Evolution Of Sequencing Technology For Genomics Applications

By Vijay Walia

Sequencing is the process of decoding deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). DNA is constantly replicated in all living cells as cell prepares for cell division, and is copied to transcribe RNA. These strategies are enabling researchers to understand how changes in DNA sequence regulate diseases and phenotypes. Since 2003, after the completion of the Human Genome project, significant progress has been made in sequencing. Sequencing technologies have revealed astonishing data over the last ten years for multiple species.

Fred Sanger published the dideoxy method that revolutionized the whole sequencing industry [2], after nearly 20 years of DNA structure discovery [1]. This method involves copying single strand DNA using dideoxynucleotides, which are chemically altered bases, allowing chain termination to occur as bases are incorporated, followed by resolving using capillary electrophoresis. During mid-1980, a number of improvements in Sanger sequencing, such as fluorometry-based detection and capillary-based electrophoresis, led to automated DNA sequencing machines. During the 1990’s, DNA sequencers were used in many laboratories for sequencing and played a significant role in Human Genome project, which was an international effort to decode the human genome over a 10 year period with billions of dollars of investment [3][4]. Since then many laboratories routinely use Sanger sequencers for identifying genetic variations. Although, the throughput of these sequencers is not sufficient for large-scale genomic studies, they still are a popular tool for denovo applications and smaller genomics studies.