Quantification of rare allelic variants from pooled genomic DNA.
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.
Druley
Todd E
TE
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Vallania
Francesco L M
FL
Wegner
Daniel J
DJ
Varley
Katherine E
KE
Knowles
Olivia L
OL
Bonds
Jacqueline A
JA
Robison
Sarah W
SW
Doniger
Scott W
SW
Hamvas
Aaron
A
Cole
F Sessions
FS
Fay
Justin C
JC
Mitra
Robi D
RD
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
D004247:DNA