ABO genotyping with next‐generation sequencing to resolve heterogeneity in donors with serology discrepancies

Wu, Ping; Lin, Yin-Hung; Tsai, Lei Fang; Chen, Ming Hung; Chen, Pei‐Lung; Pai, Shun-Chung

doi:10.1111/trf.14654

Cited by 38 publications

(47 citation statements)

References 46 publications

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“…) . ABO was also excluded from this analysis, as accurate prediction of this phenotype often requires precise phasing algorithms …”

Section: Resultsmentioning

confidence: 99%

“…3,5 Transfusion medicine is an additional discipline with a strong genetics foundation that is exploring this approach. [6][7][8][9][10][11][12][13][14][15][16][17] The genetic basis of blood groups has been largely elucidated and applied by commercially available red blood cell (RBC) genotyping platforms. The International Society for Blood Transfusion (ISBT) recognizes 36 blood group systems, encompassing 41 genes and over 1100 haplotype alleles.…”

Section: Resultsmentioning

confidence: 99%

“…Distinguishing neutral passenger variants from deleterious mutations has challenged genomics from its inception, and as NGS is applied to transfusion medicine, novel blood group variants have been a recurrent finding . Several prediction tools used widely in genomics have not been tested for immunohematology.…”

Section: Discussionmentioning

confidence: 99%

“…A number of successful clinical applications have been reported, and further efforts are under way in the areas of oncology, hemostasis, obstetrics, and pharmacology to identify the clinical benefits of genomic medicine . Transfusion medicine is an additional discipline with a strong genetics foundation that is exploring this approach …”

mentioning

confidence: 99%

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Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

et al. 2018

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BACKGROUND The 1000 Genomes Project provides a database of genomic variants from whole genome sequencing of 2504 individuals across five continental superpopulations. This database can enrich our background knowledge of worldwide blood group variant geographic distribution and identify novel variants of potential clinical significance. STUDY DESIGN AND METHODS The 1000 Genomes database was analyzed to 1) expand knowledge about continental distributions of known blood group variants, 2) identify novel variants with antigenic potential and their geographic association, and 3) establish a baseline scaffold of chromosomal coordinates to translate next‐generation sequencing output files into a predicted red blood cell (RBC) phenotype. RESULTS Forty‐two genes were investigated. A total of 604 known variants were mapped to the GRCh37 assembly; 120 of these were reported by 1000 Genomes in at least one superpopulation. All queried variants, including the ACKR1 promoter silencing mutation, are located within exon pull‐down boundaries. The analysis yielded 41 novel population distributions for 34 known variants, as well as 12 novel blood group variants that warrant further validation and study. Four prediction algorithms collectively flagged 79 of 109 (72%) known antigenic or enzymatically detrimental blood group variants, while 4 of 12 variants that do not result in an altered RBC phenotype were flagged as deleterious. CONCLUSION Next‐generation sequencing has known potential for high‐throughput and extended RBC phenotype prediction; a database of GRCh37 and GRCh38 chromosomal coordinates for 120 worldwide blood group variants is provided as a basis for this clinical application.

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“…) . ABO was also excluded from this analysis, as accurate prediction of this phenotype often requires precise phasing algorithms …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

et al. 2018

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“…The studies above demonstrate the capability for targeted sequencing for donors who contribute red cells for antibody typing panels (Fichou & Ferec, ; Jakobsen et al , ; Schoeman et al , ) resolving complex serology problems to inform donor or transfusion management (Schoeman et al , ; Wu et al , ) signalling the presence of antigens with weakened expression typed as negative by serology and not included on SNV panels (Schoeman et al , ; Wu et al , ) detecting novel or rare population variants in association with altered phenotypes and defining variants associated with high or low frequency antigens for which serology reagents are rare or not available …”

Section: Targeted Exome Sequencing In Red Cell Reference Laboratory Smentioning

confidence: 99%

Developments beyond blood group serology in the genomics era

2019

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Summary Blood group serology and single nucleotide polymorphism‐based genotyping platforms are accurate but do not provide a comprehensive cover for all 36 blood group systems and do not cover the antigen diversity observed among population groups. This review examines the extent to which genomics is shaping blood group serology. Resources for genomics include the Human Reference Genome Sequence assembly; curated blood group tables listing variants; public databases providing information on genetic variants from world‐wide studies; and massively parallel sequencing technologies. Blood group genomic studies span the spectrum, from bioinformatic data mining of huge data sets containing whole genome and whole exome information to laboratory investigations utilising targeted sequencing approaches. Blood group predictions based on genome sequencing and genomic studies are proving accurate, and have shown utility in both research and reference settings. Overall, studies confirm the potential for blood group genomics to reshape donor and patient transfusion management strategies to provide more compatible blood transfusions.

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Allele‐specific long‐range sequencing as a method for ABO haplotyping in clinical blood group diagnosis and immunohematology research

Matzhold,

Drexler‐Helmberg,

Helmberg

et al. 2023

Molec Gen & Gen Med

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BackgroundSafe transfusion therapy requires accurate testing of blood donors and recipients to determine their ABO blood group compatibility. Genotyping does not always clarify serological blood typing discrepancies and conventional PCR methods are not suitable to identify ABO haplotypes. Therefore, an allele‐specific long‐range sequencing‐based typing method was established.MethodsStudy samples (n = 100) and six patient samples were ABO phenotyped and screened for specific single nucleotide polymorphisms (SNP) in the ABO gene. Based on identified heterozygous SNPs in intron 1 (12897G>A), 2 (437C>T) or 4 (102C>A, 1511G>T) both ABO alleles were investigated separately using a high‐fidelity long‐range PCR system and Sanger sequencing. The alleles were correlated to the ABO phenotypes determined.ResultsDirect sequencing of allelic PCR products up to 6743 bases has been successful in discriminating common combinations of the ABO*A1.01, ABO*A2.01, ABO*B.01, ABO*O.01.01, ABO*O.01.02 and ABO*O.02.01 alleles. 10 out of 64 haplotypes were found to be not previously described. The uncommon ABO*AW.31.01 and the unusual O alleles ABO*O.05 and ABO*O.02.03 alleles were detected in patient samples, resolving the initial inconclusive serologic ABO typing results.ConclusionThis method is an effective tool for analyzing ABO haplotypes. Applicable for ABO molecular diagnostics and immunohematology research it may help to improve pre‐transfusion blood type testing.

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ABO genotyping with next‐generation sequencing to resolve heterogeneity in donors with serology discrepancies

Abstract: This study demonstrated a full coverage of ABO by capture-based panel, phasing analysis with NGS in ABO genotyping resolved heterogeneity with novel allele and microchimerism findings. This approach provided a more precise method for subtyping and thereby leading to safer transfusion.

Cited by 38 publications

References 46 publications

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

Genomic coordinates and continental distribution of 120 blood group variants reported by the 1000 Genomes Project

Developments beyond blood group serology in the genomics era

Allele‐specific long‐range sequencing as a method for ABO haplotyping in clinical blood group diagnosis and immunohematology research

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