Researchers have identified the molecular basis of the Vel antigen. This work establishes the gene encoding the small integral membrane protein 1, or SMIM1, as a new erythroid gene in which a deletion defines the Vel-negative blood group phenotype.
The Vel-negative blood group phenotype was first described in 1952, after Mrs. Vel had an acute hemolytic transfusion reaction. However, until now, the genetic basis of this phenotype had remained unknown, and transfusion services have had difficulty finding compatible blood for Vel-negative patients.
Here is Dr. Connie Westhoff of the New York Blood Center:
“Three research groups have been working on finding the carrier of this blood group antigen, and this amazing race for the Vel antigen has been notoriously difficult with several dead ends and misleading clues. And we here at The New York blood center and we have been screening for Vel- since the 1970’s and we have seen over 60 patients or donors, but we’ve always been somewhat perplexed that many were not compatible with each other.”
Dr. Jill Storry, of Lund University, led one of these three research groups. Here is Dr. Storry:
“This project is the culmination of perhaps 10 years of research working to try and identify the molecular carrier Vel-blood group antigen which, as you know, is a very clinically important antigen.”
Dr. Storry and colleagues were able to identify a common deletion across 20 Vel-negative individuals on chromosome 1, and ultimately identified SMIM1 as the erythroid gene encoding a conserved transmembrane protein.
Here again, is Dr. Storry: “We identified a 17 base pair deletion in the coding region of that gene and interestingly in the samples that we’ve sequenced all the Vel-negative people have this particular molecular background. And that was essentially an inactivating mutation in this gene.”
Dr. Westhoff commented on the implications of these findings:
“Now with this finding we can significantly narrow our search for compatible blood, and importantly, greatly improve patient care with the discovery of both the gene and now we have the ability to test for Vel by DNA methods. “
With this evidence, the International Society of Blood Transfusion has provisionally designated Vel as a new blood group system.
We’ll be back on June 15th with another edition of Transfusion News. Thanks for joining us.
1. Storry JR, Joud M, Christophersen MK, Thuresson B, Akerstrom B, Sojka BN, Nilsson B, Olsson ML. Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype. Nat Genet 2013;45: 537-41.
2. Cvejic A, Haer-Wigman L, Stephens JC, Kostadima M, Smethurst PA, Frontini M, van den Akker E, Bertone P, Bielczyk-Maczynska E, Farrow S, Fehrmann RS, Gray A, de Haas M, Haver VG, Jordan G, Karjalainen J, Kerstens HH, Kiddle G, Lloyd-Jones H, Needs M, Poole J, Soussan AA, Rendon A, Rieneck K, Sambrook JG, Schepers H, Sillje HH, Sipos B, Swinkels D, Tamuri AU, Verweij N, Watkins NA, Westra HJ, Stemple D, Franke L, Soranzo N, Stunnenberg HG, Goldman N, van der Harst P, van der Schoot CE, Ouwehand WH, Albers CA. SMIM1 underlies the Vel blood group and influences red blood cell traits. Nat Genet 2013;45: 542-5.
3. Ballif BA, Helias V, Peyrard T, Menanteau C, Saison C, Lucien N, Bourgouin S, Le Gall M, Cartron JP, Arnaud L. Disruption of SMIM1 causes the Vel- blood type. EMBO Mol Med 2013;5:751-761.