Non Optical Semi-Conductor Next Generation Sequencing of the Main Cardiac QT-Interval Duration Genes in Pooled DNA Samples
DNA variants at the genes encoding cardiac channels have been associated with inherited arrhythmias and the QT interval in the general population. Next generation sequencing technologies would be of special interest to uncover the genetic variation at these genes. The amplification and sequencing of...
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| Published in: | Journal of cardiovascular translational research Vol. 7; no. 1; pp. 133 - 137 |
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| Format: | Journal Article |
| Language: | English |
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| Abstract | DNA variants at the genes encoding cardiac channels have been associated with inherited arrhythmias and the QT interval in the general population. Next generation sequencing technologies would be of special interest to uncover the genetic variation at these genes. The amplification and sequencing of DNA pools (instead of single individuals) would facilitate the rapid and cost-effective screening of large amounts of individuals. However, this pooling strategy could result in a signal of the rare variants below the detection capacity. To validate this approach, a pool of 20 individuals with known rare unique variants in five genes was amplified in only two tubes and sequenced using the non optical semi-conductor (
Ion Torrent PGM
, Life Technologies) technology. We show that this could be an effective strategy for the screening of large cohorts. Among others, this would facilitate the discovery of new sequence variants linked to cardiac arrhythmia in the general population. |
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| AbstractList | DNA variants at the genes encoding cardiac channels have been associated with inherited arrhythmias and the QT interval in the general population. Next generation sequencing technologies would be of special interest to uncover the genetic variation at these genes. The amplification and sequencing of DNA pools (instead of single individuals) would facilitate the rapid and cost-effective screening of large amounts of individuals. However, this pooling strategy could result in a signal of the rare variants below the detection capacity. To validate this approach, a pool of 20 individuals with known rare unique variants in five genes was amplified in only two tubes and sequenced using the non optical semi-conductor (Ion Torrent PGM, Life Technologies) technology. We show that this could be an effective strategy for the screening of large cohorts. Among others, this would facilitate the discovery of new sequence variants linked to cardiac arrhythmia in the general population. DNA variants at the genes encoding cardiac channels have been associated with inherited arrhythmias and the QT interval in the general population. Next generation sequencing technologies would be of special interest to uncover the genetic variation at these genes. The amplification and sequencing of DNA pools (instead of single individuals) would facilitate the rapid and cost-effective screening of large amounts of individuals. However, this pooling strategy could result in a signal of the rare variants below the detection capacity. To validate this approach, a pool of 20 individuals with known rare unique variants in five genes was amplified in only two tubes and sequenced using the non optical semi-conductor ( Ion Torrent PGM , Life Technologies) technology. We show that this could be an effective strategy for the screening of large cohorts. Among others, this would facilitate the discovery of new sequence variants linked to cardiac arrhythmia in the general population. |
| Author | Coto, Eliecer Gómez, Juan Morís, César Reguero, Julian R. Alvarez, Victoria |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24190697$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1038/nbt.2198 10.1126/science.1167728 10.1097/HCO.0b013e32835b0a41 10.1161/CIRCULATIONAHA.111.055947 10.1038/nature10242 10.1097/HCO.0b013e328352429d 10.1186/1471-2164-13-341 10.1161/01.CIR.0000014448.19052.4C 10.1007/s00109-003-0522-z 10.1002/humu.22184 10.7171/jbt.12-2301-003 10.1038/sj.ejhg.5201866 10.1186/alzrt137 10.1007/s12265-011-9263-5 10.1371/journal.pone.0067744 10.1111/j.1365-2796.2008.02026.x 10.1161/CIRCULATIONAHA.109.863076 |
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| References_xml | – volume: 30 start-page: 434 year: 2012 end-page: 9 ident: CR10 article-title: Performance comparison of benchtop high-throughput sequencing platforms publication-title: Nature Biotechnology doi: 10.1038/nbt.2198 contributor: fullname: Dallman – volume: 324 start-page: 387 year: 2009 end-page: 9 ident: CR15 article-title: Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes publication-title: Science doi: 10.1126/science.1167728 contributor: fullname: Riches – volume: 28 start-page: 63 year: 2013 end-page: 71 ident: CR4 article-title: Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise publication-title: Current Opinion in Cardiology doi: 10.1097/HCO.0b013e32835b0a41 contributor: fullname: Ackerman – volume: 125 start-page: 2027 year: 2012 end-page: 34 ident: CR2 article-title: Sudden cardiac death and genetic ion channelopathies: long QT, Brugada, short QT, catecholaminergic polymorphic ventricular tachycardia, and idiopathic ventricular fibrillation publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.111.055947 contributor: fullname: Monteforte – volume: 475 start-page: 348 year: 2011 end-page: 52 ident: CR9 article-title: An integrated semiconductor device enabling non-optical genome sequencing publication-title: Nature doi: 10.1038/nature10242 contributor: fullname: Rearick – volume: 27 start-page: 242 year: 2012 end-page: 52 ident: CR1 article-title: Genetics of ion-channel disorders publication-title: Current Opinion in Cardiology doi: 10.1097/HCO.0b013e328352429d contributor: fullname: Priori – volume: 13 start-page: 341 year: 2012 ident: CR11 article-title: A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers publication-title: BMC Genomics doi: 10.1186/1471-2164-13-341 contributor: fullname: Coupland – volume: 105 start-page: 1943 year: 2002 end-page: 8 ident: CR7 article-title: Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes publication-title: Circulation doi: 10.1161/01.CIR.0000014448.19052.4C contributor: fullname: Drolet – volume: 82 start-page: 182 year: 2004 end-page: 8 ident: CR8 article-title: Genetic variations of KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients publication-title: Journal of Molecular Medicine doi: 10.1007/s00109-003-0522-z contributor: fullname: Armstrong – volume: 34 start-page: 629 year: 2013 end-page: 35 ident: CR13 article-title: Nonoptical massive parallel DNA sequencing of BRCA1 and BRCA2 genes in a diagnostic setting publication-title: Human Mutation doi: 10.1002/humu.22184 contributor: fullname: Justino – volume: 23 start-page: 24 year: 2012 end-page: 30 ident: CR12 article-title: Rapid detection of the ACMG/ACOG-recommended 23 CFTR disease-causing mutations using ion torrent semiconductor sequencing publication-title: Journal of Biomolecular Techniques doi: 10.7171/jbt.12-2301-003 contributor: fullname: Moghis – volume: 15 start-page: 974 year: 2007 end-page: 9 ident: CR5 article-title: Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects publication-title: European Journal of Human Genetics doi: 10.1038/sj.ejhg.5201866 contributor: fullname: Chaouch – volume: 4 start-page: 34 year: 2012 ident: CR16 article-title: Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early onset and familial Alzheimer's disease Ibero-American cohort publication-title: Alzheimer's Research & Therapy doi: 10.1186/alzrt137 contributor: fullname: Cooper – volume: 4 start-page: 271 year: 2011 end-page: 80 ident: CR17 article-title: Genomic DNA pooling strategy for next-generation sequencing-based rare variant discovery in abdominal aortic aneurysm regions of interest-challenges and limitations publication-title: Journal of Cardiovascular Translational Research doi: 10.1007/s12265-011-9263-5 contributor: fullname: Medic – volume: 8 start-page: e67744 year: 2013 ident: CR14 article-title: Towards clinical molecular diagnosis of inherited cardiac conditions: a comparison of bench-top genome DNA sequencers publication-title: PLoS One doi: 10.1371/journal.pone.0067744 contributor: fullname: Wilkinson – volume: 265 start-page: 448 year: 2009 end-page: 58 ident: CR6 article-title: Common candidate gene variants are associated with QT interval duration in the general population publication-title: Journal of Internal Medicine doi: 10.1111/j.1365-2796.2008.02026.x contributor: fullname: Porthan – volume: 120 start-page: 1752 year: 2009 end-page: 60 ident: CR3 article-title: Genetic testing for long-QT syndrome: distinguishing pathogenic mutations from benign variants publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.109.863076 contributor: fullname: Salisbury |
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| Snippet | DNA variants at the genes encoding cardiac channels have been associated with inherited arrhythmias and the QT interval in the general population. Next... |
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| SubjectTerms | Biomedical Engineering and Bioengineering Biomedicine Cardiology Genetic Predisposition to Disease Genetic Testing - methods Genetic Variation Heart Rate - genetics High-Throughput Nucleotide Sequencing - methods Human Genetics Humans Long QT Syndrome - diagnosis Long QT Syndrome - genetics Long QT Syndrome - physiopathology Medicine Medicine & Public Health Multiplex Polymerase Chain Reaction NAV1.5 Voltage-Gated Sodium Channel - genetics Phenotype Potassium Channels, Voltage-Gated - genetics Predictive Value of Tests Reproducibility of Results |
| Title | Non Optical Semi-Conductor Next Generation Sequencing of the Main Cardiac QT-Interval Duration Genes in Pooled DNA Samples |
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