title: Disruption of SMIM1 causes the Vel- blood type.
abstract: Here, we report the biochemical and genetic basis of the Vel blood group antigen, which has been a vexing mystery for decades, especially as anti-Vel regularly causes severe haemolytic transfusion reactions. The protein carrying the Vel blood group antigen was biochemically purified from red blood cell membranes. Mass spectrometry-based de novo peptide sequencing identified this protein to be small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. Expression of SMIM1 cDNA in Vel- cultured cells generated anti-Vel cell surface reactivity, confirming that SMIM1 encoded the Vel blood group antigen. A cohort of 70 Vel- individuals was found to be uniformly homozygous for a 17 nucleotide deletion in the coding sequence of SMIM1. The genetic homogeneity of the Vel- blood type, likely having a common origin, facilitated the development of two highly specific DNA-based tests for rapid Vel genotyping, which can be easily integrated into blood group genotyping platforms. These results answer a 60-year-old riddle and provide tools of immediate assistance to all clinicians involved in the care of Vel- patients.
authors.affiliation: Department of Biology, University of Vermont, Burlington, VT, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.forename: Virginie
authors.initials: V
authors.lastname: Helias
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Cécile
authors.initials: C
authors.lastname: Menanteau
authors.forename: Carole
authors.initials: C
authors.lastname: Saison
authors.forename: Nicole
authors.initials: N
authors.lastname: Lucien
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bourgouin
authors.forename: Maude
authors.initials: M
authors.lastname: Le Gall
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
mesh_terms: D000595:Amino Acid Sequence; D001789:Blood Group Antigens / Q000235:genetics / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D017353:Gene Deletion; D008040:Genetic Linkage; D005838:Genotype; D006720:Homozygote; D006801:Humans; D020014:K562 Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D053719:Tandem Mass Spectrometry; D014162:Transfection
chemical_list: D001789:Blood Group Antigens; D008565:Membrane Proteins; C584052:SMIM1 protein, human