Methods for genotyping polymorphisms in humans
Granted: December 8, 2009
Patent Number:
7629164
The invention provides nucleic acid sequences that are complementary, in one embodiment, to a collection of human single nucleotide polymorphisms. The invention provides the sequences in such a way as to make them available for a variety of analyses including genotyping a large number of SNPs in parallel by, for example, allele specific hybridization. The invention also provides a collection of human SNPs that is useful for genetic analysis within and across populations. As such, the…
Parallel preparation of high fidelity probes in an array format
Granted: June 16, 2009
Patent Number:
7547775
The present invention provides massively parallel oligonucleotide synthesis and purification for applications that utilize large collections of defined high-fidelity oligonucleotides (e.g., from about 101 to about 105 different sequences, generally between 25-160 bases in length).
Multiplex PCR
Granted: March 31, 2009
Patent Number:
7510829
Compositions and methods for nucleic acid amplification are provided that minimize the formation and amplification of spurious products, particularly in multiplex amplification reactions. Linear amplification molecules are provided. A first embodiment comprises a first common primer sequence, a first template homology region, a cleavable site, a second common primer sequence and a second template homology region. Methods employing the linear amplification molecules for nucleic acid…
Nucleic acid labeling methods
Granted: March 17, 2009
Patent Number:
7504215
In one aspect of the invention, a method is provided for end-labeling RNA (total RNA, mRNA, cRNA or fragmented RNA). In one aspect of the present invention, T4 RNA ligase is used to attach a 3?-labeled AMP or CMP donor to an RNA acceptor molecule. In another embodiment, a pyrophosphate molecule 3?-AppN-3?-linker-detectable moiety is used as donor molecule. In another aspect of the present invention, a method of detecting the presence of an RNA of interest in a sample is provided, the…
Nucleic acid labeling compounds
Granted: February 17, 2009
Patent Number:
7491818
Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.
Photocleavable protecting groups and methods for their use
Granted: December 30, 2008
Patent Number:
7470783
Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R1)(R2)—O—C(O)-wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative…
2-aminopyrimidin-4-one nucleic acid labeling compounds
Granted: December 23, 2008
Patent Number:
7468243
Nucleic acid labeling compounds are disclosed having the formula: These compounds are useful for attaching a detectable label to a nucleic acid.
Methods for genotyping selected polymorphism
Granted: December 2, 2008
Patent Number:
7459273
Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some…
Sequencing of surface immobilized polymers utilizing microfluorescence detection
Granted: December 2, 2008
Patent Number:
7459275
Means for simultaneous parallel sequence analysis of a large number of biological polymer macromolecules. Apparatus and methods may use fluorescent labels in repetitive chemistry to determine terminal monomers on solid phase immobilized polymers. Reagents which specifically recognize terminal monomers are used to label polymers at defined positions on a solid substrate.
Photoacid generators for the synthesis of oligo-DNA in a polymer matrix
Granted: November 18, 2008
Patent Number:
7452673
Compounds represented by the following structural formulas can be used as photoacid generators: Such compounds are useful, for example, in fabricating arrays of polymers.
Methods for genotyping with selective adaptor ligation
Granted: November 18, 2008
Patent Number:
7452671
The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. Selective adaptor ligation allows for selective…
System and method for programatic access to biological probe array data
Granted: November 11, 2008
Patent Number:
7451047
An applications programming interface is described that includes code libraries that enable transfer of pixel data, intermediate results data, or both, from a data structure or data file directly or indirectly to a user-provided application. The pixel data and intermediate results data may include data from biological experiments related probe arrays.
Nucleic acid labeling compounds
Granted: September 9, 2008
Patent Number:
7423143
Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.
System, method, and computer product for detection instrument calibration
Granted: July 29, 2008
Patent Number:
7406391
In one embodiment, a method of determining a drift value is described that includes performing one or more X-axis translations of an excitation beam over a probe array; measuring light responsive to the excitation beam from at least two positional reference elements associated with the probe array for the X-axis translations; calculating a distance value for the X-axis translation using a positional relationship of a known location associated with each of the positional reference…
Method of comparing a target nucleic acid and a reference nucleic acid
Granted: July 15, 2008
Patent Number:
7399584
The invention provides methods of comparing a target nucleic acid with a reference nucleic acid using nucleic acid arrays.
Methods of analysis of degraded nucleic acid samples
Granted: May 20, 2008
Patent Number:
7374927
The invention provides arrays for analysis of compromised nucleic acid samples, for example, nucleic acids obtained from formalin fixed paraffin embedded samples and methods to analyzed these compromised samples. Arrays are disclosed in which the probe selection region used to select probes for the array is the 300 bases of the target MRNA that are immediately upstream of the start of the poly(A) tail of the mRNA. The probes selected for the array are more biased toward the 3? end of the…
Modified nucleic acid probes
Granted: May 20, 2008
Patent Number:
7375198
Oligonucleotide analogue arrays attached to solid substrates and methods related to the use thereof are provided. The oligonucleotide analogues hybridize to nucleic acids with either higher or lower specificity than corresponding unmodified oligonucleotides. Target nucleic acids which comprise nucleotide analogues are bound to oligonucleotide and oligonucleotide analogue arrays.
Method and kits for multiplex hybridization assays
Granted: May 6, 2008
Patent Number:
7368242
The invention provides a method for genotyping interfering polymorphic loci in a target polynucleotide, such as a strand of genomic DNA, in a multiplex hybridization-based assay. The invention also provides nucleic acid standards for validating the performance of such hybridization-based assays. In one aspect, the method of the invention is carried out by providing for each interfering polymorphic locus one or more probes so that at least one probe is capable of forming a perfectly match…
Bioarray chip reaction apparatus and its manufacture
Granted: April 29, 2008
Patent Number:
7364895
A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.
Methods for genotyping polymorphisms in humans
Granted: April 22, 2008
Patent Number:
7361468
Methods, kits and arrays of nucleic acid probes for genotyping large numbers of human SNPs in parallel are provided. A set of more than 100,000 human SNPs, known to be biallelic in at least two populations is provided. Allele specific perfect match probes and genotyping probe sets are provided for each allele of each biallelic SNP in a set of human SNPs that is useful for genetic analysis within and across populations. Probe sets that include perfect match and mismatch probes are…
