Patent ID: 7033757

Claim:
A method of using a mutation scanning array to identify mutation in a target DNA sequence, wherein said mutation scanning array comprises a plurality of elements, wherein the elements contain immobilized oligonucleotides 8–50 bases long, that collectively span at least 5 different genes, wherein said method comprises: (a) hybridizing the target DNA sequence with a control DNA sequence wherein said control DNA sequence is the wild-type DNA sequence corresponding to the target DNA sequence to create a duplex, and wherein said target DNA comprises a pool of nucleotide segments that collectively span at least 5 different genes; (b) digesting the duplex to fragments of 50–300 base pairs, with restriction enzymes that allow generic addition of PCR primers; (c) adding PCR primers to the duplex (d) treating the duplex to remove any spontaneous aldehydes; (e) reacting the duplex with a repair glycosylase to convert any mismatched sites in the duplex to reactive sites containing an aldehyde-containing abasic site; (f) reacting the duplex with a compound of the formula X—Z—Y, wherein X is a detectable moiety, Y is NHNH2, O—NH2 or NH2, and Z is a hydrocarbon, alkyhydroxy, alkylethoxy, alkylester, alkylether, alkylamide or alkylamine, wherein Z may be substituted or unsubstituted; or where Z may contain a cleavable group; for a sufficient time and under conditions to covalently bind to the reactive sites; (g) detecting the bound compound to identify sites of mismatches; (h) isolating the DNA that contains mismatches from DNA without mismatches; (i) PCR-amplifying the mismatch-containing DNA (j) applying the mismatch-containing DNA on the Mutation Scanning Array, to determine the genomic position(s) where mismatches occur; and k) determining whether the mismatch is a mutation or polymorphism.