ARRAYS OF COMPLEMENTARY OLIGONUCLEOTIDES FOR ANALYZING THE HYBRIDIZATION BEHAVIOR OF NUCLEIC-ACIDS

Arrays of oligonucleotides corresponding to a full set of complements of a known sequence can be made in a single series of base couplings i n which each base in the complement is added in turn. Coupling is carr ied out on the surface of a solid support such as a glass plate, using a device which applies reagents in a defined area. The device is disp laced by a fixed movement after each coupling reaction so that consecu tive couplings overlap only a portion of previous ones. The shape and size of the device and the amount by which it is displaced at each ste p determines the length of the oligonucleotides. Certain shapes create arrays of oligonucleotides from mononucleotides up to a given length in a single series of couplings. The array is used in a hybridisation reaction to a labelled target sequence, and shows the hybridisation be haviour of every oligonucleotide in the target sequence with its compl ement in the array. Applications include sequence comparison to test f or mutation, analysis of secondary structure, and optimisation of PCR primer and antisense oligonucleotide design.