Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3734051
- author
- Storry, Jill LU ; Jöud, Magnus LU ; Christophersen, Mikael Kronborg LU ; Thuresson, Britt LU ; Åkerström, Bo LU ; Sojka, Birgitta Nilsson ; Nilsson, Björn LU and Olsson, Martin L LU
- organization
- publishing date
- 2013
- 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}}, }