Nanopore sequencing resolves challenging medically relevant genes (CMRG), focusing on SMN

Abstract:

Currently there are 395 identified challenging medically relevant genes (CMRGs)1. These are genes with regions that are difficult to resolve using traditional sequencing methods. Here we address two categories of CMRG's: repeat expansions (i.e. FMR1, HTT and RFC1) and highly homologous genes (i.e. SMN1/2, CYP21A2/1P).

SMN1 and SMN2 copy numbers were correctly identified in a set of 20 samples with a range of SMN1 and SMN2 copies, with detection of the structural variant exon 7-8 deletion. Additionally, repeat expansions were correctly enumerated in HTT, FMR1 and RFC1 with the motif sequence identified in the repeat region of RFC1. This shows nanopore long read sequencing enabling haplotype analysis of repeat expansions and highly homologous genes.