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Whole Genome Shotgun sequencing is a semi-automated DNA sequencing technique, in which high-molecular-weight DNA is sheared into random fragments, size selected (usually 2, 10, 50, and 150 kb), and cloned into an appropriate vector. The clones are then sequenced from both ends. The two ends of the same clone are referred to as mate pairs. The distance between two mate pairs can be inferred if the library size is known and has a narrow window of deviation. The sequences are aligned using sequence assembly software. Proponents of this approach argue that it is possible to sequence the whole genome at once using large arrays of sequencers, which makes the whole process much more efficient than the traditional approaches.

This article contains material from the NCBI Handbook published by the NCBI, which, as a US government publication, is in the public domain [1].

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