Large-Scale Identification, Mapping, and Genotyping of Single-Nucleotide Polymorphisms in the Human Genome

作者：David G. Wang, Jian‐Bing Fan, Chia-Jen Siao, Anthony J. Berno, Peter R. Young, Ron Sapolsky, Ghassan Ghandour, Nancy J. Perkins, Ellen Winchester, Jessica B. Spencer, Leonid Kruglyak, Lincoln Stein, Linda Hsie, Thodoros Topaloglou, Earl A. Hubbell, Elizabeth A. Robinson, Michael Mittmann, Macdonald S. Morris, Naiping Shen, Dan Kilburn, John David Rioux, Chad Nusbaum, Steve Rozen, Thomas Jay Hudson, Robert J. Lipshutz, Mark S. Chee, Eric S. Lander · 发表于：Science · 年份：1998 · DOI：10.1126/science.280.5366.1077 · 被引用次数：2185 · 研究领域：Molecular Biology Techniques and Applications、Genomics and Phylogenetic Studies、RNA and protein synthesis mechanisms

Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.