According to preferred methods of the invention the array of probes affixed to the substrate comprises a universal set of probes.
According to other preferred aspects of the invention at least two of the probes affixed to the substrate define overlapping sequences of the target nucleic acid sequence and more preferably at least two of the labelled probes define overlapping sequences of the target nucleic acid sequences.
In this case, sequence information about a fiagment may be determined in a simultaneous hybridization reaction with all of the arrayed probes.
In a process called SBH Format 1, nucleic add samples are arrayed, and labeled probes are hybridized with the samples.
Replica membranes with the same sets of sample nucleic acids may be used for parallel scoring of several probes and/or probes may be multiplexed.
In the present invention, SBH is applied to the efficient identification and sequencing of one or more nucleic acid samples.
The procedure has many applications in nucleic acid diagnostics, forensics, and gene mapping.
P OF THE INVENTION This invention relates in general to methods and apparatus for nucleic acid analysis, and, in particular, to methods and apparati for nucleic acid analysis.
BACKGROUND The rate of determining the sequence of the four nucleotides in nucleic acid samples is a majo T technical obstacle for further advancement of molecular biology, medicine, and biotechnology.
It also may be used to identify mutations responsible for genetic disorders and other traits, to assess biodiversity and to produce many other types of data dependent on nucleic acid sequence.
SUMMARY OF THE INVENTION The present invention provides a method for detecting a target nucleic acid species including the steps of providing an array of probes affixed to a substrate and a plurality of labeled probes wherein each labeled probe is selected to have a first nucleic acid sequence which is complementary to a first portion of a target nucleic acid and wherein the nucleic acid sequence of at least one probe affixed to the substrate is complementary to a second portion of the nucleic acid sequence of the target, the second portion being adjacent to the first portion; applying a target nucleic acid to the array under suitable conditions for hybridization of probe sequences to complementary sequences; introducing a labeled probe to the array; hybridizing a probe affixed to the substrate to the target nucleic acid; hybridizing the labeled probe to the target nucleic acid; affixing the labeled probe to an adjacently hybridized probe in the array; and detecting the labeled probe affixed to the probe in the array.
Sequence for the target nucleic acid may be assembled by uniquely overlapping scored oligonucleotides.
There are several approaches available to achieve sequencing by hybridization.
The process allows for sequencing long nucleic acid .fragments, e.g.