Multiplex structural variant detection by whole-genome mapping and nanopore sequencing

Sci Rep. 2022 Apr 20;12(1):6512. doi: 10.1038/s41598-022-10483-7.

Abstract

Identification of structural variants (SVs) breakpoints is important in studying mutations, mutagenic causes, and functional impacts. Next-generation sequencing and whole-genome optical mapping are extensively used in SV discovery and characterization. However, multiple platforms and computational approaches are needed for comprehensive analysis, making it resource-intensive and expensive. Here, we propose a strategy combining optical mapping and cas9-assisted targeted nanopore sequencing to analyze SVs. Optical mapping can economically and quickly detect SVs across a whole genome but does not provide sequence-level information or precisely resolve breakpoints. Furthermore, since only a subset of all SVs is known to affect biology, we attempted to type a subset of all SVs using targeted nanopore sequencing. Using our approach, we resolved the breakpoints of five deletions, five insertions, and an inversion, in a single experiment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosome Mapping
  • Genome
  • Genome, Human
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Nanopore Sequencing*
  • Sequence Analysis, DNA