ChIP Chips

Epigenetics, which is the study of different factors that influence gene regulation, has become one of the hottest applications in genomic research. Basically, researchers in epigenetics are trying to understand the mechanisms that govern cell activity and differentiate cell phenotypes. For example, eye and skin cells behave differently despite having the same genetic makeup. This field goes beyond functional genomics and gene expression by providing insights to a complex control system that turns genes on or off.

A significant focus of epigenetics is chromatin, a DNA and protein structure that plays a role in controlling expression. Researchers use chromatin immunoprecipitation (ChIP) assays to identify the location of DNA-binding sites.

While traditional methods use specifically designed PCR primers for identification, ChIP assays are also performed on microarrays (ChIP chips), particularly for whole genome assays. Researchers are using ChIP chips to create genome-wide maps of events that affect gene regulation, such as methylation and acetylation. By understanding patterns in these binding sites, researchers hope to uncover potential biomarkers for genetic disorders and cancer.

The leading microarray companies introduced new ChIP microarrays in 2006. Early in the year, Affymetrix launched a nine-tiling array for five different organisms. These high-density tiling array sets interrogate all of the nonrepetitive portions of the various genomes. NimbleGen later announced a limited-access program for its NimbleChip HD2, which offers more than 2.1 million probes for ChIP applications for 10 different organisms. According to NimbleGen, the probe density of the HD2 reduces a whole-genome scan from 38 arrays to about seven. Agilent Technologies launched its next-generation ChIP microarrays that offer a sixfold increase in density over its previous chips. The chips are available in two formats: a microarray with 244,000 features and a four-tile microarray with more than 44,000 features per tile.

While ChIP chips have proven to be a powerful technology for genome-wide localization analysis, there are some potential drawbacks to their use, including a bias for PCR amplification, low sensitivity and low resolution. To address these shortcomings, Illumina offers a unique ChIP-Seq method, which uses a combination of ChIP assays and its Genome Analyzer DNA sequencer. The ChIP-Seq method scans millions of binding sites within one channel of a flow cell at a cost Illumina claims to be 10–30 times lower than standard ChIP-chip approaches.

The total market for ChIP chips accounted for only a small percentage of the $1.0 billion microarray market in 2005. However, it has certainly become one the leading techniques in genomic research, with an estimated growth rate higher than 40% over the next few years.

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