title: Non optical semi-conductor next generation sequencing of the main cardiac QT-interval duration genes in pooled DNA samples.
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.
authors.affiliation: Genética Molecular-Laboratorio de Medicina-Fundación Renal (IRSIN-FRIAT), Hospital Universitario Central Asturias, 33006, Oviedo, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.forename: Julian R
authors.initials: JR
authors.lastname: Reguero
authors.forename: César
authors.initials: C
authors.lastname: Morís
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D006339:Heart Rate / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D060885:Multiplex Polymerase Chain Reaction; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human