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Nat Genet. 2013 May;45(5):542-545. doi: 10.1038/ng.2603. Epub 2013 Apr 7.

SMIM1 underlies the Vel blood group and influences red blood cell traits.

Author information

1
Department of Haematology, University of Cambridge, CB2 0PT, United Kingdom.
2
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1HH, United Kingdom.
3
Department of Experimental Immunohaematology, Sanquin Research, 1066 CX, Amsterdam, The Netherlands.
4
Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, 1066 CX, The Netherlands.
5
NIHR Cambridge Biomedical Research Centre, Cambridge, CB2 0QQ, United Kingdom.
6
NHS Blood and Transplant, Cambridge, CB2 0PT, United Kingdom.
7
EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom.
8
Department of Hematopoiesis, Sanquin Research, Amsterdam, 1066 CX, The Netherlands.
9
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700 RB, The Netherlands.
10
NHS Blood and Transplant, Tooting, London, SW17 0RB, United Kingdom.
11
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700 RB, The Netherlands.
12
Somerville, Massachusetts, USA.
13
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, 6525 GA, The Netherlands.
14
International Blood Group Reference Laboratory, NHS Blood and Transplant, North Bristol Park, Northway, Filton, Bristol, BS34 7QH, United Kingdom.
15
MRC Biostatistics Unit, Institute of Public Health, Cambridge, CB2 0SR, United Kingdom.
16
Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, DK-2100, Denmark.
17
University of Groningen, University Medical Center Groningen, Department of Experimental Hematology, Groningen, 9700 RB, The Netherlands.
18
University of Groningen, University Medical Center Groningen, Department of Stem Cell Biology, Groningen, 9700 RB, The Netherlands.
19
Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic diseases, Radboud University Medical Centre, Nijmegen, 6500 HB, The Netherlands.
20
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, 6500 HB, The Netherlands.
#
Contributed equally

Abstract

The blood group Vel was discovered 60 years ago, but the underlying gene is unknown. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel. To identify the responsible gene, we sequenced the exomes of five individuals negative for the Vel antigen and found that four were homozygous and one was heterozygous for a low-frequency 17-nucleotide frameshift deletion in the gene encoding the 78-amino-acid transmembrane protein SMIM1. A follow-up study showing that 59 of 64 Vel-negative individuals were homozygous for the same deletion and expression of the Vel antigen on SMIM1-transfected cells confirm SMIM1 as the gene underlying the Vel blood group. An expression quantitative trait locus (eQTL), the common SNP rs1175550 contributes to variable expression of the Vel antigen (P = 0.003) and influences the mean hemoglobin concentration of red blood cells (RBCs; P = 8.6 × 10(-15)). In vivo, zebrafish with smim1 knockdown showed a mild reduction in the number of RBCs, identifying SMIM1 as a new regulator of RBC formation. Our findings are of immediate relevance, as the homozygous presence of the deletion allows the unequivocal identification of Vel-negative blood donors.

PMID:
23563608
PMCID:
PMC4179282
DOI:
10.1038/ng.2603
[Indexed for MEDLINE]
Free PMC Article

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