AU2004279810A1 - Single nucleotide polymorphism analysis of highly polymorphic target sequences - Google Patents
Single nucleotide polymorphism analysis of highly polymorphic target sequences Download PDFInfo
- Publication number
- AU2004279810A1 AU2004279810A1 AU2004279810A AU2004279810A AU2004279810A1 AU 2004279810 A1 AU2004279810 A1 AU 2004279810A1 AU 2004279810 A AU2004279810 A AU 2004279810A AU 2004279810 A AU2004279810 A AU 2004279810A AU 2004279810 A1 AU2004279810 A1 AU 2004279810A1
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- probe
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- nucleic acid
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- target
- Prior art date
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
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- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
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| US7205105B2 (en) * | 1999-12-08 | 2007-04-17 | Epoch Biosciences, Inc. | Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for PCR analysis |
| PL1687609T3 (pl) * | 2003-10-28 | 2015-05-29 | Epoch Biosciences Inc | Sondy fluoroscencyjne do wykrywania DNA przez hybrydyzację o ulepszonej czułości i niskim tle |
| EP1896602A4 (en) * | 2005-06-09 | 2009-08-12 | Epoch Biosciences Inc | IMPROVED AMPLIFICATION PROCESSES ON PRIMER BASIS |
| JP4713514B2 (ja) * | 2006-02-20 | 2011-06-29 | エフ.ホフマン−ラ ロシュ アーゲー | 改善された標識試薬 |
| US9677123B2 (en) | 2006-03-15 | 2017-06-13 | Siemens Healthcare Diagnostics Inc. | Degenerate nucleobase analogs |
| WO2008067002A2 (en) * | 2006-09-11 | 2008-06-05 | Southern Research Institute | Azole nucleosides and use as inhibitors of rna and dna varial polymerases |
| US8180572B2 (en) * | 2007-10-25 | 2012-05-15 | Canon U.S. Life Sciences, Inc. | High-resolution melting analysis |
| US9534255B2 (en) | 2008-12-17 | 2017-01-03 | Life Technologies Corporation | Methods, compositions, and kits for detecting allelic variants |
| WO2010111682A2 (en) | 2009-03-27 | 2010-09-30 | Life Technologies Corporation | Methods, compositions, and kits for detecting allelic variants |
| CA2756871A1 (en) | 2009-03-31 | 2010-10-07 | Arqule, Inc. | Substituted heterocyclic compounds |
| CN101659952B (zh) * | 2009-07-14 | 2012-07-18 | 上海之江生物科技有限公司 | 锁核酸和小沟结合物共修饰核酸片段 |
| AU2010324860A1 (en) * | 2009-11-25 | 2012-06-14 | Dharmacon, Inc. | Minor groove binder (MGB)-oligonucleotide miRNAs antagonists |
| WO2012097353A1 (en) * | 2011-01-14 | 2012-07-19 | Life Technologies Corporation | Methods, compositions, and kits for detecting rare cells |
| US9085800B2 (en) | 2011-03-23 | 2015-07-21 | Elitech Holding B.V. | Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use |
| US8969003B2 (en) | 2011-03-23 | 2015-03-03 | Elitech Holding B.V. | Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use |
| JP2013081448A (ja) * | 2011-05-02 | 2013-05-09 | Arkray Inc | 遺伝子変異検出用プローブ |
| US9677142B2 (en) | 2011-05-24 | 2017-06-13 | Elitechgroup B.V. | Detection of methicillin-resistant Staphylococcus aureus |
| WO2014159063A1 (en) | 2013-03-14 | 2014-10-02 | Elitech Holding B.V. | Functionalized 3-alkynyl pyrazolopyrimidine analogues as universal bases and methods of use |
| WO2014160046A1 (en) * | 2013-03-14 | 2014-10-02 | The Trustees Of The University Of Pennsylvania | A method for detecting mutations in single cells or single molecules |
| ES2654631T3 (es) | 2013-05-13 | 2018-02-14 | Elitechgroup B.V. | PCR digital en gotas con sondas cortas de ranura menor |
| RS59991B1 (sr) * | 2013-08-08 | 2020-04-30 | Scripps Research Inst | Metoda enzimskog in vitro obeležavanja specifičnog za položaj nukleinskih kiselina uvođenjem neprirodnih nukleotida |
| US10100349B2 (en) * | 2013-09-30 | 2018-10-16 | President And Fellows Of Harvard College | Methods of determining polymorphisms |
| GB201317355D0 (en) * | 2013-10-01 | 2013-11-13 | Epistem Ltd | Mutation Analysis |
| JP2017538418A (ja) | 2014-12-12 | 2017-12-28 | エリテックグループ・ベスローテン・フェンノートシャップElitechgroup B.V. | 抗生物質耐性細菌を検出する方法および組成物 |
| WO2016094162A1 (en) | 2014-12-12 | 2016-06-16 | Elitechgroup B.V. | Methods and compositions for detecting antibiotic resistant bacteria |
| NO344051B1 (en) * | 2017-05-04 | 2019-08-26 | Patogen As | Novel virus in Fish and Method for detection |
| IL271903B2 (en) | 2017-07-11 | 2025-04-01 | Synthorx Inc | Combination of unnatural nucleotides and methods therefor |
| SG11202000939PA (en) | 2017-08-03 | 2020-02-27 | Synthorx Inc | Cytokine conjugates for the treatment of proliferative and infectious diseases |
| US10677728B2 (en) | 2017-08-17 | 2020-06-09 | Elitechgroup B.V. | Duplex stabilizing fluorescence quenchers for nucleic acid probes |
| WO2019231617A1 (en) | 2018-05-29 | 2019-12-05 | Elitechgroup, Inc. | Carborhodamine compounds and methods of preparation thereof |
| EP3923974A4 (en) | 2019-02-06 | 2023-02-08 | Synthorx, Inc. | IL-2 CONJUGATES AND METHODS OF USE THEREOF |
| WO2021101145A1 (ko) * | 2019-11-19 | 2021-05-27 | 에스에프씨 주식회사 | 소광자 및 이의 용도 |
| EP4305192A4 (en) * | 2021-03-12 | 2025-04-09 | GT Molecular, Inc. | MULTIPLEXED GENOTYPE ASSAYS PERFORMED WITH A SINGLE PROBE USING FLUORESCENCE AMPLITUDE ADJUSTMENT |
| AU2022375767A1 (en) * | 2021-10-25 | 2024-05-02 | Gt Molecular, Inc. | Off-target blocking sequences to improve target discrimination by polymerase chain reaction |
| JP7276571B1 (ja) | 2022-06-20 | 2023-05-18 | 凸版印刷株式会社 | フラップエンドヌクレアーゼの蛍光基質における三重鎖構造の形成効率を向上させる方法 |
Family Cites Families (46)
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| US4458066A (en) * | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4358535A (en) * | 1980-12-08 | 1982-11-09 | Board Of Regents Of The University Of Washington | Specific DNA probes in diagnostic microbiology |
| US4711955A (en) * | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
| FR2540122B1 (fr) * | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US4883750A (en) * | 1984-12-13 | 1989-11-28 | Applied Biosystems, Inc. | Detection of specific sequences in nucleic acids |
| US4683195A (en) * | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4683202A (en) * | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4868105A (en) * | 1985-12-11 | 1989-09-19 | Chiron Corporation | Solution phase nucleic acid sandwich assay |
| US4800159A (en) * | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| US4868103A (en) * | 1986-02-19 | 1989-09-19 | Enzo Biochem, Inc. | Analyte detection by means of energy transfer |
| US6270961B1 (en) | 1987-04-01 | 2001-08-07 | Hyseq, Inc. | Methods and apparatus for DNA sequencing and DNA identification |
| US5202231A (en) * | 1987-04-01 | 1993-04-13 | Drmanac Radoje T | Method of sequencing of genomes by hybridization of oligonucleotide probes |
| US5525464A (en) * | 1987-04-01 | 1996-06-11 | Hyseq, Inc. | Method of sequencing by hybridization of oligonucleotide probes |
| US5124246A (en) * | 1987-10-15 | 1992-06-23 | Chiron Corporation | Nucleic acid multimers and amplified nucleic acid hybridization assays using same |
| CA1323293C (en) | 1987-12-11 | 1993-10-19 | Keith C. Backman | Assay using template-dependent nucleic acid probe reorganization |
| CA1341584C (en) | 1988-04-06 | 2008-11-18 | Bruce Wallace | Method of amplifying and detecting nucleic acid sequences |
| WO1990003370A1 (en) | 1988-09-28 | 1990-04-05 | Microprobe Corporation | DERIVATIVES OF PYRAZOLO[3,4-d]PYRIMIDINE |
| US5849482A (en) | 1988-09-28 | 1998-12-15 | Epoch Pharmaceuticals, Inc. | Crosslinking oligonucleotides |
| EP0472648A4 (en) | 1989-05-18 | 1992-09-16 | Microprobe Corporation | Crosslinking oligonucleotides |
| US5237101A (en) * | 1990-01-26 | 1993-08-17 | The Trustees Of The Univ. Of Penna. | Propargylic and allenic sulfones |
| WO1992000588A1 (fr) | 1990-07-02 | 1992-01-09 | Teijin Limited | Disque optique |
| US5210015A (en) * | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US5512667A (en) * | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
| AU2028792A (en) | 1991-05-17 | 1992-12-30 | Uab Research Foundation | Sequence specific dna binding drugs |
| US5419966A (en) * | 1991-06-10 | 1995-05-30 | Microprobe Corporation | Solid support for synthesis of 3'-tailed oligonucleotides |
| WO1993003736A1 (en) | 1991-08-21 | 1993-03-04 | Microprobe Corporation | Cross-linking oligonucleotides for enzyme-mediated triple strand formation |
| US5574142A (en) * | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
| WO1994017092A1 (en) | 1993-01-26 | 1994-08-04 | Microprobe Corporation | Bifunctional crosslinking oligonucleotides adapted for linking to a desired gene sequence of invading organism or cell |
| US5786138A (en) * | 1993-01-29 | 1998-07-28 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Hyperstabilizing antisense nucleic acid binding agents |
| US5446137B1 (en) * | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5646126A (en) * | 1994-02-28 | 1997-07-08 | Epoch Pharmaceuticals | Sterol modified oligonucleotide duplexes having anticancer activity |
| DE4408528A1 (de) | 1994-03-14 | 1995-09-28 | Hoechst Ag | Peptid-Oligonucleotid-Derivate, deren Herstellung und Verwendung |
| FR2719048B1 (fr) | 1994-04-25 | 1996-07-19 | Pasteur Strasbourg I Universit | Bases nucléiques polycationiques et oligonucléotides les contenant. |
| US5556752A (en) * | 1994-10-24 | 1996-09-17 | Affymetrix, Inc. | Surface-bound, unimolecular, double-stranded DNA |
| US5801155A (en) * | 1995-04-03 | 1998-09-01 | Epoch Pharmaceuticals, Inc. | Covalently linked oligonucleotide minor grove binder conjugates |
| US6312894B1 (en) * | 1995-04-03 | 2001-11-06 | Epoch Pharmaceuticals, Inc. | Hybridization and mismatch discrimination using oligonucleotides conjugated to minor groove binders |
| US5912340A (en) | 1995-10-04 | 1999-06-15 | Epoch Pharmaceuticals, Inc. | Selective binding complementary oligonucleotides |
| US5659022A (en) * | 1996-01-05 | 1997-08-19 | Epoch Pharmaceuticals, Inc. | Oligonucleotide-cyclopropapyrroloindole conjugates as sequence specific hybridization and crosslinking agents for nucleic acids |
| US5776907A (en) * | 1996-05-20 | 1998-07-07 | Texas Biotechnology Corporation | Mitomycin oligonucleotide conjugates |
| US5955590A (en) | 1996-07-15 | 1999-09-21 | Worcester Foundation For Biomedical Research | Conjugates of minor groove DNA binders with antisense oligonucleotides |
| WO1998018965A1 (en) * | 1996-10-29 | 1998-05-07 | University Of Nebraska At Lincoln | Method for detecting point mutations in dna utilizing fluorescence energy transfer |
| US7205105B2 (en) * | 1999-12-08 | 2007-04-17 | Epoch Biosciences, Inc. | Real-time linear detection probes: sensitive 5′-minor groove binder-containing probes for PCR analysis |
| US6579680B2 (en) * | 2000-02-28 | 2003-06-17 | Corning Incorporated | Method for label-free detection of hybridized DNA targets |
| ATE384731T1 (de) * | 2000-08-03 | 2008-02-15 | Hoffmann La Roche | Nukleinsäurebindende verbindungen mit pyrazolo 3, 4-d pyrimidinanalogen von purin-2,6-diamin und ihre verwendung |
| JP4709959B2 (ja) * | 2001-06-14 | 2011-06-29 | 国立大学法人東京工業大学 | ヌクレオシドホスホロアミダイト化合物 |
| DE10142643A1 (de) * | 2001-08-31 | 2003-04-24 | Clondiag Chip Tech Gmbh | Detektion von Wechselwirkungen auf Sonden-Arrays |
-
2004
- 2004-09-29 US US10/954,955 patent/US7348146B2/en not_active Expired - Lifetime
- 2004-09-30 EP EP04789416A patent/EP1670928A4/en not_active Withdrawn
- 2004-09-30 CA CA002540551A patent/CA2540551A1/en not_active Abandoned
- 2004-09-30 AU AU2004279810A patent/AU2004279810A1/en not_active Abandoned
- 2004-09-30 WO PCT/US2004/032265 patent/WO2005035545A2/en not_active Ceased
- 2004-09-30 JP JP2006534123A patent/JP2007510401A/ja active Pending
-
2008
- 2008-01-28 US US12/020,908 patent/US7718374B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005035545A3 (en) | 2005-07-28 |
| EP1670928A4 (en) | 2008-06-25 |
| US20050118623A1 (en) | 2005-06-02 |
| US7718374B2 (en) | 2010-05-18 |
| US20090087922A1 (en) | 2009-04-02 |
| US7348146B2 (en) | 2008-03-25 |
| EP1670928A2 (en) | 2006-06-21 |
| JP2007510401A (ja) | 2007-04-26 |
| WO2005035545A2 (en) | 2005-04-21 |
| CA2540551A1 (en) | 2005-04-21 |
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