ABO exon and intron analysis in individuals with the AweakB phenotype reveals a novel O1v-A2 hybrid allele that causes four missense mutations in the A transferaseReportar como inadecuado

ABO exon and intron analysis in individuals with the AweakB phenotype reveals a novel O1v-A2 hybrid allele that causes four missense mutations in the A transferase - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Genetics

, 4:17

First Online: 17 November 2003Received: 05 September 2003Accepted: 17 November 2003


BackgroundSince the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood-group ABO locus, polymorphisms due to ethnic and-or phenotypic variations have been reported. Some subgroups have been explained at the molecular level, but unresolved samples are frequently encountered in the reference laboratory.

ResultsABO blood grouping discrepancies were investigated serologically and by ABO genotyping duplex polymerase-chain-reaction PCR – restriction-fragment-length-polymorphism RFLP and PCR – allele-specific-primer ASP across intron 6 and DNA sequencing of the ABO gene and its proposed regulatory elements. Blood samples from five individuals living in Portugal, Switzerland, Sweden and the USA were analysed. These individuals were confirmed to be of Black ethnic origin and had the unusual AweakB phenotype but appeared to have the AB genotype without previously reported mutations associated with weak A or B expression. Sequencing of this A allele having 467C>T and 1061delC associated with the common A A201 allele revealed three mutations regularly encountered in the OO02 allele: 106C>T Val36Phe, 188G>A Arg63His, 220C>T Pro74Ser in exons 3, 4 and 5, respectively. The additional presence of 46G>A Ala16Thr was noted, whilst 189C>T that normally accompanies 188G>A in Owas missing, as were all O-related mutations in exons 6 and 7 261delG, 297A>G, 646T>A, 681G>A, 771C>T and 829G>A. On screening other samples, 46G>A was absent, but two new O alleles were found, a Jordanian O and an African Oallele having 188G>A but lacking 189C>T. Sequencing of introns 2, 3, 4 and 5 in common alleles A A101, A, B B101, O, Oand O O03 revealed 7, 12, 17 and 8 polymorphic positions, respectively, suggesting that alleles could be defined by intronic sequences. These polymorphic sites allowed definition of a breakpoint in intron 5 where the O-related sequence was fused with A to form the new hybrid. Intron 6 has previously been sequenced. Four new mutations were detected in the hybrid allele and these were subsequently also found in intron 6 of A alleles in other Black African samples.

ConclusionsA novel O-A hybrid was defined by ABO exon-intron analysis in five unrelated individuals of African descent with the AweakB blood group phenotype.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2156-4-17 contains supplementary material, which is available to authorized users.

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Autor: Bahram Hosseini-Maaf - Åsa Hellberg - Maria J Rodrigues - M Alan Chester - Martin L Olsson

Fuente: https://link.springer.com/article/10.1186/1471-2156-4-17

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