Patent ID: 6872529

Claim:
A method of reducing the complexity of a first nucleic acid sample to produce a second nucleic acid sample comprising: fragmenting a first nucleic acid sample to produce double-stranded fragments; ligating one or more adaptors to the double-stranded fragments; digesting the adaptor ligated double-stranded fragments with an exonuclease that catalyzes the removal of mononucleotides from the 3′ termini of duplex DNA but not the 5′ termini or an exonuclease that catalyzes the removal of mononucleotides from the 5′ termini of duplex DNA but not the 3′ termini, wherein said exonuclease preferentially degrades duplex DNA, to produce single-stranded half molecules; adding a homopolymeric tail to the 3′ end of the single stranded half molecules, hybridizing a primer to the homopolymeric tail, and extending the primer to generate double-stranded half fragments from the single-stranded half molecules; amplifying a plurality of the double-stranded fragments by a polymerase chain reaction (PCR), and modulating the size of the amplified fragments by varying one or more reaction conditions or reagents to reduce the complexity of the first nucleic acid sample.