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Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell‐specific enhancer‐like element and the ABO promoter in individuals with phenotypes A 3 and B 3 , respectively
Author(s) -
Takahashi Y.,
Isa K.,
Sano R.,
Nakajima T.,
Kubo R.,
Takahashi K.,
Kominato Y.,
Michino J.,
Masuno A.,
Tsuneyama H.,
Ito S.,
Ogasawara K.,
Uchikawa M.
Publication year - 2014
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/vox.12136
Subject(s) - enhancer , biology , abo blood group system , point mutation , microbiology and biotechnology , allele , genetics , promoter , gene , phenotype , regulatory sequence , mutation , nucleotide , single nucleotide polymorphism , transcription factor , gene expression , genotype
Background and objectives An erythroid cell‐specific regulatory element, referred to as the +5.8‐kb site, has been identified in the first intron of the human ABO blood group gene. Subsequent studies have revealed involvement of deletion or mutation at the site in phenotypes A m , B m and AB m . We investigated the molecular mechanisms involved in the A 3 and B 3 phenotypes. Materials and methods Genomic DNA s were prepared from peripheral blood of seven A 3 individuals and twelve B 3 or AB 3 individuals, and the nucleotide sequences were investigated using PCR and sequencing. Promoter assays were performed with K562 cells. Results Two single point‐mutations at +5893 or +5909 in the site on the A ‐allele were found in A 3 individuals, while promoter assays revealed decreased activity at the site as a result of each substitution. In two B 3 individuals, a single point‐mutation at −77 in the ABO promoter on the B ‐allele was found, and the substitution was demonstrated to reduce the promoter activity. Conclusion Nucleotide substitutions in the transcriptional regulatory elements such as the +5.8‐kb site and the ABO promoter appear to decrease transcription from the A‐ and B ‐alleles, resulting in reduction in A‐ and B‐antigen expression in A 3 and B 3 , respectively.