphisms in the 5'-UTRs correlated with the common ABO alleles. Elucidation of the diversity of the 5'-UTRs is an important supplement to existing methods for increasing our understanding of the molecular basis of the ABO blood group system.