Gene sequencing: From Sanger sequencing to next generation sequencing

In the mid-70’s, a scientist called Fred Sanger developed a DNA sequencing method, eponymously known as Sanger sequencing, which revolutionised molecular biology.

Unravelling the genetic code allowed a vast breadth of scientific applications to take place, from basic science through to translational applications such as diagnostic testing and targeted drug therapy, and enabled the Human Genome Project.

Improvements over the years to Sanger’s original method allowed scientists to sequence sections of DNA up to around 600 bases in length. However, because scientists could only sequence one small section of DNA at once, the length of time, and cost, required to sequence whole genomes became a huge limiting factor.

Next generation sequencing (NGS) methods have since been developed which have solved this problem by allowing hundreds of thousands of fragments of DNA to be sequenced at the same time - known as massively parallel sequencing.

Fundamental to both Sanger sequencing and NGS is the principle of using the DNA to be sequenced as a template for DNA synthesis, reading which nucleotide is incorporated, and hence deducing the original complementary template sequence.

But the fact that you can read many fragments in parallel during NGS had transformed the speed of the sequencing, and hence its potential applications, both in the clinical and research settings.

Sequencing the human genome during the Human Genome Project using Sanger sequencing cost $1billion and took 6-8 years to complete. Using current NGS technologies it is possible to sequence an entire human genome in just 1-2 days at a cost of around $1000.

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In the 1970’s, Intel cofounder Gordon Moore noted that transistors were becoming smaller so fast that every two years twice as many could fit onto a computer chip. He used this observation to model the projected increase in computer processing power and speed, which became known as ‘Moore’s Law’.

During the era of Sanger sequencing, DNA sequencing costs and speed roughly followed Moore’s law, however with the advent of NGS technologies, the rate of progress increased exponentially, a dramatic deviation from Moore’s law, as shown below.

 Cost per Megabase of DNA Sequence