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, 17 (3), 217-222

Molecular Genetic Analysis of Weak ABO Subgroups in the Chinese Population Reveals Ten Novel ABO Subgroup Alleles

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Molecular Genetic Analysis of Weak ABO Subgroups in the Chinese Population Reveals Ten Novel ABO Subgroup Alleles

Haobo Huang et al. Blood Transfus.

Abstract

Background: A weak ABO subgroup is one of the most important causes of an ABO blood grouping discrepancy. Here, we investigated the distribution of weak ABO subgroups in the Chinese population and identified ten novel weak ABO subgroup alleles.

Material and methods: We performed phenotype investigations by serological studies, analysed the DNA sequence of the ABO gene by direct sequencing or sequencing after cloning, and evaluated the role of glycosyltransferase mutations by in silico analysis and in vitro expression assay.

Results: Three hundred and fifty-one individuals with a weak ABO subgroup were detected among 1.45 million blood-typed subjects. Ten novel weak ABO subgroup alleles were identified. Molecular modelling and analysis of GTA mutation p.L339P suggested that the mutation may change the local conformation of GTA and reduce its stability. The in vitro expression assay showed that A antigen expression and agglutination of HeLa cells transfected with GTA mutant p.L339P decreased significantly compared to those of cells transfected with wild-type GTA.

Conclusion: Ten novel weak ABO subgroup alleles were identified in the Chinese population. GTA mutant p.L339P may lead to a weak A phenotype by changing the local conformation of GTA and reducing its stability.

Figures

Figure 1
Figure 1
p.L339P in GTA was predicted to destroy a local hydrogen-bond framework. (A) Ribbon drawing of the overall GTA structure showing the site of the p.L339P mutation. (B) The local residues are represented by balls and sticks. O, C, N, and H atoms are represented by red, bluish green, blue and grey balls, respectively. The red dotted line indicates a hydrogen bond. In the wild-type GTA, a hydrogen bond framework was formed by L339.O-R217.C, L339.O- H2O-R217.C and L339.N-H2O-D218.O. (C) In the GTA p.L339P mutant, the former hydrogen bond framework disappeared and two new hydrogen bonds were formed between P339.O-H2O-D218.O.
Figure 2
Figure 2
In vitro expression studies showed that the p.L339P substitution affects A antigen expression. (A) The median fluorescence index (MFI) of HeLa cells after transfection with wild-type GTA, the p.L339P mutant, or a control construct. (B) The relative percentage of antigen-expressing cells (AEC%) of HeLa cells after transfection with wild-type GTA, the p.L339P mutant, or a control construct. (C–E), The transfected HeLa cells were incubated with anti-A antibody and cell agglutination was observed using a phase contrast microscope. The aggregation of cells transfected with the mutant p.L339P construct (C), a control construct (D), or wild-type GTA construct (E) is shown.

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