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Large deletions involving the regulatory upstream regions of A 4 GALT give rise to principally novel P 1 PK ‐null alleles
Author(s) -
Westman Julia S.,
Hellberg Åsa,
Peyrard Thierry,
Thuresson Britt,
Olsson Martin L.
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12543
Subject(s) - allele , genetics , biology , chemistry , gene
Background Cells of the clinically important p histo‐blood group phenotype lack P 1, P k , and P glycosphingolipid antigens. All cases investigated so far are due to alterations in the 4‐α‐galactosyltransferase‐encoding E xon 3 of A 4 GALT . Repetitive elements in the genome can mediate DNA rearrangements, the most abundant being the A lu family of repeats. Study Design and Methods The aim of this study was to determine the genetic basis of three p samples with intact A 4 GALT 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 A 4 GALT , comprising the proposed promoter and noncoding E xons 1 and 2a. The breakpoints were different in all three samples and revealed the presence of A lu or MIRb sequences directly flanking, or in close proximity to, all junctions. Furthermore, no A 4 GALT transcripts could be detected. Conclusion In summary, our data elucidate a new explanation underlying the p phenotype, implicating the deleted regions of A 4 GALT as crucial for P 1 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.