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Microarray technology: beyond transcript profiling and genotype analysis

Key Points

  • Microarray technology encompasses a few relatively well-established methods and numerous applications that are in various stages of development.

  • Apart from their use as a tool for diagnostic testing in a broad sense, microarrays have also become a means for molecule production.

  • For real diagnostics, data interpretation is frequently the main obstacle.

  • Because of biological complexity, molecular patterns rather than individual markers will be used in the future.

  • For research purposes, microarrays will be transformed from rigid platforms, each made for a specific purpose, to flexible tools. Technical developments and new design formats will enable this transformation.

  • In the long term, technology that originates from microarray technology will allow 'experimental' systems biology.

Abstract

Understanding complex functional mechanisms requires the global and parallel analysis of different cellular processes. DNA microarrays have become synonymous with this kind of study and, in many cases, are the obvious platform to achieve this aim. They have already made important contributions, most notably to gene-expression studies, although the true potential of this technology is far greater. Whereas some assays, such as transcript profiling and genotyping, are becoming routine, others are still in the early phases of development, and new areas of application, such as genome-wide epigenetic analysis and on-chip synthesis, continue to emerge.

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Figure 1: Scheme for identifying unknown exons.
Figure 2: On-chip chromatin immunoprecipitation (ChIP-on-chip).
Figure 3: Comparative genomic hybridization (CGH).
Figure 4: In situ synthesis of RNAi libraries.
Figure 5: A universal chip that is based on L-DNA.

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Acknowledgements

The author thanks colleagues for sharing unpublished results and many interesting discussions. Relevant work in his laboratory was funded by grants from the Federal German Ministry of Education and Research (BMBF), the Deutsche Forschungsgemeinschaft and the European Commission.

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FURTHER INFORMATION

Bioconductor

Gene Ontology Consortium

International HapMap Project

The Microarray Gene Expression Data (MGED) Society

MolTools — advanced molecular tools for array-based analyses of genomes

Glossary

Secondary-ion mass spectrometry

A technique in which a focused ion beam is directed to a solid surface, removing material in the form of neutral and ionized atoms and molecules. The secondary ions are then accelerated into a mass spectrometer and separated according to their mass-to-charge ratio.

Tiling path

The coverage of a given genomic region by a set of overlapping DNA fragments.

Serial analysis of gene expression

A method for analysing transcription patterns. A short cDNA tag sequence of 10 to 14 bp is isolated for each transcript. They are linked at random to form long concatemeric molecules that can be sequenced to determine the frequency of each tag sequence, and therefore the respective RNA, in the entire population.

Solid-phase synthesis

A chemical synthesis reaction during which the synthesized molecules are continuously attached to a solid support medium.

Phosphoramidite chemistry

The chemistry of choice for oligonucleotide synthesis; the stable tri-coordinated phosphorous function of one nucleoside phosphoramidite is activated by a weak acid and reacts with the hydroxyl moiety of another nucleoside.

RNAi

RNA-mediated, sequence-specific transcriptional silencing of gene expression.

Padlock probes

Linear DNA molecules of 70–100 nucleotides that become circularized by DNA ligation in the presence of a target sequence that is complementary to both terminal sequences of the probe molecule.

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Hoheisel, J. Microarray technology: beyond transcript profiling and genotype analysis. Nat Rev Genet 7, 200–210 (2006). https://doi.org/10.1038/nrg1809

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