Speaker details:

Heather Stark, Strategic Account Manager - , Oxford Nanopore Technologies

Heather Stark Strategic Account Manager Biography Heather is one of the newest members of the Oxford Nanopore team, having just joined in April 2020. She has a combined 25 years of experience working in R&D assay development in both biotech industry and academic environments, as well as account management for various sequencing manufacturers. Heather graduated from The University of Nebraska, where she majored in biochemi stry with an emphasis in molecular biology.

Christopher M. Watson, Saint James’s University Hospital, Leeds

Dr. Watson studied molecular bio logy and human genetics at the University of Manchester and Mayo Clinic, Florida. He subsequently moved to Leeds to undertake clinical scientist training, attaining HCPC registration in 2013. As the NHS lead in the Translational Genomics Unit, he has overseen the clinical implementation of numerous short - read sequencing instruments and next - generation sequencing assays. He is currently a visiting research fellow at the University of Leeds, where he is focused on understanding the clinical utility of long - read sequencing, particularly for the diagnosis of rare Mendelian disease.

Title and abstract

Characterising structural variants and mobile element insertions using long - read nanopore sequencing

The widespread implementation of low - cost genome - wide diagnostic screening tests is resulting in identification of an increasing number of possibly pathogenic dosage or complex variants affecting single genes. Clinical management demands facile validation of such findings, requiring the design of custom variant - specific assays. We describe our experience using a Cas9 enrichment strategy, combined with long - read MinION sequencing to define structural variants at nucleotide resolution. We further detail our implementation of Flongle - based sequencing for the characterisation of complex mobile element insertions, which are typically refractory to analysis by short - read sequencing workflows.

Belén de la Morena-Barrio, University of Murcia

Belén de la Morena - Barrio graduated in Pharmacy in 2015 and is currently completing a Ph.D. in the group of Prof. Javier Corral at the University of Murcia, Spain. Her research is focused on the identification of new molecular mechanisms involved in antithrombin deficiency by evaluating cases with unknown molecular diagnosis , and characterising structural variants involved in this disorder. She is an expert in third - generation sequencing thanks to her training in the group of Prof. Willem Ouwehand at the University of Cambridge. In three years of her Ph.D., she has published eight articles , and is the first author in three of them.

Title and abstract

Genetic dissection of structural variants affecting SERPINC1 by long - read whole genome sequencing in the largest cohort of patients with antithrombin deficiency: characterisation of the first complex structural variant

The identification and characterisation of structural variants (SVs) is challenging. In antithrombin deficiency (ATD) , MLPA detects SVs in > 8% of cases, but doesn't inform about the extension and breakpoint sequence. We performed Long Range - PCR (LR - PCR), NGS, CGH array and/or nanopore sequencing (Oxford Nanopore) in eighteen patients wit h SVs detected by MLPA. Oxford Nanopore technology detected all SVs independently of its size or type, resolving the breakpoint sequence, and identified the first complex SV which was miss-classified by MLPA and LR - PCR. This study revealed repetitive element s involved in all the SVs. Our study underscores the utility of Oxford Nanopore technology to fully characterise SVs causing ATD.