2026-06-14T03:42:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/113472024-11-29T14:33:50Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Lanillos, Javier author Santos, María author Carcajona, Marta author Roldan-Romero, Juan María author Martinez, Angel M author Monteagudo, Maria author Leandro-García, Luis Javier author Maietta, Paolo author Alvarez, Sara author Rodriguez Antona, Cristina author Cascon Soriano, Alberto author Calsina, Bruna author Montero-Conde, Cristina author Robledo Batanero, Mercedes author 2020-07-02 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 (rcustomPanel = 0.39, p = 2 × 10-13 and rWES = 0.67, p = 7 × 10-21). The median read depth of MT-RNR1 m.1555 was similar to the average mitochondrial genome coverage, with saliva and blood samples giving comparable results. The genotypes from 415 samples, including three m.1555G carriers, were concordant with fluorescence-based genotyping data. In clinical WES, median MT-RNR1 coverage was 56×, with 90% of samples having ≥20 reads at m.1555 position, and one m.1494T and three m.1555G carriers were identified with no evidence for heteroplasmy. Altogether, this study shows that obtaining MT-RNR1 genotypes through off-target reads is an efficient strategy that can impulse preemptive pharmacogenetic screening of this mitochondrial gene. J Clin Med. 2020;9(7):2082. 10.3390/jcm9072082 Journal of clinical medicine 32630724 http://hdl.handle.net/20.500.12105/11347 RIBOSOMAL-RNA GENE MITOCHONDRIAL 1555A-GREATER-THAN-G MUTATION; HEARING-LOSS SUSCEPTIBILITY DNA PREVALENCE HETEROPLASMY PHENOTYPES EXOME A Novel Approach for the Identification of Pharmacogenetic Variants in MT-RNR1 through Next-Generation Sequencing Off-Target Data.