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Whilst I appreciate this is a large topic, what are the main differences between shotgun sequencing and clone based sequencing?

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Umm, you realize that an answer to this will be quite a few pages long right? Why don't you look up some of the common sequencing technologies on wikipedia and post a more specific question? – terdon May 13 '13 at 17:19
I have tried to make it a bit shorter. – James May 13 '13 at 18:21
up vote 5 down vote accepted

The v short answer is that in shotgun sequencing, the sequencer is fed a set of random sequences from the target. This can be done for instance by mechanically shearing DNA and then building a set of shotgun sequencing jobs which are then compiled back together by a genome assembler (i.e. in whole genome sequencing projects) into a full sequence.

In clone based sequencing, the DNA to be sequenced is specifically sectioned off into sequence copied into of plasmids (BACs - bacterial artificial chromosome) to divide the sequencing job into sections- a divide and conquer strategy. BACs can be 150 kb long just to give you an idea.

These are not mutually exclusive terms; clone-based sequencing projects usually use the large clone libraries to section the project into a set of shotgun sequencing projects.

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In short: the basis of the process is the same in both, the difference relies that in the clone based sequencing you make DNA library of the pieces of DNA clones you got from the sequence you used in first place. Like that, data management and the mounting of DNA contigs will be a lot easier computationally speaking. In shotgun sequencing the same is done but without the cloning and libraries, you directly mount contigs from sequenced sequence pieces, thus better computers are needed.

Also I think your terminology is wrong: shotgun strictly means the sequencing based on the random shearing and consecutive construction of contigs. I think you better mean whole genome shotgun sequencing with "shotgun sequencing"(as the clone based sequencing also is a shotgun sequencing method).

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