Chapter 10 – Application of Padlock and Selector Probes in Molecular Medicine

Padlock and selector probes are versatile tools that have been used and developed as great alternatives to molecular methods for the detection of nucleic acid sequences in the context of medicine. Their application has been proven to be useful in different areas from targeted sequencing, genotyping, and molecular diagnostics to the development of novel biosensors and techniques. This chapter describes the molecular functioning of these probes, in combination with DNA ligase-assisted specific circularization and isothermal rolling circle amplification, their properties, and their main applications in the field of medicine to date. It shows the potential of these approaches for developing assays that can be integrated into assays or instruments that will enable and improve access to information valuable for molecular medicine research and for improving medical diagnostics.

[1]  A. Wheeler,et al.  The Digital Revolution: A New Paradigm for Microfluidics , 2009 .

[2]  J. Tucker,et al.  Detection of DNA point mutations and mRNA expression levels by rolling circle amplification in individual cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  U. Landegren,et al.  Multiplex and quantifiable detection of nucleic acid from pathogenic fungi using padlock probes, generic real time PCR and specific suspension array readout. , 2009, Journal of microbiological methods.

[4]  David T. Okou,et al.  Microarray-based genomic selection for high-throughput resequencing , 2007, Nature Methods.

[5]  M. Stougaard,et al.  Detection of short repeated genomic sequences on metaphase chromosomes using padlock probes and target primed rolling circle DNA synthesis , 2007, BMC Molecular Biology.

[6]  Mats Nilsson,et al.  Rapid Identification of Bio-Molecules Applied for Detection of Biosecurity Agents Using Rolling Circle Amplification , 2012, PloS one.

[7]  P. Lizardi,et al.  Mutation detection and single-molecule counting using isothermal rolling-circle amplification , 1998, Nature Genetics.

[8]  Maria Strømme,et al.  Detection of rolling circle amplified DNA molecules using probe-tagged magnetic nanobeads in a portable AC susceptometer. , 2011, Biosensors & bioelectronics.

[9]  J. Bhak,et al.  New Lung Cancer Panel for High-Throughput Targeted Resequencing , 2014, Genomics & informatics.

[10]  Mostafa Ronaghi,et al.  Molecular inversion probe assay. , 2007, Methods in molecular biology.

[11]  R. Hogers,et al.  SNPWave: a flexible multiplexed SNP genotyping technology. , 2004, Nucleic acids research.

[12]  U. Landegren,et al.  Simultaneous Genotyping of All Hemagglutinin and Neuraminidase Subtypes of Avian Influenza Viruses by Use of Padlock Probes , 2008, Journal of Clinical Microbiology.

[13]  K. Lindblad-Toh,et al.  Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs , 2007, Nature Genetics.

[14]  U Landegren,et al.  A ligase-mediated gene detection technique. , 1988, Science.

[15]  Kin Fong Lei,et al.  Microfluidic Systems for Diagnostic Applications , 2012, Journal of laboratory automation.

[16]  M. Olivier A haplotype map of the human genome , 2003, Nature.

[17]  U. Landegren,et al.  PCR-generated padlock probes distinguish homologous chromosomes through quantitative fluorescence analysis , 2003, European Journal of Human Genetics.

[18]  M. Egholm,et al.  High accuracy genotyping directly from genomic DNA using a rolling circle amplification based assay , 2003, BMC Genomics.

[19]  D. Dressman,et al.  Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  U Landegren,et al.  Padlock probes: circularizing oligonucleotides for localized DNA detection. , 1994, Science.

[21]  A. Hurt,et al.  Detection of influenza A H1N1 and H3N2 mutations conferring resistance to oseltamivir using rolling circle amplification. , 2009, Antiviral research.

[22]  G. Gilbert,et al.  A practical method for subtyping of Streptococcus agalactiae serotype III, of human origin, using rolling circle amplification. , 2007, Journal of microbiological methods.

[23]  F. Maruyama,et al.  Quantitative Determination of Free-DNA Uptake in River Bacteria at the Single-Cell Level by In Situ Rolling-Circle Amplification , 2006, Applied and Environmental Microbiology.

[24]  U. Landegren,et al.  Analysis of T-cell receptor V beta gene repertoires after immune stimulation and in malignancy by use of padlock probes and microarrays. , 2005, Clinical chemistry.

[25]  Maria Strømme,et al.  Sensitive molecular diagnostics using volume-amplified magnetic nanobeads. , 2008, Nano letters.

[26]  Maria Strømme,et al.  Novel readout method for molecular diagnostic assays based on optical measurements of magnetic nanobead dynamics. , 2015, Analytical chemistry.

[27]  U. Landegren,et al.  Microarray-based molecular detection of foot-and-mouth disease, vesicular stomatitis and swine vesicular disease viruses, using padlock probes. , 2007, Journal of virological methods.

[28]  G. S. de Hoog,et al.  Rapid identification of fungal pathogens by rolling circle amplification using Fonsecaea as a model , 2011, Mycoses.

[29]  D. Clayton,et al.  A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region , 2006, Nature Genetics.

[30]  Jehyuk Lee,et al.  A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells , 2009, PLoS genetics.

[31]  Mats Nilsson,et al.  In situ mutation detection and visualization of intratumor heterogeneity for cancer research and diagnostics , 2013, Oncotarget.

[32]  G. Church,et al.  Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing , 2009, Science.

[33]  Huanming Yang,et al.  SNP detection for massively parallel whole-genome resequencing. , 2009, Genome research.

[34]  G. Weinstock,et al.  Direct selection of human genomic loci by microarray hybridization , 2007, Nature Methods.

[35]  U. Landegren,et al.  Parallel gene analysis with allele-specific padlock probes and tag microarrays. , 2003, Nucleic acids research.

[36]  Takehiko Kitamori,et al.  Microbead-based rolling circle amplification in a microchip for sensitive DNA detection. , 2010, Lab on a chip.

[37]  J. Shendure,et al.  Materials and Methods Som Text Figs. S1 and S2 Tables S1 to S4 References Accurate Multiplex Polony Sequencing of an Evolved Bacterial Genome , 2022 .

[38]  Jay Shendure,et al.  Multiplex amplification of large sets of human exons , 2007, Nature Methods.

[39]  Fredrik Dahl,et al.  MLGA—a rapid and cost-efficient assay for gene copy-number analysis , 2007, Nucleic acids research.

[40]  Ronald W. Davis,et al.  Allele quantification using molecular inversion probes (MIP) , 2005, Nucleic acids research.

[41]  C. Ramchand,et al.  Application of magnetic techniques in the field of drug discovery and biomedicine , 2003, Biomagnetic research and technology.

[42]  Ronald W. Davis,et al.  Connector Inversion Probe Technology: A Powerful One-Primer Multiplex DNA Amplification System for Numerous Scientific Applications , 2007, PLoS ONE.

[43]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[44]  Robert B. Hartlage,et al.  This PDF file includes: Materials and Methods , 2009 .

[45]  R. C. Novais,et al.  Molecular inversion probes for sensitive detection of Mycobacterium tuberculosis. , 2008, Journal of microbiological methods.

[46]  M F Hansen,et al.  Measurements of Brownian relaxation of magnetic nanobeads using planar Hall effect bridge sensors. , 2013, Biosensors & bioelectronics.

[47]  E. Mardis The impact of next-generation sequencing technology on genetics. , 2008, Trends in genetics : TIG.

[48]  M. F. Hansen,et al.  Turn-on optomagnetic bacterial DNA sequence detection using volume-amplified magnetic nanobeads. , 2015, Biosensors & bioelectronics.

[49]  M. Strømme,et al.  On-chip detection of rolling circle amplified DNA molecules from Bacillus globigii spores and Vibrio cholerae. , 2014, Small.

[50]  G. Kowalchuk,et al.  Quantitative multiplex detection of plant pathogens using a novel ligation probe-based system coupled with universal, high-throughput real-time PCR on OpenArrays™ , 2007, BMC Genomics.

[51]  Mats Nilsson,et al.  Colorimetric Nucleic Acid Testing Assay for RNA Virus Detection Based on Circle-to-Circle Amplification of Padlock Probes , 2011, Journal of Clinical Microbiology.

[52]  M. Nilsson,et al.  Highly specific DNA detection employing ligation on suspension bead array readout. , 2015, New biotechnology.

[53]  Takehiko Kitamori,et al.  Single-molecule DNA patterning and detection by padlock probing and rolling circle amplification in microchannels for analysis of small sample volumes. , 2011, Analytical chemistry.

[54]  Carolina Wählby,et al.  A single molecule array for digital targeted molecular analyses , 2008, Nucleic acids research.

[55]  Thomas A. Fleisher,et al.  Targeted NGS: A Cost-Effective Approach to Molecular Diagnosis of PIDs , 2014, Front. Immunol..

[56]  Yong Wang,et al.  Corrigendum: Genome sequencing in microfabricated high-density picolitre reactors , 2006, Nature.

[57]  Carolina Wählby,et al.  Single-cell A3243G Mitochondrial DNA Mutation Load Assays for Segregation Analysis , 2007, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[58]  S. Kingsmore,et al.  Comprehensive human genome amplification using multiple displacement amplification , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Erik L. McCarthy,et al.  Detection and identification of IHN and ISA viruses by isothermal DNA amplification in microcapillary tubes , 2006, Analytical and bioanalytical chemistry.

[60]  Toshihiro Tanaka The International HapMap Project , 2003, Nature.

[61]  Muhammad Akhtar Ali,et al.  In situ sequencing identifies TMPRSS2–ERG fusion transcripts, somatic point mutations and gene expression levels in prostate cancers , 2014, The Journal of pathology.

[62]  L. Moens,et al.  Diagnostics of Primary Immunodeficiency Diseases: A Sequencing Capture Approach , 2014, PloS one.

[63]  N. Saksena,et al.  Detection of the rapid emergence of the H275Y mutation associated with oseltamivir resistance in severe pandemic influenza virus A/H1N1 09 infections. , 2010, Antiviral research.

[64]  U. Landegren,et al.  In situ genotyping individual DNA molecules by target-primed rolling-circle amplification of padlock probes , 2004, Nature Methods.

[65]  U. Landegren,et al.  Enhanced detection and distinction of RNA by enzymatic probe ligation , 2000, Nature Biotechnology.

[66]  Mats Nilsson,et al.  A dual-tag microarray platform for high-performance nucleic acid and protein analyses , 2008, Nucleic acids research.

[67]  Mats Nilsson,et al.  Digital quantification using amplified single-molecule detection , 2006, Nature Methods.

[68]  L. Moens,et al.  HaloPlex Targeted Resequencing for Mutation Detection in Clinical Formalin-Fixed, Paraffin-Embedded Tumor Samples. , 2015, The Journal of molecular diagnostics : JMD.

[69]  J. Dahlberg,et al.  Structure-specific endonucleolytic cleavage of nucleic acids by eubacterial DNA polymerases. , 1993, Science.

[70]  Maria Strømme,et al.  Multiplex detection of DNA sequences using the volume-amplified magnetic nanobead detection assay. , 2009, Analytical chemistry.

[71]  M. Trau,et al.  Tunable nano/micropores for particle detection and discrimination: scanning ion occlusion spectroscopy. , 2010, Small.

[72]  Mais J. Jebrail,et al.  Digital microfluidics: a versatile tool for applications in chemistry, biology and medicine. , 2012, Lab on a chip.

[73]  U. Landegren,et al.  Padlock probes reveal single-nucleotide differences, parent of origin and in situ distribution of centromeric sequences in human chromosomes 13 and 21 , 1997, Nature Genetics.

[74]  Mats Nilsson,et al.  Gold Nanowire Based Electrical DNA Detection Using Rolling Circle Amplification , 2014, ACS nano.

[75]  Marcia M. Nizzari,et al.  Next-generation carrier screening , 2013, Genetics in Medicine.

[76]  Dongyu Liu,et al.  Rolling Circle DNA Synthesis: Small Circular Oligonucleotides as Efficient Templates for DNA Polymerases. , 1996, Journal of the American Chemical Society.

[77]  Charles Lee,et al.  Detection of Low-Copy-Number Genomic DNA Sequences in Individual Bacterial Cells by Using Peptide Nucleic Acid-Assisted Rolling-Circle Amplification and Fluorescence In Situ Hybridization , 2007, Applied and Environmental Microbiology.

[78]  Daniel Irimia,et al.  Ultrasensitive detection of low-abundance surface-marker protein using isothermal rolling circle amplification in a microfluidic nanoliter platform. , 2011, Small.

[79]  Joshua M. Korn,et al.  Mapping and sequencing of structural variation from eight human genomes , 2008, Nature.

[80]  C. H. Kim,et al.  Detection of infectious haematopoietic necrosis virus and infectious salmon anaemia virus by molecular padlock amplification. , 2006, Journal of fish diseases.

[81]  Kae Sato,et al.  Microfluidics-based in situ Padlock/Rolling Circle Amplification System for Counting Single DNA Molecules in a Cell , 2014, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[82]  George M. Church,et al.  Highly Multiplexed Subcellular RNA Sequencing in Situ , 2014, Science.

[83]  W. Barris,et al.  A Primary Assembly of a Bovine Haplotype Block Map Based on a 15,036-Single-Nucleotide Polymorphism Panel Genotyped in Holstein–Friesian Cattle , 2007, Genetics.

[84]  Yang Liu,et al.  tuberculosis detection via rolling circle amplification. , 2011, Analytical methods : advancing methods and applications.

[85]  P. Deyn,et al.  Mutations in ABCA7 in a Belgian cohort of Alzheimer's disease patients: a targeted resequencing study , 2015, The Lancet Neurology.

[86]  D. Y. Zhang,et al.  Amplification of target-specific, ligation-dependent circular probe. , 1998, Gene.

[87]  Jehyuk Lee,et al.  Digital RNA Allelotyping Reveals Tissue-specific and Allele-specific Gene Expression in Human , 2009, Nature Methods.

[88]  Carolina Wählby,et al.  In situ sequencing for RNA analysis in preserved tissue and cells , 2013, Nature Methods.

[89]  Steven Gallinger,et al.  Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24 , 2007, Nature Genetics.

[90]  J. Lammertyn,et al.  Circle-to-circle amplification on a digital microfluidic chip for amplified single molecule detection. , 2014, Lab on a chip.

[91]  D. Altshuler,et al.  Completing the map of human genetic variation , 2007, Nature.

[92]  K. Kinzler,et al.  Digital PCR. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[93]  David C. Thomas,et al.  Amplification of padlock probes for DNA diagnostics by cascade rolling circle amplification or the polymerase chain reaction. , 2009, Archives of pathology & laboratory medicine.

[94]  F. Maruyama,et al.  Visualization and Enumeration of Bacteria Carrying a Specific Gene Sequence by In Situ Rolling Circle Amplification , 2005, Applied and Environmental Microbiology.

[95]  Mats Nilsson,et al.  Homogeneous amplified single-molecule detection: Characterization of key parameters. , 2007, Analytical biochemistry.

[96]  G. Church,et al.  Accurate multiplex gene synthesis from programmable DNA microchips , 2004, Nature.

[97]  Magnus Isaksson,et al.  Targeted resequencing of candidate genes using selector probes , 2010, Nucleic Acids Res..

[98]  Jay Shendure,et al.  Polony DNA Sequencing , 2006, Current protocols in molecular biology.

[99]  Kae Sato,et al.  Bead-based padlock rolling circle amplification for single DNA molecule counting. , 2013, Analytical biochemistry.

[100]  A. Barbet,et al.  In Situ Detection of Anaplasma spp. by DNA Target-Primed Rolling-Circle Amplification of a Padlock Probe and Intracellular Colocalization with Immunofluorescently Labeled Host Cell von Willebrand Factor , 2008, Journal of Clinical Microbiology.

[101]  Andrew Collins,et al.  Detection of Alu sequences and mtDNA in comets using padlock probes. , 2006, Mutagenesis.

[102]  D. Andersson,et al.  A General Method for Rapid Determination of Antibiotic Susceptibility and Species in Bacterial Infections , 2014, Journal of Clinical Microbiology.

[103]  Maria Strømme,et al.  A magnetic nanobead-based bioassay provides sensitive detection of single- and biplex bacterial DNA using a portable AC susceptometer , 2013, Biotechnology journal.

[104]  U Landegren,et al.  PCR-generated padlock probes detect single nucleotide variation in genomic DNA. , 2000, Nucleic acids research.

[105]  G. S. de Hoog,et al.  Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification , 2014, PLoS neglected tropical diseases.

[106]  S. Hamilton-Dutoit,et al.  In situ detection of non-polyadenylated RNA molecules using Turtle Probes and target primed rolling circle PRINS , 2007, BMC biotechnology.

[107]  Madeleine P. Ball,et al.  Targeted and genome-scale methylomics reveals gene body signatures in human cell lines , 2009, Nature Biotechnology.

[108]  M. Strømme,et al.  Detection of Rifampicin Resistance in Mycobacterium tuberculosis by Padlock Probes and Magnetic Nanobead-Based Readout , 2013, PloS one.

[109]  Geoff R. Willmott,et al.  Quantitative sizing of nano/microparticles with a tunable elastomeric pore sensor. , 2011, Analytical chemistry.

[110]  Yi-Ping Ho,et al.  Detection of single enzymatic events in rare or single cells using microfluidics. , 2011, ACS nano.

[111]  U. Landegren,et al.  Signal amplification of padlock probes by rolling circle replication. , 1998, Nucleic acids research.

[112]  Fredrik Dahl,et al.  Circle-to-circle amplification for precise and sensitive DNA analysis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[113]  J. Meis,et al.  Identification and Typing of Isolates of Cyphellophora and Relatives by Use of Amplified Fragment Length Polymorphism and Rolling Circle Amplification , 2013, Journal of Clinical Microbiology.

[114]  J. Flanagan,et al.  RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. , 2012, The Journal of molecular diagnostics : JMD.

[115]  Charles Lee,et al.  Fluorescence-based detection of short DNA sequences under non-denaturing conditions. , 2008, Bioorganic & medicinal chemistry.

[116]  Henry A. Erlich,et al.  Amplification and analysis of DNA sequences in single human sperm and diploid cells , 1988, Nature.

[117]  Matthew D Dean,et al.  Linkage Disequilibrium in Wild Mice , 2007, PLoS genetics.

[118]  Roland Zengerle,et al.  Microfluidic platforms for lab-on-a-chip applications. , 2007, Lab on a chip.

[119]  Hanlee P. Ji,et al.  Multigene amplification and massively parallel sequencing for cancer mutation discovery , 2007, Proceedings of the National Academy of Sciences.

[120]  G. Kowalchuk,et al.  Robust Detection and Identification of Multiple Oomycetes and Fungi in Environmental Samples by Using a Novel Cleavable Padlock Probe-Based Ligation Detection Assay , 2009, Applied and Environmental Microbiology.

[121]  J. Blomberg,et al.  Detection of Rotavirus Using Padlock Probes and Rolling Circle Amplification , 2014, PloS one.

[122]  David F. Stern,et al.  In situ Detection of Specific DNA Double Strand Breaks using Rolling Circle Amplification , 2005, Cell cycle.

[123]  Phyllida Roe,et al.  Integration of DNA ligation and rolling circle amplification for the homogeneous, end-point detection of single nucleotide polymorphisms. , 2002, Nucleic acids research.

[124]  D C Ward,et al.  Visualization of oligonucleotide probes and point mutations in interphase nuclei and DNA fibers using rolling circle DNA amplification , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[125]  M. Nilsson,et al.  Digital quantification of rolling circle amplified single DNA molecules in a resistive pulse sensing nanopore. , 2015, Biosensors & bioelectronics.

[126]  Ola Söderberg,et al.  In situ detection and genotyping of individual mRNA molecules , 2010, Nature Methods.

[127]  J. Carpten,et al.  A comprehensive association study for genes in inflammation pathway provides support for their roles in prostate cancer risk in the CAPS study , 2006, The Prostate.

[128]  Thomas Schmidt,et al.  Homogeneous detection of single rolling circle replication products. , 2004, Analytical chemistry.

[129]  U. Landegren,et al.  RNA-templated DNA ligation for transcript analysis. , 2001, Nucleic acids research.

[130]  Erik L. McCarthy,et al.  Nucleic acid sensing by regenerable surface-associated isothermal rolling circle amplification. , 2007, Biosensors & bioelectronics.

[131]  T. Sorrell,et al.  Rapid Identification and Differentiation of Trichophyton Species, Based on Sequence Polymorphisms of the Ribosomal Internal Transcribed Spacer Regions, by Rolling-Circle Amplification , 2008, Journal of Clinical Microbiology.

[132]  Roger S Lasken,et al.  High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification , 2001, BMC Genomics.

[133]  Fuli Yu,et al.  Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay. , 2005, Genome research.

[134]  Ronald W. Davis,et al.  Multiplexed genotyping with sequence-tagged molecular inversion probes , 2003, Nature Biotechnology.

[135]  A. Fire,et al.  Rolling replication of short DNA circles. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[136]  Noritada Kaji,et al.  Rolling circle amplification and circle-to-circle amplification of a specific gene integrated with electrophoretic analysis on a single chip. , 2008, Analytical chemistry.