Patent ID: 8716190

Claim:
A method for amplifying a plurality of target sequences from a nucleic acid sample and analyzing the amplified target sequences, the method comprising: (a) fragmenting the nucleic acid sample to obtain target fragments comprising target sequences; (b) mixing the target fragments obtained in (a) with an array of probes arranged in features on a solid support, wherein each feature comprises multiple copies of a target specific array probe having a first probe region that is perfectly complementary to a first target region and a second probe region that is perfectly complementary to a second target region, wherein the first probe region is 5′ of the second probe region and wherein the first target region is 5′ of the second target region, and wherein the probes are attached to the solid support at the 5′ end of the probe, wherein target fragments hybridize to complementary target specific array probes to form probe:target fragment complexes wherein the target fragment hybridizes to the target specific array probe so that the first target region is hybridized to the first probe region and the second target region is hybridized to the second probe region; (c) joining a 5′ end of each target fragment to the 3′ end of the same target fragment by enzymatic ligation to form target circles wherein the 5′ end of each target fragment and the 3′ end of the same target fragment are joined by ligating the 5′ end of the target fragment to the 3′ end of an oligonucleotide and ligating the 3′ end of the target fragment to the 5′ end of the oligonucleotide and wherein the extended array probe comprises a plurality of copies of the complement of the oligonucleotide; (d) extending the array probes using the target circles as a template in a rolling circle amplification reaction, thereby obtaining extended array probes comprising a plurality of copies of the complement of a plurality of the target fragment; and (e) analyzing the copies.