Advances in Genomic Experiment Techniques

The experimental designs in the laboratory for the SNP analysis can be grouped into two main types of methods (Kwok, 2002). The first ones are those for the detection of the mutation and SNP. These include methods like the denaturing highperformance liquid (dHPLC) (Xiao and Oefner, 2001), single-strand conformation polymorphism (SSCP) (Orita et al., 1989), conformation-sensitive gel electrophoresis (CSGE) (Gonen et al., 1999; Oto et al., 1993), and chemical cleavage (Ellis et al., 1998) and lastly the direct DNA sequencing. This direct DNA is in fact the gold standard for mutation detection and single nucleotide polymorphism discovery, even though it is relatively laborious in comparison with other methods (Taillon-Miller et al., 1999).

Another type of the methods is for the genotyping of the SNPs detected. These include: Taqman assay (Holland et al., 1991), single-base extension approaches (Hacia, 1999), pyrosequencing (Ahmadian et al., 2000; Alderborn et al., 2000), ligation (Nilsson et al., 2001), Invader assay (Ryan et al., 1999), primer extension with mass spectrometry detection (Karas and Hillenkamp, 1988; Buetow et al., 2001), and molecular beacons etc. The molecular beacons (Tyagi et al., 1998; Marras et al., 1999) work with the fluorescent colors, which are generated in sealed amplification tubes, for typing the single nucleotide polymorphism. The molecular beacons are especially suited for the SNP analysis, because their ability for the recognitions of the targets is of much higher specificity than traditional oligonucleotide probes. Besides the above discussion of the laboratory works for the discovery and the genotyping of SNPs, we will also talk briefly about the computational efforts for the discovery of SNPs in the following section.