Data from: Haplotype sequence collection of ABO blood group alleles by long-read sequencing reveals putative A1-diagnostic variants

In the era of blood group genomics, reference collections of complete and
fully-resolved blood group gene alleles have gained high importance. For
most blood groups, however, such collections are currently lacking, as
resolving full-length gene sequences as haplotypes (i.e. separated
maternal/paternal origin) remains exceedingly difficult with both Sanger
and short-read next-generation sequencing. Using the latest
third-generation long-read sequencing, we generated a collection of
fully-resolved sequences for all six main ABO allele groups:
ABO*A1/A2/B/O.01.01/O.01.02/O.02. We selected 77 samples from an ABO
genotype dataset (n=25,200) of serologically-typed Swiss blood donors. The
entire ABO gene was amplified in two overlapping long-range PCRs (covering
~23.6 kb) and sequenced by long-read Oxford Nanopore sequencing. For
quality validation, two samples per ABO group were re-sequenced using
Illumina and PacBio technology. All 154 full-length ABO sequences were
resolved as haplotypes. We observed novel, distinct sequence patterns for
each ABO group. Most genetic diversity was found between, not within, ABO
groups. Phylogenetic tree and haplotype network analyses highlighted
distinct clades of each ABO group. Strikingly, our data uncovered four
genetic variants putatively specific for ABO*A1, for which direct
diagnostic targets are currently lacking. We validated A1-diagnostic
potential using whole-genome data (n=4,872) of a multi-ethnic cohort.
Overall, our sequencing strategy proved powerful for producing
high-quality ABO haplotypes and holds promise for generating similar
collections for other blood groups. The publicly available collection of
154 haplotypes will serve as a valuable resource for molecular analyses of
ABO, as well as studies about the function and evolutionary history of
ABO.