دورية أكاديمية
A Novel Approach for the Identification of Pharmacogenetic Variants in MT-RNR1 through Next-Generation Sequencing Off-Target Data.
| العنوان: | A Novel Approach for the Identification of Pharmacogenetic Variants in MT-RNR1 through Next-Generation Sequencing Off-Target Data. |
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| المؤلفون: | Lanillos, Javier, Santos, María, Carcajona, Marta, Roldan-Romero, Juan María, Martinez, Angel M, Monteagudo, Maria, Leandro-García, Luis Javier, Maietta, Paolo, Alvarez, Sara, Rodriguez Antona, Cristina, Cascon Soriano, Alberto, Calsina, Bruna, Montero-Conde, Cristina, Robledo Batanero, Mercedes |
| المساهمون: | European Regional Development Fund, Fundación La Caixa |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute (MDPI) |
| سنة النشر: | 2020 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | RIBOSOMAL-RNA GENE, MITOCHONDRIAL 1555A-GREATER-THAN-G MUTATION, HEARING-LOSS, SUSCEPTIBILITY, DNA, PREVALENCE, HETEROPLASMY, PHENOTYPES, EXOME |
| الوصف: | 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. ; This work was supported by the project RTI2018-095039-B-I00 (MCI/AEI/FEDER, EU) and "la Caixa Foundation" INPhiNIT Retaining Doctorate Fellowship Programme (LCF/BQ/DR19/11740015). ; Sí |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.3390/jcm9072082Test; info:eu_repo/grantAgreement/ES/LCF/BQ/DR19/11740015; info:eu_repo/grantAgreement/ES/RTI2018-095039-B-I00; J Clin Med. 2020;9(7):2082.; http://hdl.handle.net/20.500.12105/11347Test; Journal of clinical medicine |
| DOI: | 10.3390/jcm9072082 |
| الإتاحة: | https://doi.org/20.500.12105/11347Test https://doi.org/10.3390/jcm9072082Test https://hdl.handle.net/20.500.12105/11347Test |
| حقوق: | http://creativecommons.org/licenses/by-nc-sa/4.0Test/ ; Atribución-NoComercial-CompartirIgual 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.45D54672 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/jcm9072082 |
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