Universal base analogues and their applications in DNA sequencing technology

Universal base analogues are an important class of compounds which pair with all natural bases without discrimination. Since 1990s, a variety of compounds known as universal bases, including hypoxanthine, nitroazoles, isocarbostyril analogues, azole carboxamides and aromatic triazole analogues have been developed and employed in degenerate PCR primers, microarray probes, ligation and triplexes. There are a number of excellent reviews on the applications of universal base analogues in biochemistry and molecular biology, but their use in DNA sequencing has been overlooked, which was the original impetus for the authors to develop universal bases. In this manuscript, the status quo of universal base analogues and their applications in DNA sequencing are discussed, including Sanger sequencing, sequencing by hybridization, sequencing by ligation and sequencing by recognition tunneling. This should be of interest to those working in DNA sequencing technologies, molecular recognition and molecular biology.