Quantification of rare allelic variants from pooled genomic DNA

Nat Methods. 2009 Apr;6(4):263-5. doi: 10.1038/nmeth.1307. Epub 2009 Mar 1.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Base Sequence
  • Chromosome Mapping / methods*
  • DNA / genetics*
  • Gene Frequency / genetics*
  • Genetic Variation / genetics*
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide / genetics*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Alignment / methods
  • Sequence Analysis, DNA / methods*
  • Software

Substances

  • DNA