Nanopore sequencing reveals a structural alteration of mirror-image duplicated genes in a genome-editing mouse line

Congenit Anom (Kyoto). 2020 Jul;60(4):120-125. doi: 10.1111/cga.12364. Epub 2019 Dec 25.

Abstract

CRISPR-Cas9 technology has been used in various studies; however, it has also been found to introduce unexpected structural alternations. In this study, we used nanopore sequencing to characterize an unexpected structural alteration of mirror-image duplicated genes in a mouse line, in which we aimed to delete a part of the duplicated genes using genome editing. We removed low-molecular-weight DNA fragments and increased the input, which led to improved sequence performance. With 14.9 Gb input for whole-genome analysis, we detected a complex structural alteration involving inversion and deletion, which appears to be difficult to characterize with short-read sequencers. Therefore, our study clearly showed the utility of nanopore sequencing for characterizing unexpected complex structural alterations caused by genome editing.

Keywords: Gml; Gml2; duplicated gene; long-read sequencer.

MeSH terms

  • Animals
  • CRISPR-Cas Systems / genetics*
  • DNA / genetics
  • Gene Duplication / genetics*
  • Gene Editing*
  • Humans
  • Mice
  • Nanopore Sequencing*

Substances

  • DNA