DNA-pools targeted-sequencing as a robust cost-effective method to detect rare variants: Application to dilated cardiomyopathy genetic diagnosis
| dc.rights.license | open | en_US |
| dc.contributor.author | PERRET, Claire | |
| dc.contributor.author | PROUST, Carole | |
| dc.contributor.author | ESSLINGER, Ulrike | |
| dc.contributor.author | ADER, Flavie | |
| dc.contributor.author | HAAS, Jan | |
| dc.contributor.author | PRUNY, Jean-Francois | |
| dc.contributor.author | ISNARD, Richard | |
| dc.contributor.author | RICHARD, Pascale | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | TREGOUET, David-Alexandre | |
| dc.contributor.author | CHARRON, Philippe | |
| dc.contributor.author | CAMBIEN, Francois | |
| dc.contributor.author | VILLARD, Eric | |
| dc.date.accessioned | 2024-01-16T16:00:47Z | |
| dc.date.available | 2024-01-16T16:00:47Z | |
| dc.date.issued | 2024-02 | |
| dc.identifier.issn | 1399-0004 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/187280 | |
| dc.description.abstractEn | Dilated cardiomyopathy (DCM) is a heart disease characterized by left ventricular dilatation and systolic dysfunction. In 30% of cases, pathogenic variants, essentially private to each patient, are identified in at least one of almost 50 reported genes. Thus, while costly, exons capture-based Next Generation Sequencing (NGS) of a targeted gene panel appears as the best strategy to genetically diagnose DCM. Here, we report a NGS strategy applied to pools of 8 DNAs from DCM patients and validate its robustness for rare variants detection at 4-fold reduced cost. Our pipeline uses Freebayes to detect variants with the expected 1/16 allele frequency. From the whole set of detected rare variants in 96 pools we set the variants quality parameters optimizing true positives calling. When compared to simplex DNA sequencing in a shared subset of 50 DNAs, 96% of SNVs/InsDel were accurately identified in pools. Extended to the 384 DNAs included in the study, we detected 100 variants (ACMG class 4 and 5), mostly in well-known morbid gene causing DCM such as TTN, MYH7, FLNC, and TNNT2. To conclude, we report an original pool-sequencing NGS method accurately detecting rare variants. This innovative approach is cost-effective for genetic diagnostic in rare diseases. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | cardiomyopathy | |
| dc.subject.en | DNAs-pool | |
| dc.subject.en | genetic diagnosis | |
| dc.subject.en | Next Generation Sequencing | |
| dc.title.en | DNA-pools targeted-sequencing as a robust cost-effective method to detect rare variants: Application to dilated cardiomyopathy genetic diagnosis | |
| dc.title.alternative | Clin Genet | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1111/cge.14427 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
| dc.identifier.pubmed | 37904629 | en_US |
| bordeaux.journal | Clinical Genetics | en_US |
| bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - UMR 1219 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.team | ELEANOR_BPH | en_US |
| bordeaux.team | BIOSTAT_BPH | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Clinical%20Genetics&rft.date=2024-02&rft.eissn=1399-0004&rft.issn=1399-0004&rft.au=PERRET,%20Claire&PROUST,%20Carole&ESSLINGER,%20Ulrike&ADER,%20Flavie&HAAS,%20Jan&rft.genre=article |
