ArticleClinical chemistry2025
Allelic Cataloging of RHD-RHCE Reference Sequences Using Targeted Long-Read Sequencing.
Article in Clinical chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Towards haplotypes of blood group genes: the impact of long-read sequencing in molecular immunohematology.Annals of translational medicine · 2026Article
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7 authors.
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Abstract
backgroundImplementation of blood group genotyping has offered substantial benefits in transfusion medicine. However, the complex molecular basis of Rh antigen expression and a high degree of sequence homology between RHD and RHCE have long limited the accuracy of blood group genotyping, highlighting the need for a more systematic characterization of existing molecular variations.
methodsWe employed a custom target enrichment strategy to perform high-fidelity (HiFi) long-read sequencing of the RHD-RHCE region on chromosome 1 in samples obtained from 63 individuals. The resulting HiFi long-read sequences were aligned to the human reference genome GRCh38, variants were identified and phased, and allelic reference sequences were generated. Phylogenetic analyses were then performed to classify RHD-RHCE alleles and elucidate their evolutionary relationships.
resultsOur approach enabled the phasing of heterozygous variants at distant loci, as well as precise characterization of tandem repeat variations and structural variants. Complete phase resolution was achieved in 76.2% of samples, yielding 96 allelic reference sequences spanning the entire RHD-RHCE region. Alleles within each phylogenetic clade exhibited a characteristic sequence pattern spanning RHD to RHCE.
conclusionsOur findings revealed that the current Eurasian allelic pool originated from 2 distinct primordial lineages, with occasional interallelic recombination events shaping the present-day RHD-RHCE haplotype diversity. While most previous classification approaches have treated RHD and RHCE independently, our results support the notion that analyzing them as a single evolutionary unit may offer practical advantages for molecular typing approaches.
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