DNA Sequencing by Mass Spectrometry

Mass spectrometry has the potential to replace gel electrophoresis for fast DNA sequencing. In this tutorial paper, it is discussed how far mass spectrometry of DNA has come since the advent of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) and how much remains to be done before mass spectrometry will be a useful tool for DNA sequencing. A brief description of MALDI and ESI mass spectrometric analysis of DNA is presented along with the different strategies for DNA sequencing using mass spectrometry. These include mass spectrometric analysis to replace gel separation in Sanger sequencing, enzymatic ladder sequencing and sequencing by gas-phase fragmentation. The future role of mass spectrometry in DNA sequencing in the Human Genome Project and beyond is also discussed.