Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays

A method for identifying a plurality of target nucleotide sequences in a sample, said method comprising:

• providing a sample potentially containing a plurality of target nucleotide sequences;
• providing a plurality of composite oligonucleotide probes characterized by having a target-specific portion coupled to a zip code portion, wherein the zip code portions of the composite oligonucleotide probes comprise a nucleotide sequence having greater than sixteen nucleotides that differs for each target-specific portion and hybridizes to their complements under uniform hybridization conditions, wherein the nucleotide sequence of a complement to one zip code portion differs from the nucleotide sequence of a complement to another zip code portion, when aligned to each other, by at least 25% of the nucleotides, to minimize cross-hybridization of one zip code portion to a complement of another zip code portion;
• attaching one or more labels to one or more of the plurality of composite oligonucleotide probes if their respective complementary target nucleotide sequences are present in the sample;
• providing a plurality of secondary oligonucleotide probes, each comprising a nucleotide sequence complementary to that of a zip code portion of the composite oligonucleotide probes, wherein each zip code portion hybridizes to its complementary secondary oligonucleotide probe in a base-specific manner;
• and
• detecting and distinguishing labeled products resulting from the hybridization of the target specific portions of the composite oligonucleotide probes to complementary target nucleotide sequences, if present, in the sample, and hybridization of the zip code portions of the composite oligonucleotide probes to their respective complementary secondary oligonucleotide probes, thereby identifying the presence of one or more target nucleotide sequences in the sample.