Long read nanopore sequencing for detection of HLA and CYP2D6 variants and haplotypes

The main purpose of this study was to demonstrate the utility of Oxford Nanopore’s MinION sequencing technology in resolving variants and haplotypes of pharmacogenes, specifically CYP2D6 and HLA genes. These genes are clinically relevant for determining patient drug responses, as they influence drug metabolism and immunological reactions. Traditional sequencing methods often fail to resolve haplotypes accurately, which can lead to incomplete or erroneous genotyping. This study aimed to overcome those limitations by using long-read sequencing to provide accurate haplotype resolution.

Oxford Nanopore’s MinION sequencer was used for the long-read sequencing of CYP2D6, HLA-A, and HLA-B genes. This technology allowed the authors to reconstruct the haplotypes without the need for statistical phasing, demonstrating its potential for clinical applications in pharmacogenomics.

The major findings of the study showed that the MinION sequencing device was able to produce sufficiently long reads to resolve haplotypes and detect clinically relevant variants in CYP2D6, including loss-of-function alleles such as CYP2D6*3 and CYP2D6*4. Additionally, the study highlighted the potential of this technology to detect complex variants in HLA genes, which are highly polymorphic. The study demonstrated that with sufficient sequencing coverage, nanopore sequencing could provide accurate consensus sequences and resolve medically actionable haplotypes, offering promise for its use in clinical pharmacogenomics.