DNA Sequencing-by-Synthesis using Novel Nucleotide Analogs

The completion of the Human Genome Project has increased the need for highthroughput DNA sequencing technologies aimed at uncovering the genomic contributions to diseases. The DNA sequencing-by-synthesis (SBS) approach has shown great promise as a new platform for deciphering the genome. Recently, much progress has been made in the fundamental sciences required to make SBS a viable sequencing technology. One of the unique features of this approach is that many of the steps required are compatible in a modular fashion, allowing for the best solution at each stage to be effectively integrated. Recent advances include the design and synthesis of novel cleavable fluorescent nucleotide reversible terminators, DNA template preparation using emulsion polymerase chain reaction and clonal clusters on immobilized single DNA molecules, and new surface attachment chemistries for DNA template immobilization. The integration of these advances will lead to the development of a high-throughputDNAsequencing system based on SBS that is able to decipher an entire human genome for $1000 in the near future.