Basic molecular techniques for the detection of single nucleotide polymorphisms: genome-wide applications in search...

The necessity of genotyping high number of variations in extended sample sets has become apparent in the era of large genomic studies of common complex disorders, in cancer and in pharmacogenomics. The single nucleotide polymorphisms' (SNPs) apparent advantages over other genetic markers such as high frequency, relative stability, and statistically random distribution across the genome have made them a method of choice for most of these genome-wide oriented applications. The requirement for simultaneous genotyping of high number of SNPs, keeping at the same time reasonable price and reliable accuracy, triggered the rise of the genotyping throughput, and led to the development of the array-based technologies. The present chapter briefly reviews the methodological and historical aspect of the basic SNP detecting techniques that lie in the basis of the modern high-throughput technologies, providing at the same time detailed guide on the application of one of the most advanced SNP microarray platform on the market: the genome-wide SNP Array 6.0 recently developed by Affymetrix, which we have used to study families with Catney complex and Micronodular adrenocortical hyperplasia. In addition, we discuss practical clues and tips aiming at extending applications and improving performance.