Fast, manual, nonradioactive method for DNA sequencing

Clin Chem. 1993 Aug;39(8):1682-5.

Abstract

We describe a protocol that allows nonradioactive detection of sequencing products after manual, direct, solid-phase sequencing of polymerase chain reaction-amplified DNA. The amplified DNA fragment to be studied is biotinylated at the 5' end of one of the two oligonucleotide primers used for amplification, allowing coupling to streptavidin-coated magnetic beads. The immobilized double-stranded DNA is then separated into single strands by alkaline treatment. A 5'-biotinylated sequencing primer is used after saturating with a biotin solution any possible remaining affinity sites on the streptavidin-coated magnetic beads. Sequencing is performed by using T7 DNA polymerase, and the sequencing products are electrophoresed in denaturing polyacrylamide sequencing gel. After transfer of the products to a nylon membrane, the sequencing pattern is revealed by chemiluminescence. Biotinylated alkaline phosphatase is bound to the 5' end of the sequencing primer via a streptavidin bridge and catalyzes the reaction by cleaving a phosphate group from a chemiluminescent substrate. The emitted photons are detected by exposing the membrane to x-ray film. This method is simple, rapid, and consistently successful and reproducible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Biotin
  • DNA, Neoplasm / chemistry*
  • DNA-Directed DNA Polymerase
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Luminescent Measurements
  • Magnetics
  • Microspheres
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA / methods*

Substances

  • DNA, Neoplasm
  • Biotin
  • bacteriophage T7 induced DNA polymerase
  • DNA-Directed DNA Polymerase