Patent ID: 6403309
Filing Date: 2002-06-11
Classification: C12Q

Abstract:
A method for high-throughput nucleotide polymorphism identification in a nucleic acid sample from a subject comprising:(a) contacting a plurality of peptide-labeled polymorphism-specific oligonucleotide probes with the nucleic acid sample in solution, each probe containing a signal-generating marker, under conditions conducive to hybridization of the probes to nucleic acid in the sample, wherein different probes are labeled with distinguishable peptide labels; (b) contacting the probes with an addressable antibody array, said antibody array comprising a solid phase to which are attached antibodies immunospecific to said peptide labels; (c) removing probes that are not hybridized to nucleic acid from the sample; and (d) after steps (a), (b), and (c), detecting one or more probes that hybridize to nucleic acid in the sample by a method comprising, in the following order: i) detecting or measuring from the solid phase one or more signals generated where an antibody has bound to one of said peptide labels; ii) removing a marker on probes that are bound to the antibody array and that are hybridized with any mismatches to nucleic acid from the sample by contacting the hybrids with one or more enzymes which cleave at mismatched base parts; and iii) detecting or measuring from the solid phase one or more signals generated where an antibody has bound to one of said peptide labels, wherein, for each locus where an antibody has bound to one of said peptide labels, if the signal detected or measured in step (d)(i) differs from the signal detected or measured in step (d)(iii), then a nucleotide polymorphism is identified.