Effective Detection of Rare Variants in Pooled DNA Samples Using Cross-pool Tailcurve Analysis

Genome Biol. 2011 Sep 28;12(9):R93. doi: 10.1186/gb-2011-12-9-r93.


Sequencing targeted DNA regions in large samples is necessary to discover the full spectrum of rare variants. We report an effective Illumina sequencing strategy utilizing pooled samples with novel quality (Srfim) and filtering (SERVIC4E) algorithms. We sequenced 24 exons in two cohorts of 480 samples each, identifying 47 coding variants, including 30 present once per cohort. Validation by Sanger sequencing revealed an excellent combination of sensitivity and specificity for variant detection in pooled samples of both cohorts as compared to publicly available algorithms.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Algorithms*
  • Alleles
  • Cohort Studies
  • DNA / analysis
  • DNA / genetics*
  • Gene Frequency
  • Genome, Human
  • Genotype
  • Humans
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Sensitivity and Specificity
  • Sequence Alignment
  • Sequence Analysis, DNA / methods*
  • Sequence Analysis, DNA / standards
  • Software*


  • Adaptor Proteins, Signal Transducing
  • GRIP2 protein, human
  • Nerve Tissue Proteins
  • DNA