SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression
(2017) In Scientific Reports 7.- Abstract
The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a... (More)
The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing.
(Less)
- author
- Christophersen, Mikael K.
LU
; Jöud, Magnus
LU
; Ajore, Ram LU ; Vege, Sunitha ; WICKELGREN LJUNGDAHL, KLARA LU ; Westhoff, Connie M ; Olsson, Martin L. LU
; Storry, Jill R. LU and Nilsson, Björn LU
- organization
- publishing date
- 2017-01-13
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- article number
- 40451
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85009518349
- pmid:28084402
- wos:000391927600001
- ISSN
- 2045-2322
- DOI
- 10.1038/srep40451
- project
- Genetic variation exposes regulators of blood cell formation in vivo in humans
- language
- English
- LU publication?
- yes
- id
- 87a03bc9-14d0-41e0-a552-b52b3fc573a8
- date added to LUP
- 2017-02-28 12:09:43
- date last changed
- 2025-01-07 08:40:07
@article{87a03bc9-14d0-41e0-a552-b52b3fc573a8, abstract = {{<p>The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing.</p>}}, author = {{Christophersen, Mikael K. and Jöud, Magnus and Ajore, Ram and Vege, Sunitha and WICKELGREN LJUNGDAHL, KLARA and Westhoff, Connie M and Olsson, Martin L. and Storry, Jill R. and Nilsson, Björn}}, issn = {{2045-2322}}, language = {{eng}}, month = {{01}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression}}, url = {{http://dx.doi.org/10.1038/srep40451}}, doi = {{10.1038/srep40451}}, volume = {{7}}, year = {{2017}}, }