Scalable detection of technically challenging variants through modified next-generation sequencing.

ABSTRACT:

Background

Some clinically important genetic variants are not easily evaluated with next-generation sequencing (NGS) methods due to technical challenges arising from high- similarity copies (e.g., PMS2, SMN1/SMN2, GBA1, HBA1/HBA2, CYP21A2), repetitive short sequences (e.g., ARX polyalanine repeats, FMR1 AGG interruptions in CGG repeats, CFTR poly-T/TG repeats), and other complexities (e.g., MSH2 Boland inversions).

Methods

We customized our NGS processes to detect the technically challenging variants mentioned above with adaptations including target enrichment and bioinformatic masking of similar sequences. Adaptations were validated with samples of known genotypes.

Results

Our adaptations provided high-sensitivity and high-specificity detection for most of the varian

SUBMITTER: Rojahn S 

PROVIDER: S-EPMC9747563 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature