Methods, strategies and facts for improving the analysis of genetic variations using DNA arrays

Cancer is a disease resulting from the breakdown of several checkpoints and tumor-suppressing mechanisms. In cancer research, the development of new technologies, which have produced genomic tools indispensable for understanding how gene products are regulated in normal and diseased conditions on a global genome scale; one of these technologies is the DNA arrays. Although the most common use of DNA arrays is gene expression profiling and mutation detection, scientists have successfully used them for multiple applications, including genotyping, re-sequencing, DNA copy number analysis and DNA-protein interactions mainly. This section then will be dedicated to the use of a public sequence database that can be accessed, and the design of DNA oligonucleotide probes for oligoarrays derived from sequences of special interest. Single probe and stacking hybridization are explored as possible microarray designs. Then the use of thermodynamic models and in silico hybridization are explored in order to access the sensitivity and specificity of the oligoarray and how its design can be improved. However, many commercial and public applications do not consider that the hybridization between target DNA's and microarray probes is a chemical reaction which is influenced by several thermodynamic parameters. One of the most important of such parameters is the thermal stability of the nucleic acid duplexes, which are formed as a result of the hybridization. According to the reaction conditions, these duplexes can be perfectly or imperfectly paired, which is of critical importance when a diagnostic kit is developed in order to assess its sensitivity and specificity. In silico hybridization can be used to avoid undesired hybridization events (such as multiple target-probe interactions and stable mismatched hybrids). Also, the strategy can facilitate (through use of different length probes) selection of a probe set that has a narrow duplex stability allowing maximal specificity under a single hybridization condition.