Methods for genotyping single nucleotide polymorphisms

One of the fruits of the Human Genome Project is the discovery of millions of DNA sequence variants in the human genome. The majority of these variant s are single nucleotide polymorphisms (SNPs). A dense set of SNP markers op ens up the possibility of studying the genetic basis of complex diseases by population approaches. In all study designs, a large number of individuals must be genotyped with a large number of markers. In this review, the curr ent status of SNP genotyping is discussed in terms of the mechanisms of all elic discrimination, the reaction formats, and the detection modalities. A number of genotyping methods currently in use are described to illustrate t he approaches being taken. Although no single genotyping method is ideally suited for all applications, a number of good genotyping methods are availa ble to meet the needs of many study designs. The challenges for SNP genotyp ing in the near future include increasing the speed of assay development, r educing the cost of the assays, and performing multiple assays in parallel. Judging from the accelerated pace of new method development, it is hopeful that an ideal SNP genotyping method will be developed soon.