The invention provides methods and kits for ordering sequence information
derived from one or more target polynucleotides. In one aspect, one or
more tiers or levels of fragmentation and aliquoting are generated, after
which sequence information is obtained from fragments in a final level or
tier. Each fragment in such final tier is from a particular aliquot,
which, in turn, is from a particular aliquot of a prior tier, and so on.
For every fragment of an aliquot in the final tier, the aliquots from
which it was derived at every prior tier is known, or can be discerned.
Thus, identical sequences from overlapping fragments from different
aliquots can be distinguished and grouped as being derived from the same
or different fragments from prior tiers. When the fragments in the final
tier are sequenced, overlapping sequence regions of fragments in
different aliquots are used to register the fragments so that
non-overlapping regions are ordered. In one aspect, this process is
carried out in a hierarchical fashion until the one or more target
polynucleotides are characterized, e.g. by their nucleic acid sequences,
or by an ordering of sequence segments, or by an ordering of single
nucleotide polymorphisms (SNPs), or the like.