2026-06-14T03:38:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/113472024-11-29T14:33:50Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
European Regional Development Fund
funder
Fundación La Caixa
2020-11-16T10:30:21Z
2020-11-16T10:30:21Z
2020-07-02
J Clin Med. 2020;9(7):2082.
10.3390/jcm9072082
Journal of clinical medicine
32630724
http://hdl.handle.net/20.500.12105/11347
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.
eng
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.
journal article
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
URL
https://repisalud.isciii.es/bitstreams/7dcba3de-8250-452c-9e9e-6e4fdaed4f0d/download
File
MD5
13152530e51cdd1316738606b41e655f
2419414
application/pdf
ANovelApproachfortheIdentification_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/0e863f5e-e0f7-44ca-9b0d-66bf42316811/download
File
MD5
fda6b28cdc46d8c8fbb77a39cb3d0edf
154773
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Copia de SuppTable1.xlsx
URL
https://repisalud.isciii.es/bitstreams/ea0f81c5-2278-4bd9-84c1-17986daefce1/download
File
MD5
9c53537d6fb6d4542a15535f750222df
281102
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Copia de SuppTable2.xlsx
URL
https://repisalud.isciii.es/bitstreams/2848fffb-756b-43f6-8e79-98fad46b05bb/download
File
MD5
9e9ffe23f2561ecd0750bed2c948b4cb
32326
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
Copia de SuppTable3.xlsx
URL
https://repisalud.isciii.es/bitstreams/a46cbed9-4ac2-4abb-a62e-4ec8be609917/download
File
MD5
6a870abc6753406cd5a0214373f85fca
51673
text/plain
ANovelApproachfortheIdentification_2020.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/db8bb925-ce0f-4312-97b5-be88b421b12d/download
File
MD5
2490f1fa31560b3fc49ed373eaac0b1a
100016
text/plain
Copia de SuppTable1.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/d4f182d6-6d40-435b-a6d9-c40457fcd5c8/download
File
MD5
a0bbea9a05078db75b0d13a553fda4ea
100000
text/plain
Copia de SuppTable2.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/819453e7-b733-45b4-8751-904f88b839dd/download
File
MD5
12985ffe568ce59f42f2e0e47278421a
17225
text/plain
Copia de SuppTable3.xlsx.txt