Abstract

Variants larger than a single base-pair substitution comprise 34% of all disease-causing variation. Furthermore, large structural variants are over 30 times as likely to affect gene expression compared to single nucleotide variants1, and are associated with an increasing number of phenotypic variations in health and common and rare diseases2. Nanopore-based sequencing technology from Oxford Nanopore Technologies ― developed for real-time, high-performance, accessible, and scalable analysis of DNA and RNA ― provides the capability of gaining a more comprehensive picture of human genomic variation than ever before. Long and ultra-long sequence reads span large structural variants and repetitive regions, enabling accurate calling and phasing of variants and epigenetic modifications, as well as isoform-level expression analyses. This presentation will highlight key examples where nanopore sequencing technology has generated new insights into rare disease and cancer research, through a comprehensive, multi-omics view of genetic variation. 1. Eichler, E. E. N Engl J Med. 381(1):64-74 2. Weischenfeldt, J. et al. Nat Rev Genet. 14:125-138 (2013).