-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Identifying genetic variants of the ABO gene may reveal new biologic mechanisms underlying variant phenotypes of the ABO blood group. We report the molecular genetic analysis of 322 apparently unrelated ABO subgroup individuals in an estimated 2.1 million donors. STUDY DESIGN AND METHODS: We performed phenotype investigations by serology studies, analyzed the DNA sequence of the ABO gene by direct sequencing or sequencing after cloning, and evaluated promoter activity by reporter assays. RESULTS: In 62 rare ABO alleles, we identified 29 novel ABO subgroup alleles in 43 apparently unrelated subgroup individuals and their four available pedigrees. Of these alleles, one was a deletion-mutation allele, four were hybrid alleles, and 24 were point-mutation alleles. Most of the point mutations were detected in Exons 6 to 7, while several others were also detected in Exons 1 to 5 or splicing regions. One ABO promoter mutation, -35 to -18 del, was found and verified to reduce promoter activity, as determined by dual luciferase assays. Two mutations, 7G>T and 52C>T, carrying the premature terminal codons E3X and R18X in the 5'-region, were found to be associated with the very weak ABO subgroups "Ael" and "Bel." CONCLUSION: Twenty-nine ABO subgroup alleles were newly linked to different kinds of ABO variations. We provide the first evidence that promoter abnormality is involved in the formation of weak ABO phenotypes. We also described the first naturally occurring ABO alleles with premature terminal codons in the 5'-region that led to Ael and Bel phenotypes.
Transfusion 03/2013; · 3.22 Impact Factor
-
Blood transfusion = Trasfusione del sangue 06/2011; 9(4):466-8. · 2.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: B(x) is a very rare ABO blood group phenotype and the molecular mechanism underlying it still remains largely unknown. This study reports two novel B(x) alleles in two Chinese individuals.
Serologic investigations including serum transferase activity assay were performed with standard methods. DNA sequences of all seven exons and exon-intron boundaries of ABO gene were analyzed using genomic DNA by polymerase chain reaction and direct DNA sequencing or sequencing after gene cloning.
B(x) phenotypes were diagnosed in these two individuals. DNA analysis revealed that the ABO gene of the two B(x) individuals was heterozygous of O01/B alleles. Two novel heterozygous mutations 905A>G and 541T>C were identified, respectively, which resulted in the amino acid changes D302G and W181R in the B glycosyltransferases. The mutations were not found in 120 randomly selected samples.
Amino acid substitutions resulted from novel mutations 905A>G and 541T>C on ABO gene change highly conserved regions of the enzyme and may reduce the activity of the glycosyltransferases, leading to the B(x) phenotype.
Transfusion 09/2008; 48(11):2442-7. · 3.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This is a study on the allele composing of ABO, FUT1 and FUT2 gene loci of 10 para-Bombay individuals in China.
Ten samples coming from different districts of China were suspected of para-Bombay phenotype by primary serology tests. Routine and absorb-elution tests were conducted to identify their ABO type, and duplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to getting their ABO genotype. Most of them were submitted to a test of their Lewis type as well. Then through direct DNA sequencing with PCR products of FUT1 and FUT2 genes, the genotypes of their H and SE gene loci were analyzed.
It can be confirmed that the 10 samples are para-Bombay. All of their ABO genotypes are consistent with the serological absorb-elution results and the substances detected results in saliva. Seven out of 10 have recessive homozygous gene at their H locus. Each phenotype of h1h1 (nt547-552Deltaag), h2h2 (nt880-882Deltatt) and h4h4 (nt35 t-->c) are ascertained in 2 individuals; moreover, h3h3 (nt 658 c-->t) is identified in one individual. The rest are hh heterozygous individuals: one is h3/h(new-1); the other is h2/h(new-2); the last one is h1/h2. The h(new-1) (nt586 c-->t) allele has a point mutation at nt 586 C to T, which leads a nonsense mutation Gln(CAG) to stop (TAG).The second h (new-2) (nt328 g-->a) has an nt328 G to A missense mutation,which leads Ala (GCC),was replaced by Thr (ACC) at 110 amino acid position. All the 10 samples have Se (nt357 c-->t) synonymous mutation. One Bm(h) (B/O) individual with h4h4 phenotype has a Se(w)(nt357 c-->t; nt385 a-->t) allele, whose Lewis type is Le(a+b+). Moreover, the authors detected a (nt716 g-->a) mutation in two samples' Se gene.
Four kinds of known h alleles (h1-h4), 2 kinds of novel non-functional FUT1 alleles, a Se(w) allele, and a novel SeG716A polymorphism in Chinese para-Bombay individuals were detected. At the same time, the authors noticed that all the 10 samples have the nt357 c-->t mutation in their FUT2 gene.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 11/2004; 21(5):417-21.
-
[show abstract]
[hide abstract]
ABSTRACT: This is a study on some ABO subgroup samples which show discordant results of serological and molecular blood typing, the aim is to clarify their true ABO type by means of nucleotide analysis on exons 6 and 7 of their ABO gene.
Absorb-elution test and family investigation were conducted to study 7 samples which were involved in ABO grouping discrepancies. Duplex polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to identify their ABO genotypes. PCR products of exons 6 and 7 were cloned and sequenced.
All the 7 ABO subgroup samples with the discordant results of serological and molecular blood typing were found to have the normal O gene. Four out of them were typed as ABsub by serology, they were all of the A*102/O genotype. Sequencing analysis found all their A gene having the nt467 (C-->T) and nt803 (G-->C) mutation by comparison with the A*101 allele, i.e. their real type should be CisAB/O. Three out of 7 were typed as AsubB by serology and as BO by genotype; and point mutation was detected in all of their B gene. One of them had the nt700 (C-->G) mutation, the other 2 unrelated individuals had the novel nt640 (A-->G) mutation in their B alleles.
Through nucleotide analysis, 7 samples have been typed as AB subgroup in serology with the normal O gene, their real ABO type being CisAB in 4 cases and B(A) in 3 cases. At the same time, a kind of novel B (A)640 allele has been uncovered in this study.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 08/2004; 21(4):321-4.
