Background: Only a few genetic variants have been reported in regulatory elements of blood group genes. Most of them affect GATA motifs, binding sites for the GATA-1 transcription factor.
Study design and methods: Samples from two patients and one donor with unusual or discrepant serology for ABO, RhD, and RhCE antigens were analyzed by DNA sequencing. Analyzed regions included the coding sequence and portions of regulatory elements. The effect of some variants on gene expression was evaluated in reporter gene assays.
Results: Three new alleles were identified. Their key variants are located in the ABO Intron 1 enhancer, the RHD proximal promoter, and the RHCE proximal promoter. IVS1 + 5859A was found in an African American patient with a group O forward type and a group B reverse type. 5'UTR-115C was the only RHD variant sequence found in a mixed-race black and Caucasian prenatal patient showing mixed-field agglutination with anti-D. 5'UTR-83T was found in several black donors and patients in the context of the genetically related RHCE*ceBI and RHCE*ceSM alleles. Reporter assays of promoter constructs including 5'UTR-115C or 5'UTR-83T showed a significant reduction in RH gene expression.
Conclusion: Three new alleles in the ABO, RHD, and RHCE genes consist of single-nucleotide changes within GATA motifs, emphasizing the key role of GATA transcription factors in the expression of blood group genes.
© 2017 AABB.