WO1997037041A3 - Dna sequencing by mass spectrometry - Google Patents

Dna sequencing by mass spectrometry Download PDF

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Publication number
WO1997037041A3
WO1997037041A3 PCT/US1997/004394 US9704394W WO9737041A3 WO 1997037041 A3 WO1997037041 A3 WO 1997037041A3 US 9704394 W US9704394 W US 9704394W WO 9737041 A3 WO9737041 A3 WO 9737041A3
Authority
WO
WIPO (PCT)
Prior art keywords
mass spectrometry
chain
mass
nucleoside triphosphates
dna sequencing
Prior art date
Application number
PCT/US1997/004394
Other languages
French (fr)
Other versions
WO1997037041A9 (en
WO1997037041A2 (en
Inventor
Hubert Koester
Original Assignee
Sequenom Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/617,010 external-priority patent/US6194144B1/en
Application filed by Sequenom Inc filed Critical Sequenom Inc
Priority to AU22175/97A priority Critical patent/AU2217597A/en
Publication of WO1997037041A2 publication Critical patent/WO1997037041A2/en
Publication of WO1997037041A3 publication Critical patent/WO1997037041A3/en
Publication of WO1997037041A9 publication Critical patent/WO1997037041A9/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869Methods for sequencing
    • C12Q1/6872Methods for sequencing involving mass spectrometry

Abstract

The invention describes a new method to sequence DNA. The improvements over the existing DNA sequencing technologies are high speed, high throughput, no electrophoresis and gel reading artifacts due to the complete absence of an electrophoretic step, and no costly reagents involving various substitutions with stable isotopes. The invention utilizes the Sanger sequencing strategy and assembles the sequence information by analysis of the nested fragments obtained by base-specific chain termination via their different molecular masses using mass spectrometry, as for example, MALDI or ES mass spectrometry. A futher increase in throughtput can be obtained by introducing mass-modifications in the oligonucleotide primer, chain-terminating nucleoside triphosphates and/or in the chain-elongating nucleoside triphosphates, as well as using integrated tag sequences which allow multiplexing by hybridization of tag specific probes with mass differentiated molecular weights.
PCT/US1997/004394 1996-03-18 1997-03-18 Dna sequencing by mass spectrometry WO1997037041A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU22175/97A AU2217597A (en) 1996-03-18 1997-03-18 Dna sequencing by mass spectrometry

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US08/617,010 US6194144B1 (en) 1993-01-07 1996-03-18 DNA sequencing by mass spectrometry
US08/617,010 1996-03-18
US54783596A 1996-08-20 1996-08-20
US5/547,835 1996-08-20

Publications (3)

Publication Number Publication Date
WO1997037041A2 WO1997037041A2 (en) 1997-10-09
WO1997037041A3 true WO1997037041A3 (en) 1997-12-04
WO1997037041A9 WO1997037041A9 (en) 1997-12-31

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/004394 WO1997037041A2 (en) 1996-03-18 1997-03-18 Dna sequencing by mass spectrometry

Country Status (2)

Country Link
AU (1) AU2217597A (en)
WO (1) WO1997037041A2 (en)

Cited By (8)

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Publication number Priority date Publication date Assignee Title
US7820378B2 (en) 2002-11-27 2010-10-26 Sequenom, Inc. Fragmentation-based methods and systems for sequence variation detection and discovery
USRE44693E1 (en) 1996-11-06 2014-01-07 Sequenom, Inc. Beads bound to a solid support and to nucleic acids
US8962247B2 (en) 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
US8999266B2 (en) 2000-10-30 2015-04-07 Agena Bioscience, Inc. Method and apparatus for delivery of submicroliter volumes onto a substrate
US9012144B2 (en) 2003-11-12 2015-04-21 Fluidigm Corporation Short cycle methods for sequencing polynucleotides
US9249456B2 (en) 2004-03-26 2016-02-02 Agena Bioscience, Inc. Base specific cleavage of methylation-specific amplification products in combination with mass analysis
US9394565B2 (en) 2003-09-05 2016-07-19 Agena Bioscience, Inc. Allele-specific sequence variation analysis
US9540689B2 (en) 1998-05-01 2017-01-10 Life Technologies Corporation Method of determining the nucleotide sequence of oligonucleotides and DNA molecules

Families Citing this family (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2153387A1 (en) 1993-01-07 1994-07-21 Hubert Koester Dna sequencing by mass spectrometry
US6194144B1 (en) 1993-01-07 2001-02-27 Sequenom, Inc. DNA sequencing by mass spectrometry
US5605798A (en) 1993-01-07 1997-02-25 Sequenom, Inc. DNA diagnostic based on mass spectrometry
US6146854A (en) * 1995-08-31 2000-11-14 Sequenom, Inc. Filtration processes, kits and devices for isolating plasmids
US5777324A (en) 1996-09-19 1998-07-07 Sequenom, Inc. Method and apparatus for maldi analysis
US6207370B1 (en) 1997-09-02 2001-03-27 Sequenom, Inc. Diagnostics based on mass spectrometric detection of translated target polypeptides
CA2303790A1 (en) * 1997-09-15 1999-03-25 Brax Group Limited Characterising nucleic acid by mass spectrometry
US6268131B1 (en) * 1997-12-15 2001-07-31 Sequenom, Inc. Mass spectrometric methods for sequencing nucleic acids
US6780591B2 (en) 1998-05-01 2004-08-24 Arizona Board Of Regents Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
WO1999061910A1 (en) * 1998-05-26 1999-12-02 Board Of Trustees Of The University Of Illinois Screening of compounds using ultrafiltration and mass spectometry
US6218118B1 (en) 1998-07-09 2001-04-17 Agilent Technologies, Inc. Method and mixture reagents for analyzing the nucleotide sequence of nucleic acids by mass spectrometry
US6270976B1 (en) 1998-09-15 2001-08-07 Brax Group Limited Characterizing nucleic acid by mass spectrometry
DE19905082C1 (en) * 1999-01-29 2000-05-18 Epigenomics Gmbh Identification of methylation patterns of cytosine in genome DNA comprises chemical treatment to produce different base pairing behavior between cytosine and 5-methylcytosine
US6225061B1 (en) 1999-03-10 2001-05-01 Sequenom, Inc. Systems and methods for performing reactions in an unsealed environment
JP2002540402A (en) * 1999-03-18 2002-11-26 エクシコン エ/エス Use of LNA in mass spectrometry
US20020009394A1 (en) 1999-04-02 2002-01-24 Hubert Koster Automated process line
US7501245B2 (en) 1999-06-28 2009-03-10 Helicos Biosciences Corp. Methods and apparatuses for analyzing polynucleotide sequences
US7917301B1 (en) 2000-09-19 2011-03-29 Sequenom, Inc. Method and device for identifying a biological sample
KR20020064298A (en) 1999-10-13 2002-08-07 시쿼넘, 인코포레이티드 Methods for generating databases and databases for identifying polymorphic genetic markers
DE19963536C2 (en) * 1999-12-20 2003-04-10 Epigenomics Ag Procedure for the analysis of nucleic acid sequences
US20020009727A1 (en) * 2000-02-02 2002-01-24 Schultz Gary A. Detection of single nucleotide polymorphisms
GB0006141D0 (en) * 2000-03-14 2000-05-03 Brax Group Ltd Mass labels
US7666588B2 (en) 2001-03-02 2010-02-23 Ibis Biosciences, Inc. Methods for rapid forensic analysis of mitochondrial DNA and characterization of mitochondrial DNA heteroplasmy
WO2004060278A2 (en) * 2002-12-06 2004-07-22 Isis Pharmaceuticals, Inc. Methods for rapid identification of pathogens in humans and animals
US20030027135A1 (en) 2001-03-02 2003-02-06 Ecker David J. Method for rapid detection and identification of bioagents
US7226739B2 (en) 2001-03-02 2007-06-05 Isis Pharmaceuticals, Inc Methods for rapid detection and identification of bioagents in epidemiological and forensic investigations
US20040121313A1 (en) 2002-12-06 2004-06-24 Ecker David J. Methods for rapid detection and identification of bioagents in organs for transplantation
US20040121314A1 (en) 2002-12-06 2004-06-24 Ecker David J. Methods for rapid detection and identification of bioagents in containers
US20020155587A1 (en) 2001-04-20 2002-10-24 Sequenom, Inc. System and method for testing a biological sample
US7727713B2 (en) * 2001-06-20 2010-06-01 Nuevolution A/S Templated molecules and methods for using such molecules
US7217510B2 (en) 2001-06-26 2007-05-15 Isis Pharmaceuticals, Inc. Methods for providing bacterial bioagent characterizing information
WO2003036263A2 (en) 2001-10-26 2003-05-01 Sequenom, Inc. Method and apparatus for parallel dispensing of defined volumes of solid particles
DE10240746A1 (en) * 2002-09-01 2004-03-18 Epigenomics Ag Method for the detection of nucleic acid sequences using cleavable probe molecules
WO2004064972A2 (en) 2003-01-16 2004-08-05 Hk Pharmaceuticals, Inc. Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
DE10304219B3 (en) * 2003-01-30 2004-08-19 Epigenomics Ag Method for the detection of cytosine methylation patterns with high sensitivity
US7964343B2 (en) 2003-05-13 2011-06-21 Ibis Biosciences, Inc. Method for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US8158354B2 (en) 2003-05-13 2012-04-17 Ibis Biosciences, Inc. Methods for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture
US8097416B2 (en) 2003-09-11 2012-01-17 Ibis Biosciences, Inc. Methods for identification of sepsis-causing bacteria
US20120122096A1 (en) 2003-09-11 2012-05-17 Rangarajan Sampath Compositions for use in identification of bacteria
US8546082B2 (en) 2003-09-11 2013-10-01 Ibis Biosciences, Inc. Methods for identification of sepsis-causing bacteria
US8163895B2 (en) 2003-12-05 2012-04-24 Ibis Biosciences, Inc. Compositions for use in identification of orthopoxviruses
US7666592B2 (en) 2004-02-18 2010-02-23 Ibis Biosciences, Inc. Methods for concurrent identification and quantification of an unknown bioagent
EP2248911A1 (en) 2004-02-19 2010-11-10 Helicos Biosciences Corporation Methods and kits for analyzing polynucleotide sequences
EP2458619B1 (en) 2004-05-24 2017-08-02 Ibis Biosciences, Inc. Mass spectrometry with selective ion filtration by digital thresholding
US20050266411A1 (en) 2004-05-25 2005-12-01 Hofstadler Steven A Methods for rapid forensic analysis of mitochondrial DNA
US7811753B2 (en) 2004-07-14 2010-10-12 Ibis Biosciences, Inc. Methods for repairing degraded DNA
WO2006094238A2 (en) 2005-03-03 2006-09-08 Isis Pharmaceuticals, Inc. Compositions for use in identification of adventitious viruses
US8084207B2 (en) 2005-03-03 2011-12-27 Ibis Bioscience, Inc. Compositions for use in identification of papillomavirus
CA2616281C (en) 2005-07-21 2014-04-22 Isis Pharmaceuticals, Inc. Methods for rapid identification and quantitation of mitochondrial dna variants
US7666593B2 (en) 2005-08-26 2010-02-23 Helicos Biosciences Corporation Single molecule sequencing of captured nucleic acids
US8088582B2 (en) 2006-04-06 2012-01-03 Ibis Biosciences, Inc. Compositions for the use in identification of fungi
WO2007140417A2 (en) 2006-05-31 2007-12-06 Sequenom, Inc. Methods and compositions for the extraction and amplification of nucleic acid from a sample
AU2007353877B2 (en) 2006-09-14 2012-07-19 Ibis Biosciences, Inc. Targeted whole genome amplification method for identification of pathogens
US7902345B2 (en) 2006-12-05 2011-03-08 Sequenom, Inc. Detection and quantification of biomolecules using mass spectrometry
US8871471B2 (en) 2007-02-23 2014-10-28 Ibis Biosciences, Inc. Methods for rapid forensic DNA analysis
US9598724B2 (en) 2007-06-01 2017-03-21 Ibis Biosciences, Inc. Methods and compositions for multiple displacement amplification of nucleic acids
EP2195452B1 (en) 2007-08-29 2012-03-14 Sequenom, Inc. Methods and compositions for universal size-specific polymerase chain reaction
US20090180931A1 (en) 2007-09-17 2009-07-16 Sequenom, Inc. Integrated robotic sample transfer device
US9034580B2 (en) 2008-01-17 2015-05-19 Sequenom, Inc. Single molecule nucleic acid sequence analysis processes and compositions
WO2010033599A2 (en) 2008-09-16 2010-03-25 Ibis Biosciences, Inc. Mixing cartridges, mixing stations, and related kits, systems, and methods
AU2009293232B2 (en) 2008-09-16 2015-05-14 Sequenom Center For Molecular Medicine Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
US8476013B2 (en) 2008-09-16 2013-07-02 Sequenom, Inc. Processes and compositions for methylation-based acid enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
US8148163B2 (en) 2008-09-16 2012-04-03 Ibis Biosciences, Inc. Sample processing units, systems, and related methods
EP2344893B1 (en) 2008-09-16 2014-10-15 Ibis Biosciences, Inc. Microplate handling systems and methods
WO2010080616A1 (en) 2008-12-19 2010-07-15 Abbott Laboratories Molecular assay for diagnosis of malaria
EP2396803A4 (en) 2009-02-12 2016-10-26 Ibis Biosciences Inc Ionization probe assemblies
WO2010104798A1 (en) 2009-03-08 2010-09-16 Ibis Biosciences, Inc. Bioagent detection methods
WO2010114842A1 (en) 2009-03-30 2010-10-07 Ibis Biosciences, Inc. Bioagent detection systems, devices, and methods
EP3211095B1 (en) 2009-04-03 2019-01-02 Sequenom, Inc. Nucleic acid preparation compositions and methods
WO2011008971A1 (en) 2009-07-17 2011-01-20 Ibis Biosciences, Inc. Lift and mount apparatus
US9194877B2 (en) 2009-07-17 2015-11-24 Ibis Biosciences, Inc. Systems for bioagent indentification
US9416409B2 (en) 2009-07-31 2016-08-16 Ibis Biosciences, Inc. Capture primers and capture sequence linked solid supports for molecular diagnostic tests
EP2462244B1 (en) 2009-08-06 2016-07-20 Ibis Biosciences, Inc. Non-mass determined base compositions for nucleic acid detection
EP2957641B1 (en) 2009-10-15 2017-05-17 Ibis Biosciences, Inc. Multiple displacement amplification
US9926593B2 (en) 2009-12-22 2018-03-27 Sequenom, Inc. Processes and kits for identifying aneuploidy
US9758840B2 (en) 2010-03-14 2017-09-12 Ibis Biosciences, Inc. Parasite detection via endosymbiont detection
EP2710144B1 (en) 2011-05-19 2020-10-07 Agena Bioscience, Inc. Processes for multiplex nucleic acid identification
ES2930180T3 (en) 2012-03-02 2022-12-07 Sequenom Inc Methods for enriching for cancer nucleic acid from a biological sample
US9920361B2 (en) 2012-05-21 2018-03-20 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
US20140004105A1 (en) 2012-06-29 2014-01-02 Sequenom, Inc. Age-related macular degeneration diagnostics
CA2878979C (en) 2012-07-13 2021-09-14 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
CA2887094C (en) 2012-10-04 2021-09-07 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
EP3597774A1 (en) 2013-03-13 2020-01-22 Sequenom, Inc. Primers for dna methylation analysis
US10385401B2 (en) 2013-11-21 2019-08-20 Assistance Publique Hopitaux De Paris Method for detecting chromosomal rearrangements
EP3736344A1 (en) 2014-03-13 2020-11-11 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
CN107406882B (en) 2015-04-24 2022-03-01 基纳生物技术有限公司 Multiplexing method for identification and quantification of minor alleles and polymorphisms
CN107787371B (en) 2015-04-24 2022-02-01 基纳生物技术有限公司 Parallel method for detecting and quantifying minor variants
US10426424B2 (en) 2017-11-21 2019-10-01 General Electric Company System and method for generating and performing imaging protocol simulations
US20190367970A1 (en) 2018-06-01 2019-12-05 Agena Bioscience, Inc. Products and processes for nucleic acid detection and quantification
US20210301342A1 (en) 2018-09-07 2021-09-30 Sequenom, Inc. Methods, and systems to detect transplant rejection
WO2020172164A1 (en) 2019-02-19 2020-08-27 Sequenom, Inc. Compositions, methods, and systems to detect hematopoietic stem cell transplantation status
WO2021174079A2 (en) 2020-02-28 2021-09-02 Laboratory Corporation Of America Holdings Compositions, methods, and systems for paternity determination

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994016101A2 (en) * 1993-01-07 1994-07-21 Koester Hubert Dna sequencing by mass spectrometry
WO1994021822A1 (en) * 1993-03-19 1994-09-29 Sequenom, Inc. Dna sequencing by mass spectrometry via exonuclease degradation
WO1995014108A1 (en) * 1993-11-17 1995-05-26 Amersham International Plc Primer extension mass spectroscopy nucleic acid sequencing method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994016101A2 (en) * 1993-01-07 1994-07-21 Koester Hubert Dna sequencing by mass spectrometry
WO1994021822A1 (en) * 1993-03-19 1994-09-29 Sequenom, Inc. Dna sequencing by mass spectrometry via exonuclease degradation
WO1995014108A1 (en) * 1993-11-17 1995-05-26 Amersham International Plc Primer extension mass spectroscopy nucleic acid sequencing method

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
KIRPEKAR, F ET AL: "7-deazapurine bases offer a higher stability in the analysis of DNA by matrix-assisted laser desorption/ionization mass spectrometry", RAPID COMMUN. MASS SPECT., vol. 9, 1995, pages 525 - 31, XP002041458 *
NORDHOFF E ET AL: "Ion stability of nucleic acids in infrared matrix-assisted laser desorption/ionization mass specrtrmetry", NUCLEIC ACIDS RESEARCH, vol. 21, no. 15, 25 July 1993 (1993-07-25), pages 3347 - 57, XP000537440 *
SCHNEIDER K ET AL: "Increased stability of nucleic acids containing 7-deaza-guanosine and 7-deaza-adenosine may enable rapid DNA sequencing by matrix-assisted laser desorption spectroscopy", NUCLEIC ACIDS RESEARCH, vol. 23, no. 9, 11 May 1995 (1995-05-11), pages 1570 - 75, XP000601668 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE44693E1 (en) 1996-11-06 2014-01-07 Sequenom, Inc. Beads bound to a solid support and to nucleic acids
US9540689B2 (en) 1998-05-01 2017-01-10 Life Technologies Corporation Method of determining the nucleotide sequence of oligonucleotides and DNA molecules
US8999266B2 (en) 2000-10-30 2015-04-07 Agena Bioscience, Inc. Method and apparatus for delivery of submicroliter volumes onto a substrate
US7820378B2 (en) 2002-11-27 2010-10-26 Sequenom, Inc. Fragmentation-based methods and systems for sequence variation detection and discovery
US9394565B2 (en) 2003-09-05 2016-07-19 Agena Bioscience, Inc. Allele-specific sequence variation analysis
US9012144B2 (en) 2003-11-12 2015-04-21 Fluidigm Corporation Short cycle methods for sequencing polynucleotides
US9249456B2 (en) 2004-03-26 2016-02-02 Agena Bioscience, Inc. Base specific cleavage of methylation-specific amplification products in combination with mass analysis
US8962247B2 (en) 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses

Also Published As

Publication number Publication date
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WO1997037041A2 (en) 1997-10-09

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