title: ABO transcript levels in peripheral blood and erythropoietic culture show different allele-related patterns independent of the CBF/NF-Y enhancer motif and multiple novel allele-specific variations in the 5'- and 3'-noncoding regions.
abstract: BACKGROUND
  Mechanisms regulating the ABO gene are unclear, especially in the hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding enhancer region is considered to have a major influence on transcription.
  
  
  METHODS
  Transcript levels in peripheral blood and in erythropoietic culture of CD34+ cells from marrow donors were measured with TaqMan assays. The 5'-regulatory region and 3'-downstream sequences were investigated to determine if allelic variations occur.
  
  
  RESULTS
  Surprisingly, transcripts from A(1) and A(2) alleles could not be detected in peripheral blood, although transcripts from B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb upstream and 1.8 kb downstream of the coding region showed multiple novel allele-specific and allele-related motifs. No correlation between these sequence variations and transcript levels was found, however. Contradictory to the results with peripheral blood, in erythropoietic culture of CD34+ cells from healthy marrow donors transcripts from A(1) and A(2) alleles were found at higher levels than transcripts from B/O(1)/O(1v) alleles.
  
  
  CONCLUSIONS
  These data do not support previous suggestions that nonsense-mutated O(1)/O(1v) transcripts are eliminated first. Furthermore, our results contradict the notion that the number of repeats in the upstream CBF/NF-Y-binding enhancer region, which contains four 43-bp repeats in A(2)/B/O(1)/O(1v) but only one 43-bp unit in A(1)/O(2) alleles, determines the transcription rate. The reason for the remarkable discrepancy between blood and marrow remains to be elucidated.
authors: Department of Laboratory Medicine, Lund University & Blood Center, Lund University Hospital, Lund, Sweden.
authors: Britt
authors: B
authors: Thuresson
authors: M Alan
authors: MA
authors: Chester
authors: Jill R
authors: JR
authors: Storry
authors: Martin L
authors: ML
authors: Olsson
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D018952:Antigens, CD34 / Q000097:blood; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism; D023081:CCAAT-Binding Factor / Q000235:genetics*; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014158:Transcription, Genetic
chemical_list: D000017:ABO Blood-Group System; D018952:Antigens, CD34; D023081:CCAAT-Binding Factor