Tiling arrays are a subtype of microarray chips. Like traditional microarrays, they function by hybridizing labeled DNA or RNA target molecules to probes fixed onto a solid surface.
Tiling arrays differ from traditional microarrays in the nature of the probes. Instead of probing for sequences of known or predicted genes that may be dispersed throughout the genome, tiling arrays probe intensively for sequences which are known to exist in a contiguous region. This is useful for characterizing regions that are sequenced, but whose local functions are largely unknown. Tiling arrays aid in transcriptome mapping as well as in discovering sites of DNA/protein interaction (ChIP-chip, DamID), of DNA methylation (MeDIP-chip) and of sensitivity to DNase (DNase Chip) and array CGH. In addition to detecting previously unidentified genes and regulatory sequences, improved quantification of transcription products is possible. Specific probes are present in millions of copies (as opposed to only several in traditional arrays) within an array unit called a feature, with anywhere from 10,000 to more than 6,000,000 different features per array. Variable mapping resolutions are obtainable by adjusting the amount of sequence overlap between probes, or the amount of known base pairs between probe sequences, as well as probe length. For smaller genomes such as Arabidopsis, whole genomes can be examined. Tiling arrays are a useful tool in genome-wide association studies.
Synthesis and manufacturers
The two main ways of synthesizing tiling arrays are photolithographic manufacturing and mechanical spotting or printing.
The first method involves in situ synthesis where probes, approximately 25bp, are built on the surface of the chip. These arrays can hold up to 6 million discrete features, each of which contains millions of copies of one probe.
The other way of synthesizing tiling array chips is via mechanically printing probes onto the chip. This is done by using automated machines with pins that place the previously synthesized probes onto the surface. Due to the size restriction of the pins, these chips can hold up to nearly 400,000 features. Three manufacturers of tiling arrays are Affymetrix, NimbleGen and Agilent. Their products vary in probe length and spacing. ArrayExplorer.com is a free web-server to compare tiling arrays.
Applications and types
ChIP-chip
ChIP-chip is one of the most popular usages of tiling arrays. Chromatin immunoprecipitation allows binding sites of proteins to be identified. A genome-wide variation of this is known as ChIP-on-chip. Proteins that bind to chromatin are cross-linked in vivo, usually via fixation with formaldehyde. The chromatin is then fragmented and exposed to antibodies specific to the protein of interest. These complexes are then precipitated. The DNA is then isolated and purified. With traditional DNA microarrays, the immunoprecipitated DNA is hybridized to the chip, which contains probes that are designed to cover representative genome regions. Overlapping probes or probes in very close proximity can be used. This gives an unbiased analysis with high resolution. Besides these advantages, tiling arrays show high reproducibility and with overlapping probes spanning large segments of the genome, tiling arrays can interrogate protein binding sites, which harbor repeats. ChIP-chip experiments have been able to identify binding sites of transcription factors across the genome in yeast, drosophila and a few mammalian species.