A DNA sequencing strategy that requires only five bases of known terminal sequence for priming

Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10162-6. doi: 10.1073/pnas.92.22.10162.

Abstract

We have previously reported an enhanced version of sequencing by hybridization (SBH), termed positional SBH (PSBH). PSBH uses partially duplex probes containing single-stranded 3' overhangs, instead of simple single-stranded probes. Stacking interactions between the duplex probe and a single-stranded target allow us to reduce the probe sizes required to 5-base single-stranded overhangs. Here we demonstrate the use of PSBH to capture relatively long single-stranded DNA targets and perform standard solid-state Sanger sequencing on these primer-template complexes without ligation. Our results indicate that only 5 bases of known terminal sequence are required for priming. In addition, the partially duplex probes have the ability to capture their specific target from a mixture of five single-stranded targets with different 3'-terminal sequences. This indicates the potential utility of the PSBH approach to sequence mixtures of DNA targets without prior purification.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence*
  • DNA / chemistry*
  • DNA Primers / chemistry*
  • DNA, Single-Stranded / chemistry*
  • Genetic Techniques
  • Indicators and Reagents
  • Magnetics
  • Molecular Sequence Data
  • Polymerase Chain Reaction / methods

Substances

  • DNA Primers
  • DNA, Single-Stranded
  • Indicators and Reagents
  • DNA