Cas9-based enrichment and single-molecule sequencing for precise characterization of genomic duplications.

ABSTRACT: The widespread use of genome-wide diagnostic screening methods has greatly increased the frequency with which incidental (but possibly pathogenic) copy number changes affecting single genes are detected. These findings require validation to allow appropriate clinical management. Deletion variants can usually be readily validated using a range of short-read next-generation sequencing (NGS) strategies, but the characterization of duplication variants at nucleotide resolution remains challenging. This presents diagnostic problems, since pathogenicity cannot generally be assessed without knowing the structure of the variant. We have used a novel Cas9 enrichment strategy, in combination with long-read single-molecule nanopore sequencing, to address this need. We describe the nucleotide-level re

SUBMITTER: Watson CM 

PROVIDER: S-EPMC6923135 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature