A method for enriching amplicons comprising a concatemer of at least two or more copies of a target polynucleotide, the method comprising: (a) generating a plurality of concatemers comprising a single-stranded polynucleotide from a circular target polynucleotide by multiple cycles of amplification with a first primer, wherein: (i) each cycle of the multiple cycles of amplification comprises denaturation at a denaturing temperature, primer annealing at an annealing temperature, and primer elongation at an elongation temperature, and wherein the generated plurality of concatemers contains a higher proportion of concatemers having at least two copies of the target polynucleotide as compared to a plurality of concatemers generated by utilizing one cycle of amplification under comparable conditions for denaturation and primer annealing but with an elongation time period comparable to a sum of the elongation time period of the multiple cycles; and (ii) wherein the first primer comprises a first 3' end that specifically hybridizes to the target polynucleotide via sequence complementarity and a first 5' end comprising a first common sequence that does not specifically hybridize to the target polynucleotide via sequence complementarity; (b) generating a plurality of extension products containing one or more copies of the target polynucleotide by extension of a second primer comprising a second 3' end that specifically hybridizes to the concatemer via sequence complementarity and a second 5' end comprising a second common sequence that does not specifically hybridize to the concatemer via sequence complementarity, wherein the first common sequence and the second common sequence each comprise at least 10 contiguous nucleotides at a 5'end and are at least 90% identical when optimally aligned; and (c) amplifying the plurality of extension products of step (b) under conditions to generate a plurality of amplicons, wherein the percentage of amplicons having two or more copies of the target polynucleotide is greater than the percentage of amplicons having fewer than two copies of the target polynucleotide, wherein the target polynucleotide has been derived from a sample obtained from a mammalian subject, and wherein the circular target polynucleotide is formed from a linear target polynucleotide using a ligase. (a) generating a plurality of concatemers comprising a single-stranded polynucleotide from a circular target polynucleotide by multiple cycles of amplification with a first primer, wherein: (i) each cycle of the multiple cycles of amplification comprises denaturation at a denaturing temperature, primer annealing at an annealing temperature, and primer elongation at an elongation temperature, and wherein the generated plurality of concatemers contains a higher proportion of concatemers having at least two copies of the target polynucleotide as compared to a plurality of concatemers generated by utilizing one cycle of amplification under comparable conditions for denaturation and primer annealing but with an elongation time period comparable to a sum of the elongation time period of the multiple cycles; and (ii) wherein the first primer comprises a first 3' end that specifically hybridizes to the target polynucleotide via sequence complementarity and a first 5' end comprising a first common sequence that does not specifically hybridize to the target polynucleotide via sequence complementarity; (i) each cycle of the multiple cycles of amplification comprises denaturation at a denaturing temperature, primer annealing at an annealing temperature, and primer elongation at an elongation temperature, and wherein the generated plurality of concatemers contains a higher proportion of concatemers having at least two copies of the target polynucleotide as compared to a plurality of concatemers generated by utilizing one cycle of amplification under comparable conditions for denaturation and primer annealing but with an elongation time period comparable to a sum of the elongation time period of the multiple cycles; and (ii) wherein the first primer comprises a first 3' end that specifically hybridizes to the target polynucleotide via sequence complementarity and a first 5' end comprising a first common sequence that does not specifically hybridize to the target polynucleotide via sequence complementarity; (b) generating a plurality of extension products containing one or more copies of the target polynucleotide by extension of a second primer comprising a second 3' end that specifically hybridizes to the concatemer via sequence complementarity and a second 5' end comprising a second common sequence that does not specifically hybridize to the concatemer via sequence complementarity, wherein the first common sequence and the second common sequence each comprise at least 10 contiguous nucleotides at a 5'end and are at least 90% identical when optimally aligned; and (c) amplifying the plurality of extension products of step (b) under conditions to generate a plurality of amplicons, wherein the percentage of amplicons having two or more copies of the target polynucleotide is greater than the percentage of amplicons having fewer than two copies of the target polynucleotide,