Transcription starting from an alternative promoter leads to the expression of the human ABO histo‐blood group antigen

Abstract

This study suggests that a functional A transferase could be produced by the transcription from exon 1a.

A weak blood group A phenotype caused by a translation‐initiator mutation in the ABO gene

“…Because ABO sequence analysis in the donor samples was only performed on the genomic DNA level and the N‐terminus of the encoded A transferase was not examined in the propositus and his daughter, it cannot be excluded that the translation‐initiator mutation resulted in a N‐terminally expanded A transferase driven by an alternative upstream start site. The good correlation between the results of the expression study, however, and the in vivo findings as well as the fact that there is so far only evidence for one alternative starting exon at the ABO locus, which, in addition, does not contain ATG codons, 12 indicate that alternative downstream start sites are the most probable molecular mechanism of the weakened A antigen expression in our A weak B donor.…”

“…The locations of putative initiator methionine codons at AAs 1, 20, 26, 43, 53, 69, 142, 186, 189, 191, 214, 288, and 289 are indicated by arrows if based on a Kozak consensus nt sequence context and by open triangles if not. 12 Exons 1 through 7 of the ABO gene are aligned in the diagram below the schematic representation of ABO transferase.…”

The Abantu phenotype in the ABO blood group system is due to a splice‐site mutation in a hybrid between a new O1‐like allelic lineage and the A2 allele

“…Therefore, it appears incapable of producing expression of even the weak A antigen on RBCs reported to be consistently inherited from one generation to the other among A bantu individuals [7]. Recent work has indicated the possibility of downstream translation start codons (at residues 26, 53 and 69) that are capable of producing proteins with some enzyme activity [22], although there is still no proof of such N‐terminally truncated proteins actually existing in vivo . Furthermore, the last one of these methionine codons is the only one that would not be abolished by the frameshift caused by the exon 4/intron 4 guanosine deletion, and it is somewhat unclear whether the transfection of MKN28 cells with a construct starting at Met69 retained any clinically relevant enzymatic activity in the in vitro experiments reported previously [22].…”

Identification and characterization of a novel antisense RNA transcribed from the opposite strand of the human blood group ABO gene

“…A and B antigens are biosynthesized by A and B transferases encoded by the A and B genes, respectively, at the ABO locus in the long arm of chromosome 9 1 . Since clarification of the molecular basis of the ABO gene, several studies have characterized the mechanism of ABO gene expression 2‐5 . The ABO antigens are expressed in a cell type–specific manner; the isoantigens A, B, and H of blood groups A, B, and O are not confined to red cells but are also found in most secretions and on some epithelial cells.…”