title: Mutations in GYPB exon 5 drive the S-s-U+(var) phenotype in persons of African descent: implications for transfusion.
abstract: BACKGROUND
  The S-s-U- phenotype in African Americans is due to a GYPB deletion, however the molecular basis for the S-s-U+var phenotype is poorly understood. Variable reactivity of S-s-U+var RBCs with monoclonal anti-He or by anti-U has been demonstrated, however the underlying molecular bases for this phenotype remain to be established.
  
  
  METHODS
  Hemagglutination was performed on 104 S-s- blood samples using monoclonal anti-He and anti-U. GYPB was sequenced from selected samples. Allele and exon-specific PCR analysis was used to identify wild-type and mutant alleles.
  
  
  RESULTS
  The RBCs of 49-percent S-s- samples were identified as S-s-U+var by hemagglutination. Sequencing analysis of 41 samples revealed 1) a point mutation at +5 (g > t) of intron 5 that resulted in skipping of exon 5 in 34 samples; 2) two mutations (208G > T and 230C > T) caused partial skipping of exon 5 in four samples due to activation of a cryptic 3' splice site that resulted from a C > G transversion at nt251 present in all GYPB*S alleles and most GYPB*s alleles tested. Three samples were heterozygous for the mutated alleles.
  
  
  CONCLUSIONS
  The S-s-U+var phenotype arises from changes in or around GYPB exon 5. The weak expression of U and in most examples, He, may be due to low levels of normal transcription of the variant gene or to posttranscriptional down regulation.
authors.affiliation: Immunohematology Laboratory, New York Blood Center, New York, New York 10021, USA.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Storry
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
authors.forename: Susan
authors.initials: S
authors.lastname: Fetics
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Huang
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D001803:Blood Transfusion; D005091:Exons; D006021:Glycophorins; D006801:Humans; D008951:MNSs Blood-Group System / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D012795:Sialoglycoproteins / Q000235:genetics*
chemical_list: C409973:GYPB protein, human; D006021:Glycophorins; D008951:MNSs Blood-Group System; D008562:Membrane Glycoproteins; D012795:Sialoglycoproteins