Abstract: In some embodiments, the present teachings provide compositions, systems, methods and kits for reducing the complexity of nucleotide sequences in a nucleic acid sample comprising the steps: hybridizing a plurality of polynucleotide constructs to at least one blocker oligonucleotide and to at least one capture oligonucleotide, wherein the plurality of polynucleotide constructs include a plurality of polynucleotides each joined to at least one nucleic acid adaptor, wherein the at least one nucleic acid adaptor can hybridize to the at least one blocker oligonucleotide, and wherein the at least one capture oligonucleotide can hybridize to at least a portion of target polynucleotides that are a sub-population of the plurality of polynucleotides, so as to produce a capture duplex.