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2 results for “ABO allele haplotypes”
Data from: Haplotype sequence collection of ABO blood group alleles by long-read sequencing reveals putative A1-diagnostic variants
<p>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 <em>ABO</em> allele groups: <em>ABO</em>*<em>A1</em>/<em>A2</em>/<em>B</em>/<em>O.01.01</em>/<em>O.01.02</em>/<em>O.02</em>. We selected 77 samples from an <em>ABO</em> genotype dataset (n=25,200) of serologically-typed Swiss blood donors. The entire <em>ABO</em> 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 <em>ABO</em> group were re-sequenced using Illumina and PacBio technology. All 154 full-length <em>ABO</em> sequences were resolved as haplotypes. We observed novel, distinct sequence patterns for each <em>ABO</em> group. Most genetic diversity was found between, not within, <em>ABO</em> groups. Phylogenetic tree and haplotype network analyses highlighted distinct clades of each <em>ABO</em> group. Strikingly, our data uncovered four genetic variants putatively specific for <em>ABO</em>*<em>A1</em>, for which direct diagnostic targets are currently lacking. We validated <em>A1</em>-diagnostic potential using whole-genome data (n=4,872) of a multi-ethnic cohort. Overall, our sequencing strategy proved powerful for producing high-quality <em>ABO</em> 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 <em>ABO</em>, as well as studies about the function and evolutionary history of <em>ABO</em>.</p>
Data from: Haplotype sequence collection of ABO blood group alleles by long-read sequencing reveals putative A1-diagnostic variants
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