title: Impact of genetic variation in the SMIM1 gene on Vel expression levels.
abstract: BACKGROUND
  Serologic determination of the Vel- phenotype is challenging due to variable Vel expression levels. In this study we investigated the genetic basis for weak Vel expression levels and developed a high-throughput genotyping assay to detect Vel- donors.
  
  
  METHODS
  In 548 random Caucasian and 107 Vel+(w) donors genetic variation in the SMIM1 gene was studied and correlated to Vel expression levels. A total of 3366 Caucasian, 621 black, and 333 Chinese donors were screened with a high-throughput genotyping assay targeting the SMIM1*64_80del allele.
  
  
  RESULTS
  The Vel+(w) phenotype is in most cases caused by the presence of one SMIM1 allele carrying the major allele of the rs1175550 SNP in combination with a SMIM1*64_80del allele or in few cases caused by the presence of the SMIM1*152T>A or SMIM1*152T>G allele. In approximately 6% of Vel+(w) donors genetic factors in SMIM1 could not explain the weak expression. We excluded the possibility that lack of expression of another blood group system was correlated with weak Vel expression levels. Furthermore, using a high-throughput Vel genotyping assay we detected two Caucasian Vel- donors.
  
  
  CONCLUSIONS
  Weak Vel expression levels are caused by multiple genetic factors in SMIM1 and probably also by other genetic or environmental factors. Due to the variation in Vel expression levels, serologic determination of the Vel- phenotype is difficult and a genotyping assay targeting the c.64_80del deletion in SMIM1 should be used to screen donors for the Vel- phenotype.
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Lonneke
authors: L
authors: Haer-Wigman
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Tamara C
authors: TC
authors: Stegmann
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Shabnam
authors: S
authors: Solati
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Aïcha
authors: A
authors: Ait Soussan
authors: Maastricht University Medical Center, Maastricht, the Netherlands.
authors: Erik
authors: E
authors: Beckers
authors: Department of Cardiology & Department of Genetics.
authors: Pim
authors: P
authors: van der Harst
authors: Department of Stem Cell Biology & Department of Experimental Hematology, Sanquin Diagnostic Services, Amsterdam, the Netherlands.
authors: Marga
authors: M
authors: van Hulst-Sundermeijer
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Peter
authors: P
authors: Ligthart
authors: Sanquin Blood Bank, Rotterdam, the, Netherlands.
authors: Dick
authors: D
authors: van Rhenen
authors: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors: Hein
authors: H
authors: Schepers
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Masja
authors: M
authors: de Haas
authors: Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: C Ellen
authors: CE
authors: van der Schoot
mesh_terms: D000483:Alleles; D001782:Blood Donors / Q000706:statistics & numerical data; D001789:Blood Group Antigens / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D001789:Blood Group Antigens; D008565:Membrane Proteins; C584052:SMIM1 protein, human