Skip to main content
Article thumbnail
Location of Repository

New Technologies for Genetic Analysis in Research and Diagnostics Settings

By Linda Strömqvist Meuzelaar

Abstract

This thesis work was designed to provide advanced technologies for the analysis of genetic variation, with emphasis upon complex genome exploration and DNA diagnostics.\ud For DNA sequence analysis, the work was based on Dynamic Allele-Specific Hybridization (DASH). DASH was originally developed for SNP genotyping via melt-curve analysis of allele-specific oligonucleotides. DASH was adapted for more general use in DNA diagnostics, and was demonstrated for mutation scanning of a 97 bp human genomic sequence and parallel detection of multiple mutations in the gyrA gene of Salmonella. Mutation scanning studies utilised a series of partially overlapping probes, where base substitutions were detected by alterations in the melting profile of the probes hybridising to each variant base.\ud Three SNPs in the target sequence were correctly detected in 16 samples. The mutation status of 62 Salmonella strains was accurately determined, using a combination of wildtype and mutation-specific probes. Work was also initiated to convert this concept to a microarray format, and to establish a platform for Thalassaemia diagnostics.\ud To facilitate highly parallel analyses, ‘MegaPlex PCR’ was developed for multiplex amplification of specific DNA fragments. This technology employs solid-phase PCR to capture many different targets and at the same time incorporate common primer sequences. Liquid-phase PCR is then used to amplify all products simultaneously, using a single primer pair. Innovations included the use of partly double-stranded surface-oligonucleotides (‘Barrier Oligos’) to enhance surface reactions, and the use of complex genomic DNA in native format and after pre-amplification. A final proof-of-principle study targeted 50-plex and 75-plex reactions to genotype human SNPs. Next-generation sequencing revealed that up to 86% of the targeted sequences were recovered and less than 10% of the amplified molecules were primer-dimers.\ud With further development, methods such as these should have substantial utility for improved DNA diagnostics and personalised medicine

Publisher: University of Leicester
Year: 2007
OAI identifier: oai:lra.le.ac.uk:2381/9238

Suggested articles

Citations

  1. (2007). A genome-wide association study identifies novel risk loci for type 2 diabetes.
  2. (2007). A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk.
  3. (2005). A genome-wide scalable SNP genotyping assay using microarray technology.
  4. (2005). A genotyping system capable of simultaneously analyzing >1000 single nucleotide polymorphisms in a haploid genome.
  5. (1998). A homogeneous fluorescence assay for PCR amplicons: its application to real-time, single-tube genotyping.
  6. (1998). A Homogeneous,
  7. (1988). A ligase-mediated gene detection technique.
  8. (1990). A primer guided nucleotide incorporation assay in the genotyping of apolipoprotein
  9. (2001). A rapid and reliable 7-deletion multiplex polymerase chain reaction assay for alpha -thalassemia.
  10. (1998). A Sequencing Method Based on Real-Time Pyrophosphate.
  11. (2002). A surface invasive cleavage assay for highly parallel SNP analysis.
  12. (2000). A System for Specific, High-throughput Genotyping by Allele-specific Primer Extension on Microarrays.
  13. (2004). A thalassaemia array for Southeast Asia.
  14. (2007). A versatile denaturing HPLC approach for human beta-globin gene mutation screening.
  15. (1996). Accessing genetic information with high-density DNA arrays.
  16. (2002). Accessing Single Nucleotide Polymorphisms in Genomic DNA by Direct Multiplex Polymerase Chain Reaction Amplification on Oligonucleotide Microarrays.
  17. (2004). Advanced sequencing technologies: methods and goals.
  18. (1989). Allele-Specific Enzymatic Amplification of beta-globin Genomic DNA for Diagnosis of Sickle Cell Anemia.
  19. (1999). Allelic discrimination using fluorogenic probes and the 5′ nuclease assay.
  20. (2003). Amplicon Melting Analysis with Labeled Primers: A Closed-Tube Method for Differentiating Homozygotes and Heterozygotes.
  21. (2007). An efficient method for multi-locus molecular haplotyping.
  22. (1989). Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS).
  23. (1994). Apolipoprotein E affects the rate of Alzheimer disease expression: beta-amyloid burden is a secondary consequence dependent on APOE genotype and duration of disease.
  24. (2003). Approaches to identify genes for complex human diseases: Lessons from Mendelian disorders.
  25. (2005). Array-based mutation detection of BRCA1 using direct probe/target hybridization.
  26. (2003). Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease.
  27. (2001). Association study designs for complex diseases.
  28. (2004). AutoDimer: a screening tool for primer-dimer and hairpin structures.
  29. (1998). Blind Analysis of Denaturing High-Performance Liquid Chromatography as a Tool for Mutation Detection.
  30. (2001). Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.
  31. (1996). Bridge Amplification: A Solid Phase
  32. (2004). Closed-Tube Genotyping with Unlabeled Oligonucleotide Probes and a Saturating DNA Dye.
  33. (1997). Colorimetric detection of immobilised PCR products generated on a solid support.
  34. (2002). Comparison of gyrA Mutations, Cyclohexane Resistance, and the Presence of Class I Integrons in Salmonella enterica from Farm Animals in England and Wales.
  35. (2005). Complete Gene Scanning by Temperature Gradient Capillary Electrophoresis Using the Cystic Fibrosis Transmembrane Conductance Regulator Gene as a Model.
  36. (1997). Covalent Attachment of DNA to Silicon Wafers for Analysis by MALDI-TOF Mass Spectrometry.
  37. (2002). Creating arrays by centrifugation.
  38. (1988). Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification.
  39. (1990). Detecting base pair substitutions in DNA fragments by temperature-gradient gel electrophoresis.
  40. (1987). Detection and localization of single base changes by denaturing gradient gel electrophoresis.
  41. (2002). Detection of gyrA Mutations in Quinolone-Resistant Salmonella enterica by Denaturing High-Performance Liquid Chromatography.
  42. (1996). Detection of immobilized amplicons by ELISA-like techniques.
  43. (2004). Detection of large-scale variation in the human genome.
  44. (1997). Detection of Numerous Y Chromosome Biallelic Polymorphisms by Denaturing High-Performance Liquid Chromatography. Genome Res.
  45. (1989). Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms.
  46. (2001). Detection of Single Base Alterations in Genomic DNA by Solid Phase Polymerase Chain Reaction on Oligonucleotide Microarrays.
  47. (1979). Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure.
  48. (2004). Development and Validation of a Diagnostic DNA Microarray To Detect Quinolone-Resistant Escherichia coli among Clinical Isolates.
  49. (2006). Development of a Real-Time PCR Assay for Detection of gyrA Mutations Associated with Reduced Susceptibility to Ciprofloxacin
  50. (2004). DFold: PCR design that minimizes secondary structure and optimizes downstream genotyping applications.
  51. (2006). Direct amplification of single-stranded DNA for pyrosequencing using linearafter-the-exponential (LATE)–PCR.
  52. (2005). DNA analysis with multiplex microarrayenhanced PCR.
  53. (2007). DNA Diagnostics by Surface-Bound Melt-Curve Reactions.
  54. (1999). DNA diagnostics: goals and Challenges.
  55. (1983). DNA fragments differing by single base-pair substitutions are separated in denaturing gradient gels: correspondence with melting theory.
  56. (2001). DNA Melting Analysis for Detection of Single Nucleotide Polymorphisms.
  57. (1977). DNA Sequencing with Chain-Terminating Inhibitors.
  58. (2005). dnaMATE: a consensus melting temperature prediction server for short DNA sequences.
  59. (1999). Dynamic allele-specific hybridization.
  60. (2004). Effects of Sodium Ions on DNA Duplex Oligomers: Improved Predictions of Melting Temperatures.
  61. (2005). Emerging technologies in DNA sequencing.
  62. (2001). Enabling Large-Scale Pharmacogenetic Studies by High-Throughput Mutation Detection and Genotyping Technologies.
  63. (2004). Encoded evidence: DNA in forensic analysis.
  64. (1967). Energy transfer: a spectroscopic ruler.
  65. (2003). Enhanced allele-specific PCR discrimination in SNP genotyping using 3' locked nucleic acid (LNA) primers.
  66. (1985). Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.
  67. (1990). Fast multiplex polymerase chain reaction on boiled clinical samples for rapid viral diagnosis.
  68. (2005). Fine-scale structural variation of the human genome.
  69. (2001). Fluorescein-Labeled Oligonucleotides for Real-Time PCR: Using the Inherent Quenching of Deoxyguanosine Nucleotides.
  70. (2003). Fluorescent in situ sequencing on polymerase colonies.
  71. (1996). fluorescent, solid-phase minisequencing for efficient screening of DNA sequence variation.
  72. (1985). Forensic application of DNA 'fingerprints'.
  73. (2005). Four-color DNA sequencing by synthesis on a chip using photocleavable fluorescent nucleotides.
  74. (2006). Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators.
  75. (2000). Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays.
  76. (1989). Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes.
  77. (2007). Genetic determinants of hair, eye and skin pigmentation in Europeans.
  78. (2007). Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.
  79. (2002). Genome architecture, rearrangements and genomic disorders.
  80. (2004). Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome.
  81. (2005). Genome sequencing in microfabricated high-density picolitre reactors.
  82. (2007). Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24.
  83. (2005). Genome-wide strategies for detecting multiple loci that influence complex diseases.
  84. (2004). Genotyping of Single-Nucleotide Polymorphisms by High-Resolution Melting of Small Amplicons.
  85. (2004). Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays.
  86. (1998). Global Epidemiology of Hemoglobin Disorders.
  87. (2006). Global variation in copy number in the human genome.
  88. (2001). Haplotype tagging for the identification of common disease genes.
  89. (2005). HapMap Consortium. A haplotype map of the human genome.
  90. (2003). HapMap Consortium. The International HapMap Project.
  91. (2007). HbVar database of human hemoglobin variants and thalassemia mutations:
  92. (1994). High-density multiplex detection of nucleic acid sequences: oligonucleotide ligation assay and sequence-coded separation.
  93. (2003). High-Resolution Genotyping by Amplicon Melting Analysis Using LCGreen.
  94. (2007). High-resolution melting assay for the detection of gyrA mutations causing quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi. Diagn Microbiol Infect Dis.
  95. (2005). High-Throughput Mitochondrial Genome Screening Method for Nonmelanoma Skin Cancer Using Multiplexed Temperature Gradient Capillary Electrophoresis.
  96. (2003). High-throughput single strand conformation polymorphism mutation detection by automated capillary array electrophoresis: validation of the method.
  97. (1999). High-throughput single-strand conformation polymorphism analysis by automated capillary electrophoresis: Robust multiplex analysis and pattern-based identification of allelic variants.
  98. (2005). High-throughput single-strand conformation polymorphism analysis on a microfabricated capillary array electrophoresis device.
  99. (2005). High-throughput SNP genotyping on universal bead arrays.
  100. (2005). Highly multiplexed molecular inversion probe genotyping: Over 10,000 targeted SNPs genotyped in a single tube assay.
  101. (2002). Homogeneous Amplification and Mutation Scanning of the p53 Gene Using Fluorescent Melting Curves.
  102. (1998). Homogeneous Multiplex Genotyping of Hemochromatosis Mutations with Fluorescent Hybridization Probes.
  103. (2006). Homogeneous PCR nucleobase quenching assays to detect four mutations that cause neuronal ceroid lipofuscinosis:
  104. (2004). Homogeneous Polymerase Chain Reaction Nucleobase Quenching Assay to Detect the 1-kbp Deletion in CLN3 That Causes Batten Disease.
  105. (2001). Hundredfold productivity of genome analysis by introduction of microtemperature-gradient gel electrophoresis.
  106. (1993). Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing.
  107. (2002). iFRET: An Improved Fluorescence System for DNAMelting Analysis. Genome Res.
  108. (1985). Individual-specific 'fingerprints'.
  109. (2003). Inheritance and Drug Response.
  110. (2001). Initial sequencing and analysis of the human genome.
  111. (1997). Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups.
  112. (2002). Integrated platform for detection of DNA sequence variants using capillary array electrophoresis.
  113. (2001). Integration of Multiple PCR Amplifications and DNA Mutation Analyses by Using Oligonucleotide Microchip.
  114. (2006). Interrogation of genomes by molecular copy-number counting (MCC).
  115. (2001). Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease.
  116. (2003). Large-Scale Association Studies of Variants
  117. (2004). Large-Scale Copy Number Polymorphism in the Human Genome.
  118. (2003). Large-scale genotyping of complex DNA.
  119. (1998). Large-scale identification, mapping, and genotyping of singlenucleotide polymorphisms in the human genome.
  120. (2003). LightCycler gyrA mutation assay (GAMA) identifies heterogeneity in GyrA in Salmonella enterica serotypes Typhi and Paratyphi A with decreased susceptibility to ciprofloxacin.
  121. (2004). Linear-After-The-Exponential (LATE)-PCR: An advanced method of asymmetric PCR and its uses in quantitative real-time analysis.
  122. (2005). Linear-After-The-Exponential (LATE)-PCR: Primer design criteria for high yields of specific single-stranded DNA and improved realtime detection.
  123. (2001). Linkage disequilibrium in the human genome.
  124. (2002). Making ends meet in genetic analysis using padlock probes.
  125. (2004). MARA: a novel approach for highly multiplexed locus-specific SNP genotyping using high-density DNA oligonucleotide arrays.
  126. (2005). Mechanisms of quinolone resistance in Escherichia coli and Salmonella: Recent developments.
  127. (2007). MegaPlex PCR: a strategy for multiplex amplification.
  128. (2001). Melting curve analysis of SNPs (McSNP): a gel-free and inexpensive approach for SNP genotyping.
  129. (2004). Microarray-Based Identification of Bacteria in Clinical Samples by Solid-Phase PCR
  130. (1997). Minisequencing: A Specific Tool for DNA Analysis and Diagnostics on Oligonucleotide Arrays. Genome Res.
  131. (2002). Minor groove binderconjugated DNA probes for quantitative DNA detection by hybridization-triggered fluorescence.
  132. (2004). Molecular diagnosis of haemoglobin disorders.
  133. (2005). Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies.
  134. (2004). Moving towards individualized medicine with pharmacogenomics.
  135. (1998). Multicolor molecular beacons for allele discrimination.
  136. (2007). Multigene amplification and massively parallel sequencing for cancer mutation discovery.
  137. (2001). Multiplex allele-specific target amplification based on PCR suppression.
  138. (2005). Multiplex amplification enabled by selective circularization of large sets of genomic DNA fragments.
  139. (2007). Multiplex amplification of all coding sequences within 10 cancer genes by Gene-Collector.
  140. (2006). Multiplex amplification of the mammoth mitochondrial genome and the evolution of Elephantidae.
  141. (1996). Multiplex genotype determination at a large number of gene loci.
  142. (2003). Multiplex Minisequencing Screen for Common Southeast Asian and Indian β-Thalassemia Mutations.
  143. (2003). Multiplex PCR design strategy used for the simultaneous amplification of 10 Y chromosome short tandem repeat (STR) loci.
  144. (1994). Multiplex PCR: advantages, development, and applications.
  145. (1997). Multiplex PCR: Critical Parameters and Step-by-Step Protocol.
  146. (2002). Multiplex polymerase chain reaction: A practical approach.
  147. (2002). Multiplex SNP genotyping in pooled DNA samples by a four-colour microarray system.
  148. (2006). Multiplexed DNA sequencing-by-synthesis.
  149. (2003). Multiplexed genotyping with sequence-tagged molecular inversion probes.
  150. (1992). multiplexing, and application of ARMS tests for common mutations in the CFTR gene.
  151. (2000). Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion.
  152. (1996). Mutations responsible for reduced susceptibility to 4-quinolones in clinical isolates of multiresistant Salmonella typhi in India.
  153. (2007). NCI-NHGRI Working Group on Replication in Association Studies et al. Replicating genotypephenotype associations.
  154. (2002). New developments in high-throughput resequencing and variation detection using high density microarrays.
  155. (2007). Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on
  156. (1996). Oligonucleotide ligation assay (OLA) for the diagnosis of familial hypercholesterolemia.
  157. (1994). Padlock probes: circularizing oligonucleotides for localized DNA detection.
  158. (2003). Parallel gene analysis with allele-specific padlock probes and tag microarrays.
  159. (2004). Parallel Genotyping of Over 10,000 SNPs Using a One-Primer Assay on a High-Density Oligonucleotide Array.
  160. (1999). Polymorphism identification and quantitative detection of genomic DNA by invasive cleavage of oligonucleotide probes.
  161. Probes for DASH genotyping Oligo Name Modification Oligo Sequence
  162. (1999). Prospects for whole-genome linkage disequilibrium mapping of common disease genes.
  163. (2000). Rapid {beta}-Globin Genotyping by Multiplexing Probe Melting Temperature and Color.
  164. (1989). Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction.
  165. (2007). Rapid carrier screening for β-thalassemia by single-step allele-specific PCR and detection.
  166. (2005). Rapid detection of deletional alpha-thalassemia by an oligonucleotide microarray.
  167. (2007). Rapid detection of gyrA and parC mutations in quinolone-resistant Salmonella enterica using Pyrosequencing® technology.
  168. (2004). Rapid detection of quinolone-resistant Salmonella by real time SNP genotyping.
  169. (2003). Rapid Detection of β-Globin Gene Mutations and Polymorphisms by Temporal Temperature Gradient Gel Electrophoresis.
  170. (2003). Rapid Screening of Multiple β-Globin Gene Mutations by Real-Time PCR on the LightCycler: Application to Carrier Screening and Prenatal Diagnosis of Thalassemia Syndromes.
  171. (1996). Real-Time DNA Sequencing Using Detection of Pyrophosphate Release.
  172. (1997). Real-time fluorescence genotyping of factor V Leiden during rapidcycle PCR.
  173. (2004). Real-time PCR for single-cell genotyping in sickle cell and thalassemia syndromes as a rapid, accurate, reliable, and widely applicable protocol for preimplantation genetic diagnosis.
  174. (2002). Reliability of DHPLC in mutational screening of beta-globin (HBB) alleles.
  175. (2002). Reliable Detection of β-Thalassemia and G6PD Mutations by a DNA Microarray.
  176. (1999). Resequencing and mutational analysis using oligonucleotide microarrays.
  177. (1994). Resonance Energy Transfer: Methods and Applications.
  178. (2001). Robust and Accurate Single Nucleotide Polymorphism Genotyping by Dynamic Allele-Specific Hybridization (DASH): Design Criteria and Assay Validation. Genome Res.
  179. (1998). Role of mutation in the gyrA and parC genes of nalidixic-acid-resistant salmonella serotypes isolated from animals in the United Kingdom.
  180. (2005). Scanning the betaglobin gene for mutations in large populations by denaturing capillary and gel electrophoresis.
  181. (2001). Science medicine and the future: Postgenomic technologies: hunting the genes for common disorders.
  182. (2003). Scoring insertion-deletion polymorphisms by dynamic allele-specific hybridization.
  183. (2003). Screening and genetic diagnosis of haemoglobin disorders.
  184. (2003). Screening Method for Salmonella enterica Serovar Typhi and Serovar Paratyphi A with Reduced Susceptibility to Fluoroquinolones by PCR-Restriction Fragment Length Polymorphism.
  185. (2000). Searching for genetic determinants in the new millennium.
  186. (2005). Segmental duplications and copy-number variation in the human genome.
  187. (2004). Selecting a Maximally Informative Set of Single-Nucleotide Polymorphisms for Association Analyses Using Linkage Disequilibrium.
  188. (2003). Selection of Genetic Markers for Association Analyses, Using Linkage Disequilibrium and Haplotypes.
  189. (2004). Selective DNA amplification from complex genomes using universal double-sided adapters.
  190. (2006). Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing.
  191. (2004). Sensitivity and Specificity of Single-Nucleotide Polymorphism Scanning by High-Resolution Melting Analysis.
  192. (1998). Signal amplification of padlock probes by rolling circle replication.
  193. (2004). Single nucleotide polymorphism genotyping by two colour melting curve analysis using the MGB Eclipse™ Probe System in challenging sequence environment.
  194. (2005). Single-strand conformation polymorphism analysis of candidate genes for reliable identification of alleles by capillary array electrophoresis.
  195. (2000). Single-tube multiplex-PCR screen for common deletional determinants of alpha -thalassemia.
  196. (2003). Skin pigmentation, biogeographical ancestry and admixture mapping.
  197. (2001). SNP Genotyping by Multiplexed Solid-Phase Amplification and Fluorescent Minisequencing. Genome Res.
  198. (2000). Solid phase DNA amplification: characterisation of primer attachment and amplification mechanisms.
  199. (2001). Solid-Phase Amplification for Detection of C282Y and H63D Hemochromatosis (HFE) Gene Mutations.
  200. (2002). Solid-phase PCR in microwells: effects of linker length and composition on tethering, hybridization, and extension.
  201. (2001). Solid-Phase PCR with Hybridization and Time-resolved Fluorometry for Detection of HLA-B27.
  202. (1997). Steric factors influencing hybridisation of nucleic acids to oligonucleotide arrays.
  203. (2004). Strategies for covalent attachment of DNA to beads.
  204. (1987). Temperature-gradient gel electrophoresis. Thermodynamic analysis of nucleic acids and proteins in purified form and in cellular extract.
  205. (2001). Temperature-Modulated Array High-Performance Liquid Chromatography.
  206. (2000). The common PPAR[gamma] Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.
  207. (2007). The Diploid Genome Sequence of an Individual Human.
  208. (1997). The elimination of primer-dimer accumulation in PCR.
  209. (2007). The ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.
  210. (1999). The essence of SNPs.
  211. (1996). The future of genetic studies of complex human diseases.
  212. (2005). The genome of the social amoeba Dictyostelium discoideum.
  213. (2004). The Human MitoChip: A High-Throughput Sequencing Microarray for Mitochondrial Mutation Detection.
  214. (2005). The Invader assay for SNP genotyping.
  215. (2006). The potential of electrophoretic mobility shift assays for clinical mutation detection.
  216. (2007). The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
  217. (2005). Toward genome-wide SNP genotyping. Nat Genet. 37 Supplement,
  218. (2006). Towards compendia of negative genetic association studies: an example for Alzheimer disease.
  219. (2003). Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations.
  220. (2007). Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
  221. (2001). Use of a LightCycler gyrA Mutation Assay for Rapid Identification of Mutations Conferring Decreased Susceptibility to Ciprofloxacin in Multiresistant Salmonella enterica Serotype Typhimurium DT104 Isolates.
  222. (2002). Use of a rapid mismatch PCR method to detect gyrA and parC mutations in ciprofloxacin-resistant clinical isolates of Escherichia coli.
  223. (2006). Use of HAPPY mapping for the higher order assembly of the Tetrahymena genome.
  224. (2000). Use of immobilized PCR primers to generate covalently immobilized DNAs for in vitro transcription/translation reactions.
  225. (1990). Use of uracil DNA glycosylase to control carryover contamination in polymerase chain reactions.
  226. (2003). Validation of a novel, fully integrated and flexible microarray benchtop facility for gene expression profiling.
  227. (2005). What makes a good genetic association study?
  228. (2006). Whole-genome genotyping with the single-base extension assay.
  229. (2001). Y-Chromosomal SNPs in Finno-Ugric-Speaking Populations Analyzed by Minisequencing on Microarrays. Genome Res.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.