Oxford Nanopore sequencing technology used to characterise inheritance of specific familial variants in under three hours from birth

In a preprint released today, a team from University of Washington and Seattle Children’s Hospital describe an ultra-rapid analysis using whole genome sequencing with Oxford Nanopore technology and prior information about a genetic disease to target a single gene

Ultra-rapid sequencing

Oxford Nanopore sequencing technology has been used as part of a workflow designed to assess heritance of specific familial variants as quickly as possible after birth. In a preprint publication released today on MedRxiv a team led by Danny Miller, Assistant Professor at University of Washington and Seattle Children’s Hospital, demonstrate how prior genetic information could be leveraged with nanopore sequencing to speed the analysis. The authors highlight that prior information about a variant of concern is often available including a specific gene and specific variants that can identify the affected haplotypes. In the case described, a newborn’s older sibling was affected by a single gene disorder and using this rapid analysis it was confirmed that the child was not affected (and was not a carrier) for the specific genetic condition and the answer was achieved in less than 3 hours from birth.

The team were also able to demonstrate that many known variants could be accurately detected at three hours. The team utilised a modified version of Oxford Nanopore’s rapid library preparation to make this process faster than ligation methods and to reduce the amount of blood required, which is vital in newborns due to restrictions on daily blood draws.

The study used Oxford Nanopore’s high-throughput sequencing device, the PromethION 24 which is capable of running up to 24 flow cells at once and is therefore uniquely designed to enable accelerated sequencing and to deliver ultra-rapid analysis. In this case they used 20 PromethION Flow Cells in parallel for whole genome sequencing followed by single-gene analysis.

This study is proof of concept that with prior knowledge of familial variants and accelerated nanopore sequencing it is possible to evaluate an individual at risk for a genetic disease rapidly after birth. The paper can be accessed in full here.