Patent ID: 7378245

Claim:
A method comprising: a) digesting reference and target DNA using a restriction endonuclease, wherein the restriction endonuclease digests the reference and the target DNA into different DNA fragments around one or more mutations that eliminates or creates a restriction site of the endonuclease, and mixing the reference and target DNA, thereby producing a digested mixture of reference and target DNA; b) labeling DNA strands of the digested mixture of reference and target DNA flanking the one or more mutations by one or more cycles of denaturation, annealing and labeling with a DNA polymerase, wherein denaturation and annealing allows annealing of the different DNA fragments around one or more mutations from reference and target DNA to form a partially double-stranded DNA duplex, and wherein the DNA polymerase labels the DNA of the partially double-stranded duplex by incorporating modified nucleotides into newly synthesized DNA, thereby producing a labeled mixture of reference and target DNA; c) hybridizing a combination of the labeled mixture of reference and target DNA and a labeled control DNA to at least one DNA array, which array comprises spots comprising at least one DNA probe, at least one of the spots comprising a DNA probe from the target DNA or the reference DNA or both, and wherein the labeled control DNA is (i) reference DNA alone or (ii) target DNA alone, treated substantially as in a) and b) but labeled with a distinguishable modified nucleotide; and (d) identifying the sequence of DNA of at least one spot of the DNA array that has significantly higher ratio of label signal from the mixture of reference and target DNA compared to label signal from the control DNA, thereby detecting and localizing one or more mutations in the target DNA as compared to the reference DNA.