ArticleBlood advances2026
Proof-of-principle: nanopore adaptive sampling enables full blood group genome analysis and resolution of hybrid alleles.
Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Unraveling missing variants through target capture-based long-read sequencing in autosomal recessive disorders.European journal of human genetics : EJHG · 2026Article
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10 authors.
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Abstract
abstractAdaptive sampling (AS), a computational enrichment method developed for Oxford Nanopore Technologies sequencing platforms, offers a promising advance in molecular blood group diagnostics. By leveraging long-read sequencing, AS has the potential to accurately resolve complex structural variants in the RH and MNS blood group systems, while characterizing the entire blood group genome through a simple, fast and locus-adjustable protocol. As proof-of-principal, we evaluated the performance of AS using 5 samples with suspected complex variants in the RH and MNS systems, unresolved by standard immunohematological methods. Samples were sequenced on a PromethION P2 Solo with up to 2 samples per flowcell, generating 37.0 to 52.4 gigabases of data with mean on-target coverages of 18.9× to 53.4×, allowing reliable variant detection. Hybrid alleles were characterized using a de novo assembly approach, whereas variants in nonrecombinant regions were analyzed using both a custom in-house and the EPI2ME reference-based workflow. With reference to field-specific allele collections, 10% to 15% of detected alleles contained novel nonsynonymous single-nucleotide variants (SNVs) or unreported exonic SNV combinations. All suspected hybrid alleles were successfully assembled and identified as GYP∗401.02, RHD∗03N.01, and RHD∗01EL.44, representing, to our knowledge, the first fully characterized haplotypes for these variants publicly available. Overall, AS showed significant potential for advancing blood group genomics by enabling high-resolution, full-gene analysis. Its ability to support high-throughput donor genotyping and precise patient-donor matching may reduce the risk of alloimmunization and delayed hemolytic transfusion reactions, particularly in patients who receive chronic transfusions. These findings highlight AS as a powerful tool for both research and clinical applications in transfusion medicine.
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