Sequencing DNA

In 1977 two methods for sequencing DNA were introduced. One method, referred to as Maxam-Gilbert sequencing, after the two scientists at Harvard University who developed the technique, uses different chemicals to break radioactively labeled DNA at specific base positions. The other approach, developed by Frederick Sanger in England and called the chain termination method (also called the Sanger method), uses a DNA synthesis reaction with special forms of the four nucleotides that, when added to a DNA chain, stop (terminate) further chain growth.

By either method, a collection of single-stranded DNA fragments is produced, each fragment one base longer than the next. The length of a fragment depends on where a chemical cleaved the strand (in Maxam-Gilbert sequencing) or where a special terminator base was added (in the chain termination method). The fragments are then separated according to their size by a process called gel electrophoresis, in which the fragments are drawn through a gel material by electric current, with shorter fragments migrating through the gel faster than longer fragments. The DNA sequence is then "read" by noting which reaction produced which fragment.