Part I: Sequence Alignment

Current DNA sequencing methods can accurately determine only a few hundred ‘letters’ (bases) off each end of a contiguous stretch of DNA. It is therefore impossible to read a complete genome all at once. The human genome, for example, consists of about 3 billion base pairs — in contrast to about 500 that can be read at a time. The Whole Genome Shotgun Sequencing Method addresses this problem by randomly cutting multiple samples of identical DNA into small chunks, each of which is sequenced separately. If we were to cut up only a single DNA sample into many pieces, there would be no way of reconstructing the original sequence from the individual pieces. By cutting up multiple copies of the sequence in different ways, we can reconstruct the original sequence by aligning segments with overlapping reads, as illustrated in Fig. 1. Reads are asymmetric: They have an ‘outside’ end (where the DNA has been cut) and an ‘inside’ end (where the chunk of DNA continues but can’t be read). Reads can overlap in three ways (‘· · · ’ indicates the inside end of a read):