title: Quantification of rare allelic variants from pooled genomic DNA.
abstract: We report a targeted, cost-effective method to quantify rare single-nucleotide polymorphisms from pooled human genomic DNA using second-generation sequencing. We pooled DNA from 1,111 individuals and targeted four genes to identify rare germline variants. Our base-calling algorithm, SNPSeeker, derived from large deviation theory, detected single-nucleotide polymorphisms present at frequencies below the raw error rate of the sequencing platform.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Druley
authors.forename: Francesco L M
authors.initials: FL
authors.lastname: Vallania
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wegner
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Varley
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Knowles
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Bonds
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Robison
authors.forename: Scott W
authors.initials: SW
authors.lastname: Doniger
authors.forename: Aaron
authors.initials: A
authors.lastname: Hamvas
authors.forename: F Sessions
authors.initials: FS
authors.lastname: Cole
authors.forename: Justin C
authors.initials: JC
authors.lastname: Fay
authors.forename: Robi D
authors.initials: RD
authors.lastname: Mitra
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software
chemical_list: D004247:DNA