Genetic and mechanistic evaluation for the weak <scp>A</scp> phenotype in <scp>A</scp><sub>el</sub> blood type with <scp>IVS</scp>6 + 5<scp>G</scp>&gt;<scp>A ABO</scp> gene mutation

Chen, D.‐P.; Sun, Chien‐Feng; Ning, Hsiao-Chen; Peng, Chien-Ting; Wang, W.‐T.; Tseng, Ching Ping

doi:10.1111/vox.12196

Cited by 13 publications

(6 citation statements)

References 26 publications

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“…Clinically, subtype A is divided into A1, A2, A3, Ax, Aend, Am and Ael according to decreasing number of A antigens [10], among which Ael subtype contains the least number of A antigen on the red blood cells. The reactivity of Ael red blood cells can be detected only by absorption‐elution experiments, and its serum does not agglutinate or weakly agglutinate with type A red blood cells, that is, A elution type [11–13].…”

Section: Discussionmentioning

confidence: 99%

Detection and phenotype analysis of a novel Ael blood group allele

Wang,

Tang,

Zhang

et al. 2023

Vox Sanguinis

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Background and ObjectivesThe presence of blood subtypes may lead to difficulties in blood group identification; however, third‐generation sequencing (TGS) can help in accurately identifying difficult blood groups, and study the serological characteristics and molecular mechanism of Ael subtypes.Materials and MethodsABO blood group was identified by the standard serological technique, weak blood group antigen was identified by adsorption‐elution experiments, ABH substance in the saliva was determined and glycosyltransferase activity of A and B was detected. The ABO gene full‐length sequence and promoter region were amplified by specific primers using single‐molecule real‐time sequencing, with the amplified products being sequenced directly and analysed in real time.ResultsThe patient was serologically identified as Ael subtype, and TGS analysis revealed new intron mutations in Ael patients (c.467C>T; c.29‐10T>A).ConclusionThe discovery of the new allele and the identification of ABO subtypes can be combined with serological characterization and molecular biological methods.

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Section: Discussionmentioning

confidence: 99%

Detection and phenotype analysis of a novel Ael blood group allele

Wang,

Tang,

Zhang

et al. 2023

Vox Sanguinis

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“…Some variations in the splice sites of the ABO gene are associated with some ABO subtypes. Chen DP et al reported c.155 + 5G > A (IVS3 + 5G > A) in a B3 individual and c.374 + 5G > A (IVS6 + 5G > A) in an Ael individual 31 , 32 . In theory, changes in the ABO gene splice site result in the formation of new RNA splice sites and therefore novel versions of ABO mRNA.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple ABO mRNA forms were detected in the normal ABO phenotype by RT–PCR, the majority of which lacked exon 6 [ 34 , 35 ]. However, in some individuals with ABO subtypes, RNA splicing of the ABO gene was detected [ 31 , 32 , 36 , 37 ]. An ABO* A1-like allele with a 4 bp deletion (c.236-239delCGTG) in exon 5 and a 20 bp downstream deletion in intron 5 affected the donor splice site [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…While it is possible to generate a mRNA without the matching exon 3 fragment, only one of 102 mRNA clones contained an exon 3 deletion splicing variant, suggesting that further variable splicing occurred [ 31 ]. The c.374 + 5G > A variant originally identified on the ABO*A1.01 allele in the Ael individual, currently referred to as the ABO*AEL.04 allele , is predicted to generate transcripts without exon 6 or exons 5 to 6 32 . At least 10 distinct splicing transcript types were identified in the ABO*AEL.04 individual [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Six splice site variations, three of them novel, in the ABO gene occurring in nine individuals with ABO subtypes

et al. 2021

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Background Nucleotide mutations in the ABO gene may reduce the activity of glycosyltransferase, resulting in lower levels of A or B antigen expression in red blood cells. Six known splice sites have been identified according to the database of red cell immunogenetics and the blood group terminology of the International Society of Blood Transfusion. Here, we describe six distinct splice site variants in individuals with ABO subtypes. Methods The ABO phenotype was examined using a conventional serological method. A polymerase chain reaction sequence-based typing method was used to examine the whole coding sequence of the ABO gene. The ABO gene haplotypes were studied using allele-specific primer amplification or cloning technology. In silico analytic tools were used to assess the functional effect of splice site variations. Results Six distinct variants in the ABO gene splice sites were identified in nine individuals with ABO subtypes, including c.28 + 1_2delGT, c.28 + 5G > A, c.28 + 5G > C, c.155 + 5G > A, c.204-1G > A and c.374 + 5G > A. c.28 + 1_2delGT was detected in an Aw individual, while c.28 + 5G > A, c.28 + 5G > C, and c.204-1G > A were detected in Bel individuals. c.155 + 5G > A was detected in one B3 and two AB3 individuals, whereas c.374 + 5G > A was identified in two Ael individuals. Three novel splice site variants (c.28 + 1_2delGT, c.28 + 5G > A and c.28 + 5G > C) in the ABO gene were discovered, all of which resulted in low antigen expression. In silico analysis revealed that all variants had the potential to alter splice transcripts. Conclusions Three novel splice site variations in the ABO gene were identified in Chinese individuals, resulting in decreased A or B antigen expression and the formation of ABO subtypes.

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“…Многообразие аллельных вариантов антигена А обусловлено либо миссенсмутациями в гене АВО*А (точечными заменами нуклеотидов в кодирующей ча сти гена АВО*А, ведущими к замене аминокислоты в соответствующем белковом продукте) либо сплай синговыми мутациями (затрагивающими сайты сплай синга или создающими новые сайты сплайсинга в инт ронных областях гена, что сопровождается либо делецией смежного с мутацией экзона, либо наруше нием удаления соответствующего интрона при про цессинге первичного РНКтранскрипта). Многие сплайсинговые мутации приводят к сдвигу рамки счи тывания или к формированию стопкодона, что при водит к синтезу функционально неактивной Аглико зилтрансферазы [3].…”

Section: Discussionunclassified

Molecular serological characteristics of ABO system A antigen

et al. 2021

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Background. One of the polymorphic antigens in the ABO system is antigen A, which includes many allelic variants with different expression. Immunological methods for determining the blood group of the ABO system have limitations in their use, including due to the presence of weekly expressed antigens in humans. For the correct determination of blood group according to the ABO system, genetic typing is becoming increasingly important. 89 alleles of the ABO*A gene are known. Knowledge of ABO*A gene polymorphisms and their prevalence contributes to the prevention of errors in determining the blood group of donors and recipients.Objective: to describe variants of ABO*A gene alleles in Russians and serological characteristics of the antigens encoded by them.Materials and methods. The blood of 14,000 people was examined. The blood group was determined using anti-A, anti- Aweak, anti-B, lectin (anti-A1) and gel cards. A molecular study of ABO*A gene polymorphisms was conducted in 151 people. Polymerase chain reaction with sequence-specific primers and direct Sanger sequencing were used.Results. 7 different ABO*A alleles were detected, including the ABO*A1.01 and ABO*A1.02 alleles. In 118 individuals with a weak A antigen, the ABO*A2.01 allele was the most frequent (87.29 %). Rare alleles ABO*A2.06 (5.93 %), ABO*AW.06 (4.23 %), ABO*A2.09 (0.85 %) and ABO*Ax (1.70 %) were found. Serological characteristics of A antigens variants depending on genotypes are described, variants A1, A2, A3 and very weak A were detected. Extraagglutinins α1 were absent in all persons with weakened A antigen.Conclusion. Small or mixed agglutination with Coliclones or red blood cell stratification in the gel suggest the presence of antigen A with weakened expression. Modern molecular methods make it possible to identify rare gene alleles and genotypes. Erythrocyte genomics helps to resolve the ambiguity of the serological results allows understanding the true mechanisms of particular phenotype formation and makes a contribution to ensuring the immunological safety of blood components transfusions.

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Genetic and mechanistic evaluation for the weak A phenotype in A_el blood type with IVS6 + 5G>A ABO gene mutation

Abstract: This study demonstrates that aberrant splicing of A transcripts contributes to weak A expression and the weak agglutination of Ael -RBCs, adding to the complexity for the regulatory mechanisms of ABO gene expression.

Cited by 13 publications

References 26 publications

Detection and phenotype analysis of a novel Ael blood group allele

Detection and phenotype analysis of a novel Ael blood group allele

Six splice site variations, three of them novel, in the ABO gene occurring in nine individuals with ABO subtypes

Molecular serological characteristics of ABO system A antigen

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Genetic and mechanistic evaluation for the weak A phenotype in Ael blood type with IVS6 + 5G>A ABO gene mutation

Abstract: This study demonstrates that aberrant splicing of A transcripts contributes to weak A expression and the weak agglutination of Ael -RBCs, adding to the complexity for the regulatory mechanisms of ABO gene expression.

Cited by 13 publications

References 26 publications

Detection and phenotype analysis of a novel Ael blood group allele

Detection and phenotype analysis of a novel Ael blood group allele

Six splice site variations, three of them novel, in the ABO gene occurring in nine individuals with ABO subtypes

Molecular serological characteristics of ABO system A antigen

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Genetic and mechanistic evaluation for the weak A phenotype in A_el blood type with IVS6 + 5G>A ABO gene mutation