Methods for targeted genomic analysis

A method for determining copy number of a specific genomic target region comprising:

• (a) hybridizing a tagged genomic library with a multifunctional capture probe module complex, wherein the multifunctional capture probe module selectively hybridizes to a specific genomic target region in the genomic library, and wherein the tagged genomic library comprises genomic DNA ligated to a multifunctional adaptor molecule comprising one or more nucleic acid tags, wherein the one or more nucleic acid tags identify a genomic DNA clone;
• (b) isolating the tagged genomic library-multifunctional capture probe module complex from a);
• (c) performing 3′-5′ exonuclease enzymatic processing on the isolated tagged genomic library-multifunctional capture probe module complex from b) using an enzyme with 3′-5′ exonuclease activity to remove the single stranded 3′ ends;
• (d) performing a PCR reaction on the enzymatically processed complex from c) wherein the tail portion of the multifunctional capture probe molecule is replicated in order to generate a hybrid nucleic acid molecule, wherein the hybrid nucleic acid molecule comprises the genomic target region capable of hybridizing to the multifunctional capture probe module and the complement of the multifunctional capture probe module tail sequence;
• (e) performing PCR amplification of the hybrid nucleic acid molecule in d);
• and
• (f) performing targeted genetic analysis on the hybrid nucleic acid molecule from e).

A method for targeted genetic analysis comprising:

• (a) hybridizing a tagged genomic library with a multifunctional capture probe hybrid module complex, wherein the multifunctional capture probe hybrid module selectively hybridizes to a specific genomic target region in the genomic library, and wherein the tagged genomic library comprises genomic DNA ligated to a multifunctional adaptor molecule comprising one or more nucleic acid tags, wherein the one or more nucleic acid tags identify a genomic DNA clone;
• (b) isolating the tagged genomic library-multifunctional capture probe hybrid module complex from a);
• (c) performing 5′ to 3′ DNA polymerase extension of the multifunctional capture probe on the complex from b) to replicate a region of the captured, tagged genomic target region that is 3′ of the multifunctional capture probe in order to generate a hybrid nucleic acid molecule, wherein the hybrid nucleic acid molecule comprises the multifunctional capture probe hybrid module and the complement of a region of the tagged genomic target region that is located in the 3′ direction from the location where the multifunctional capture probe hybrid module hybridizes to the genomic target region;
• and
• (d) performing targeted genetic analysis on the hybrid nucleic acid molecule from c).