Whole Genome Shotgun Sequencing (WGS)

In contrast to the hierarchical BAC by BAC approach, which relies on the availability of genetic and physical maps for success, WGS is based on the strategy of sequencing a vast number of random genomic clones followed by intensive computer-based analysis of the DNA sequences which identifies matching sequences in different clones. This permits the assembly of a chromosomal DNA sequence, in principle without other map resources. As with the HS approach, overlapping clones are required, but since the clones are destined for direct sequence analysis, only vectors that contain small to medium inserts are normally used. Hence once the overlaps have been identified, the entire sequence is assembled. WGS was the approach adopted by the privately funded human genome initiative.
Although WGS remains somewhat controversial for sequencing complex genomes of ‘higher’ organisms because of the problems associated with repeat sequences and heterozygosity, it is a widely used approach. The number of complex genomes sequenced by this WGS is increasing and includes the fruit fly Drosophila, mosquito (anopheles), mouse, puffer fish, dog and grapevine. However, in some cases, such as the silk worm genome project, the WGS method has resulted in many seemingly irresolvable gaps in the genome and so the BAC-based hierarchical ordering of clones was used to close the gaps.Advances in computational analysis of WGS sequences suggest that the problems caused by repeat sequences could be overcome, hence the approach can be expected to gain more ground in future genome projects.