Single-Nucleotide Polymorphisms: Technology and Applications

The genomics revolution is transforming epidemiology, medicine, and drug discovery (1 –7 ) and there is an ongoing refocusing of effort away from family-based linkage studies toward population-based genetic association studies for complex phenotypes (3 ,8 –11 ). The generation of new genomic knowledge and its integration into epidemiological and clinical research projects in industry and academia are exponentially increasing trends. The genetic basis of disease susceptibility, disease progression and severity, and response to therapy for many complex conditions has been increasingly emphasized in medical research, with the ultimate goal of improving preventive strategies, diagnostic tools, and therapies (4 ,5 ,12 ,13 ). Enormous effort in both academia and industry has been expended in genetic studies of complex human diseases over the last decade. Concomitant technical developments in molecular genetics and in the use of polymorphism directly derived from DNA sequence have occurred, and extensive catalogs of DNA sequence variants across the human genome have been constructed (14 –16 ) (see the Appendix, p. 247). The completion of the human genome project and the application of highthroughput technologies for polymorphism detection to the investigation of complex disease genetics has created unprecedented opportunities for understanding the pathogenic basis of common human diseases (1 ,16 ).