A Novel Approach for the Identification of Pharmacogenetic Variants in MT-RNR1 through Next-Generation Sequencing Off-Target Data.

ABSTRACT: Specific genetic variants in the mitochondrially encoded 12S ribosomal RNA gene (MT-RNR1) cause aminoglycoside-induced irreversible hearing loss. Mitochondrial DNA is usually not included in targeted sequencing experiments; however, off-target data may deliver this information. Here, we extract MT-RNR1 genetic variation, including the most relevant ototoxicity variant m.1555A>G, using the off-target reads of 473 research samples, sequenced through a capture-based, custom-targeted panel and whole exome sequencing (WES), and of 1245 diagnostic samples with clinical WES. Sanger sequencing and fluorescence-based genotyping were used for genotype validation. There was a correlation between off-target reads and mitochondrial coverage (r_customPanel = 0.39, p = 2 ×

SUBMITTER: Lanillos J 

PROVIDER: S-EPMC7408883 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature