ABSTRACT

This chapter describes the techniques and research strategies that are used during the sequencing phase of a genome project, when this ultimate objective is being directly addressed. It describes the strategies used to ensure that the master sequences are assembled correctly. The chapter examines how the challenges posed by sequence generation and assembly have been and are being met in the series of projects that have resulted in current understanding of the human genome. Over the years, a number of different methods for DNA sequencing have been developed, and others are likely to become important in the future. The techniques in use today can be divided into three categories: chain-termination method, short-read sequencing and long-read sequencing. More recently developed sequence assemblers take an alternative approach that is less computationally intensive and hence is applicable to short sequence reads.