Genetic characterization of an ABO*O.01.02-A2.05 hybrid allele associated with the Ael phenotype in a Chinese individual

Abstract

Background

Discrepancies in ABO typing can arise from genetic variations, posing risks in transfusions. Traditional sequencing handles point mutations well but struggles with recombination events, which long-read sequencing can accurately identify. Here, we report a case of A_el phenotype associated with a novel recombination allele in the ABO gene in a Chinese individual.

Study design and methods

We used serological methods to identify the phenotype, and applied sequencing-based typing (SBT) and third-generation long-read sequencing (TGS) to determine the ABO genotype.

Results

Serological testing revealed an A_el subtype. SBT sequencing identified seven heterozygous mutation sites, with one allele hypothesized as ABO*O.01.01 (c.261delG). The remaining six variants did not match any known allele combination. Two ABO haplotype sequences were obtained through TGS. Analysis confirmed a second haplotype as a hybrid of O.01.02-A02.05, with the breakpoint located between c.220C>T (g.chr9: 133258116C>T; p.Pro74Ser) and c.239+103delCCC (g.chr9: 133257993delCCC) . The novel allele sequence has been submitted to GenBank (Accession number: OR2834978).

Conclusion

Our study demonstrates a case of a Chinese individual with an A_el phenotype caused by a novel allele resulting from the recombination of O.01.02 and A2.05. This finding underscores the significant advantage of long-read TGS technology in resolving structural variations.