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Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype.

Storry, Jill LU ; Jöud, Magnus LU orcid ; Christophersen, Mikael Kronborg LU ; Thuresson, Britt LU ; Åkerström, Bo LU ; Sojka, Birgitta Nilsson ; Nilsson, Björn LU and Olsson, Martin L LU orcid (2013) In Nature Genetics 45(5). p.109-537
Abstract
The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and... (More)
The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and SMIM1 overexpression induced Vel expression. Genotype screening estimated that ∼1 of 17 Swedish blood donors is a heterozygous deletion carrier and ∼1 of 1,200 is a homozygous deletion knockout and enabled identification of Vel-negative donors. Our results establish SMIM1 as a new erythroid gene and Vel as a new blood group system. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
45
issue
5
pages
109 - 537
publisher
Nature Publishing Group
external identifiers
  • wos:000318158200017
  • pmid:23563606
  • scopus:84878603453
  • pmid:23563606
ISSN
1546-1718
DOI
10.1038/ng.2600
project
Genetic variation exposes regulators of blood cell formation in vivo in humans
language
English
LU publication?
yes
id
fedf508c-3fb5-415e-a80c-a6347ec371ac (old id 3734051)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23563606?dopt=Abstract
date added to LUP
2016-04-01 10:55:58
date last changed
2023-01-02 17:11:40
@article{fedf508c-3fb5-415e-a80c-a6347ec371ac,
  abstract     = {{The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and SMIM1 overexpression induced Vel expression. Genotype screening estimated that ∼1 of 17 Swedish blood donors is a heterozygous deletion carrier and ∼1 of 1,200 is a homozygous deletion knockout and enabled identification of Vel-negative donors. Our results establish SMIM1 as a new erythroid gene and Vel as a new blood group system.}},
  author       = {{Storry, Jill and Jöud, Magnus and Christophersen, Mikael Kronborg and Thuresson, Britt and Åkerström, Bo and Sojka, Birgitta Nilsson and Nilsson, Björn and Olsson, Martin L}},
  issn         = {{1546-1718}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{109--537}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype.}},
  url          = {{https://lup.lub.lu.se/search/files/2251650/4139376.pdf}},
  doi          = {{10.1038/ng.2600}},
  volume       = {{45}},
  year         = {{2013}},
}