Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system
(2018) In Blood 132(3). p.334-338- 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 5 2.0 3 10222). The minor allele, rs311103C, disrupts... (More)
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 5 2.0 3 10222). 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(a2) 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 bioinformatic and molecular biological approach, we elucidated the underlying genetic basis for the last unresolved blood group system and made Xga genotyping possible.
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- author
- Möller, Mattias LU ; Lee, Yan Quan LU ; Vidovic, Karina LU ; Kjellström, Sven LU ; Björkman, Linda LU ; Storry, Jill R. LU and Olsson, Martin L. LU
- organization
- publishing date
- 2018-07-19
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 132
- issue
- 3
- pages
- 5 pages
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:29748255
- scopus:85050133445
- ISSN
- 0006-4971
- DOI
- 10.1182/blood-2018-03-842542
- project
- Bioinformatic Analysis of Blood Group Genomics
- language
- English
- LU publication?
- yes
- id
- 17f6396c-7c20-4ae8-9717-945a84f216d1
- date added to LUP
- 2018-08-21 11:12:58
- date last changed
- 2024-09-17 01:21:23
@article{17f6396c-7c20-4ae8-9717-945a84f216d1, abstract = {{<p>The Xg<sup>a</sup> blood group is differentially expressed on erythrocytes from men and women. The underlying gene, PBDX, was identified in 1994, but the molecular background for Xg<sup>a</sup> 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 Xg<sup>a</sup> 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 5 2.0 3 102<sup>22</sup>). 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(a2) 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 bioinformatic and molecular biological approach, we elucidated the underlying genetic basis for the last unresolved blood group system and made Xg<sup>a</sup> genotyping possible.</p>}}, author = {{Möller, Mattias and Lee, Yan Quan and Vidovic, Karina and Kjellström, Sven and Björkman, Linda and Storry, Jill R. and Olsson, Martin L.}}, issn = {{0006-4971}}, language = {{eng}}, month = {{07}}, number = {{3}}, pages = {{334--338}}, publisher = {{American Society of Hematology}}, series = {{Blood}}, title = {{Disruption of a GATA1-binding motif upstream of<i> XG</i>/<i>PBDX</i> abolishes Xg<sup>a</sup> expression and resolves the Xg blood group system}}, url = {{http://dx.doi.org/10.1182/blood-2018-03-842542}}, doi = {{10.1182/blood-2018-03-842542}}, volume = {{132}}, year = {{2018}}, }