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Jan 1, 2009 (Vol. 29, No. 1)

Utilization of DNA Microarrays Increasing

Persistent Doubts about Reproducibility and Compatability of Data Are Being Overcome

  • One of the hottest research tools these days within the academic, biotech, and pharma communities is DNA microarrays. The concept morphed from the now-classical Southern blotting procedure into the present highly automated systems for screening hundreds of thousands of gene sequences. Because of their huge scanning capability, DNA microarrays can drive R&D programs that would have been impossible before the advent of this technology.

    Southern blotting, now over three decades old, is based on the transfer to nitrocellulose of DNA molecules separated on gels, and their subsequent identification with DNA probes. This was one of the early applications of the highly specific pairing properties of single strands of DNA for their homologous partners. Using radioactively labeled probes, a single gene could be picked out from an entire genome.

    The principle was expanded and automated in the development of DNA microarrays, which consist of an arrayed series of thousands of microscopic spots of DNA oligonucleotides, each containing tiny amounts of a specific DNA sequence.

    The arrays are printed on a platform, usually a glass slide. The probe will hybridize with samples of homologous nucleic acids, as detected by fluorophore-labeled targets whose signal is proportional to the relative abundance of nucleic acid sequences in the target, making it possible to examine the relative activity of thousands of genes at any given time.

  • Applications

    Click Image To Enlarge +
    Roche NimbleGen’s 12 plex array offers 12 samples per array and 135 K features on each of 12 subarrays.

    Microarray technology is being applied to the investigation of heart disease, mental illness, infectious diseases, and cancer. It is now possible to classify cancers based on the patterns of gene activity in the tumor cells, suggesting that it will be feasible to design treatment strategies focused on specific malignancies.

    According to Justin O’Kelly, a spokesperson for Affymetrix, among his company’s most notable genotyping products are the Genome-Wide Human SNP Array 6.0 and the new Genotyping Console 3.0.1 software (GTC 3.0.1).

    The SNP Array 6.0 is a single microarray that measures more than 1.8 million markers for genetic variation, according to the company. It consists of 906,600 SNPs and 946,000 copy-number probes. The array enables researchers to perform whole-genome association studies by genotyping more markers from more individuals at a lower cost per sample. These studies increase the probability of discovering genes associated with adverse drug response or complex diseases such as Alzheimer’s, diabetes, heart disease, and Parkinson’s disease.

    Integrating SNP genotyping, copy-number polymorphism (CNP) genotyping, and rare copy number variation identification in one data analysis application, the SNP 6.0 Array and the GTC 3.0.1 enable researchers to bridge CNP genotyping and classical SNP genotyping analysis in one genome-wide association study and/or high-resolution cytogenetic analysis, the company reports.

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