Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system.

Blood
Mattias MöllerMartin L Olsson

Abstract

The Xga blood group is differentially expressed on erythrocytes from men and women. The underlying gene, PBDX, was identified in 1994, but the molecular background for Xga expression remains undefined. This gene, now designated XG, partly resides in pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome. By comparing calculated Xga allele frequencies in different populations with 2612 genetic variants in the XG region, rs311103 showed the strongest correlation to the expected distribution. The same single-nucleotide polymorphism (SNP) had the most significant impact on XG transcript levels in whole blood (P = 2.0 × 10-22). The minor allele, rs311103C, disrupts a GATA-binding motif 3.7 kb upstream of the transcription start point. This silences erythroid XG messenger RNA expression and causes the Xg(a-) phenotype, a finding corroborated by SNP genotyping in 158 blood donors. Binding of GATA1 to biotinylated oligonucleotide probes with rs311103G but not rs311103C was observed by electrophoretic mobility shift assay and proven by mass spectrometry. Finally, a luciferase reporter assay indicated this GATA motif to be active for rs311103G but not rs311103C in HEL cells. By using an integrated bioinf...Continue Reading

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Citations

Aug 9, 2019·Transfusion·William J LaneUNKNOWN MilSeq Project
Sep 7, 2019·Current Opinion in Hematology·Celina MontemayorMargaret A Keller
Jul 22, 2018·Blood·Peter A Zimmerman
Feb 28, 2019·Frontiers in Physiology·Gloria BarbaraniAntonella E Ronchi
Apr 20, 2021·PLoS Genetics·Bruno MonteiroAntónio Amorim
May 8, 2021·Journal of Proteome Research·Flora CozzolinoMaria Monti
May 23, 2021·Clinical and Experimental Immunology·Zhaohu YuanXuexin Yang
Jul 3, 2021·Investigational New Drugs·Ean-Jeong SeoThomas Efferth
Feb 29, 2020·Transfusion Medicine and Hemotherapy : Offizielles Organ Der Deutschen Gesellschaft Fur̈ Transfusionsmedizin Und Immunham̈atologie·Yann FichouClaude Férec

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