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The human genome was sequenced from 1990 to 2003 using a combination of approaches. The original approach was to clone large pieces of chromosomes, then subclone them into fragments small enough to sequence; this is a clone-by-clone approach.

In the mid-1990s, whole genome shotgun sequencing was developed, in which chromosomes are randomly sheared into fragments and cloned. In the latter approach, a chromosome is fragmented differently each time, so each fragment generally overlaps with others, and these overlaps are used to reassemble the order of the fragments after they are sequenced.

Which of the following statements about whole genome shotgun sequencing and clone-by-clone genome sequencing is MOST correct?


Shotgun sequencing does not require mapping the locations of fragments prior to sequencing them.


Clone-by clone sequencing cannot be done by the Sanger method of DNA sequencing.


The method for amplifying DNA fragments for sequencing using the shotgun approach introduced more errors than the one used for the clone-by-clone approach.


Shotgun sequencing is more accurate when used for larger genomes than for smaller genomes.

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