title: Large deletions involving the regulatory upstream regions of A4GALT give rise to principally novel P1PK-null alleles.
abstract: BACKGROUND
  Cells of the clinically important p histo-blood group phenotype lack P1, P(k) , and P glycosphingolipid antigens. All cases investigated so far are due to alterations in the 4-α-galactosyltransferase-encoding Exon 3 of A4GALT. Repetitive elements in the genome can mediate DNA rearrangements, the most abundant being the Alu family of repeats.
  
  
  METHODS
  The aim of this study was to determine the genetic basis of three p samples with intact A4GALT open reading frames, using long-range polymerase chain reaction (PCR) and sequencing. In addition, transcript measurements were performed with quantitative PCR.
  
  
  RESULTS
  This is the first report of the p phenotype as the result of large deletions in A4GALT, comprising the proposed promoter and noncoding Exons 1 and 2a. The breakpoints were different in all three samples and revealed the presence of Alu or MIRb sequences directly flanking, or in close proximity to, all junctions. Furthermore, no A4GALT transcripts could be detected.
  
  
  CONCLUSIONS
  In summary, our data elucidate a new explanation underlying the p phenotype, implicating the deleted regions of A4GALT as crucial for P1 and P(k) synthesis, possibly due to loss of binding sites for erythroid transcription factors. Furthermore, analysis of these regions will improve genetic blood group prediction.
authors.affiliation: Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Westman
authors.forename: Asa
authors.initials: A
authors.lastname: Hellberg
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Britt
authors.initials: B
authors.lastname: Thuresson
authors.forename: Martin L
authors.initials: ML
authors.lastname: Olsson
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001789:Blood Group Antigens / Q000235:genetics; D005700:Galactosyltransferases / Q000235:genetics*; D017353:Gene Deletion; D005915:Globosides / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014281:Trihexosylceramides / Q000172:deficiency* / Q000235:genetics
chemical_list: D001789:Blood Group Antigens; D005915:Globosides; D014281:Trihexosylceramides; C480041:galactopyranosyl-1-4-paragloboside; C018549:globotriaosylceramide; D005700:Galactosyltransferases; C045097:UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase