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.
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 .
Which gene-defect causes the Vel-blood type?
Which gene - defect causes the Vel - blood type ?
a 17 nucleotide deletion
a 17 nucleotide deletion