| 摘要 |
Disorders of the base sequences in genomic substances such as DNA and RNA are detected by changing the state of aggregation of fine particles by cleavaging using a nuclease. A single-stranded denatured product of the objective genomic substance is added to first and second fine particles each attached to plural pieces of first and second single-stranded nucleic acid probes, respectively. The first and second single-stranded nucleic acid probes are complementary to a first region and a second region, respectively, on the objective genomic substance, which are exclusive of each other and contiguous from each other. Aggregations of the first and second fine particles are formed by double or multiple hybridization reaction of the denatured objective genomic substance added with the first and second single-stranded nucleic acid probes. The aggregations are then digested with a nuclease which cleaves the non-complementary-mismatch-containing portion of the double strand of each hybrid permitting the formation of the aggregations, in the vicinity of a mismatch-localized region, but substantially not the completely complementary portion of the double strand of the hybrid. The size of the aggregations in the digested solution is first measured and then the degree of mismatch between the complementary base sequences of the objective genomic substance and the first or second single-stranded nucleic acid probe is measured using the size of the aggregations.
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