title: Weak blood group B phenotypes may be caused by variations in the CCAAT-binding factor/NF-Y enhancer region of the ABO gene.
abstract: BACKGROUND
  Binding of CCAAT-binding factor NF-Y (CBF/NF-Y) to a 43-bp repeat unit in the minisatellite region in the 5' region of the ABO gene (CBF/NF-Y enhancer region) plays an important role in regulating the transcription of ABO genes. The common ABO alleles were found to have CBF/NF-Y enhancer regions with specific numbers of 43-bp minisatellite repeats.
  
  
  METHODS
  Blood samples from four healthy blood donors with weak B phenotypes were subjected to extensive ABO genotyping, including nucleotide sequencing of the 5' regulatory region containing the CBF/NF-Y enhancer.
  
  
  RESULTS
  The coding region of the ABO genes exhibited common ABO*B101-heterozygous genotypes in all samples, but unexpected variations were observed in the CBF/NF-Y enhancer region. In two cases, the CBF/NF-Y enhancer motifs did not exhibit the expected ABO allele dependency. One, an AB(weak) sample was heterozygous for ABO*A101 and ABO*B101 but homozygous for the ABO*B101-specific CBF/NF-Y motif. The second had a common ABO*B101/ABO*O01 genotype but was heterozygous for ABO*A101- and ABO*O01-specific enhancer motifs. In the other two samples, novel CBF/NF-Y motifs were found. One contained a shortened version of an otherwise ABO*B101-specific CBF/NF-Y motif, and the other had a single-base substitution located 12 bp upstream from the beginning of the first 43-bp repeat of an ABO*B101-specific CBF/NF-Y enhancer sequence.
  
  
  CONCLUSIONS
  The frequency of variations in the CBF/NF-Y region of the ABO gene in these samples with presumably common ABO*B101 alleles suggests that weak blood group B phenotypes may be caused by sequence variations in the CBF/NF-Y regulatory region.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Seltsam
authors.forename: Franz F
authors.initials: FF
authors.lastname: Wagner
authors.forename: Daniela
authors.initials: D
authors.lastname: Grüger
authors.forename: Christa D
authors.initials: CD
authors.lastname: Gupta
authors.forename: Christina
authors.initials: C
authors.lastname: Bade-Doeding
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D000017:ABO Blood-Group System; D023081:CCAAT-Binding Factor