Linked target capture

A method for detecting double stranded DNA insertion, the method comprising:

• ligating universal priming sites onto a plurality of duplex nucleic acid fragments wherein one or more of the plurality of duplex nucleic acid fragments comprise a tag sequence inserted at an insertion site;
• denaturing the plurality of ligated duplex nucleic acid fragments to create single stranded nucleic acid fragments comprising universal priming sites;
• exposing the single stranded nucleic acid fragments to
• a first plurality of linked capture probes each comprising a first target probe linked to a first universal primer, wherein the first target probe is complementary to the tag sequence and is blocked from extension, and
• a second plurality of linked capture probes each comprising a second target probe linked to a second universal primer, wherein the second target probe is complementary to a proximate sequence within 150 nucleotides of the insertion site and is blocked from extension,
• wherein the exposing step occurs under conditions that require binding of the first or the second target probe to its complementary target to permit binding of the respective linked universal primer to the universal priming site;
• extending the first and second universal primers to produce copies of the insertion site and the tag sequence region;
• and
• sequencing the copies to determine presence of the tag sequence in the insertion site.