which variants might be causal, including more precise information on where to search for causal variants Going a major step beyond the HapMap, the 1000 Genomes Project will map not only the single-letter differences in peoples DNA, called single nucleotide polymorphism (SNPs), but also will produce a high-resolution map of larger differences in genome structure called structural variants. Structural variants are rearrangements, deletions or duplications of segments of the human genome. The importance of these variants has become increasingly clear with surveys completed in the past 18 months that show these differences in genome structure may play a role in susceptibility to certain conditions such as mental retardation and autism In addition to accelerating the search for genetic variants involved in susceptibility to common diseases, the map produced by the 1000 Genomes Project will provide a deeper understanding of human genetic variation and open the door to many other new findings of significance to both medicine and basic human biology The sequencing work will be carried out at the Sanger Institute, BGI Shenzhen and MIT and Harvard; the Washington University Genome Sequencing Center at the pn NHGRI'S Large-Scale Sequencing Network, which includes the Broad Institute Washington University School of Medicine in St Louis, and the Human Genome Sequencing Center at the Baylor College of Medicine in Houston. The consortium may add other participants over time The project depends on large-scale implementation of several new sequencing platforms Using standard DNA sequencing technologies, the effort would likely cost more than $500 million. However, leaders of the 1000 Genomes Project expect the costs to be far lower- in the range of s30 million to $50 million-because of the project's pioneering efforts to use new sequencing technologies in the most efficient and cost-effective manner In the first phase of the 1000 Genomes Project, lasting about a year, researchers will conduct three pilots the results of the pilots will be used to decide how to most efficiently and cost effectively produce the projects detailed map of human genetic variation The first pilot will involve sequencing the genomes of two nuclear families(both parents and an adult child) at deep coverage that averages 20 passes of each genome This will provide a comprehensive dataset from six people that will help the project figure out how to identify variants using the new sequencing platforms, and serve as a basis for comparison for other parts of the effort that averages two passes of each genome This will test the ability to use loy verage The second pilot will involve sequencing the genomes of 180 people at low co coverage data from new sequencing platforms to identify sequence variants and to put them in their genomic context The third pilot will involve sequencing the coding regions, called exons, of about 1,000 genes in about 1,000 people. This is aimed at exploring how best to obtain an3 which variants might be causal, including more precise information on where to search for causal variants. Going a major step beyond the HapMap, the 1000 Genomes Project will map not only the single-letter differences in people’s DNA, called single nucleotide polymorphisms (SNPs), but also will produce a high-resolution map of larger differences in genome structure called structural variants. Structural variants are rearrangements, deletions or duplications of segments of the human genome. The importance of these variants has become increasingly clear with surveys completed in the past 18 months that show these differences in genome structure may play a role in susceptibility to certain conditions, such as mental retardation and autism. In addition to accelerating the search for genetic variants involved in susceptibility to common diseases, the map produced by the 1000 Genomes Project will provide a deeper understanding of human genetic variation and open the door to many other new findings of significance to both medicine and basic human biology. The sequencing work will be carried out at the Sanger Institute, BGI Shenzhen and NHGRI’s Large-Scale Sequencing Network, which includes the Broad Institute of MIT and Harvard; the Washington University Genome Sequencing Center at the Washington University School of Medicine in St. Louis; and the Human Genome Sequencing Center at the Baylor College of Medicine in Houston. The consortium may add other participants over time. The project depends on large-scale implementation of several new sequencing platforms. Using standard DNA sequencing technologies, the effort would likely cost more than $500 million. However, leaders of the 1000 Genomes Project expect the costs to be far lower – in the range of $30 million to $50 million – because of the project’s pioneering efforts to use new sequencing technologies in the most efficient and cost-effective manner. In the first phase of the 1000 Genomes Project, lasting about a year, researchers will conduct three pilots. The results of the pilots will be used to decide how to most efficiently and cost effectively produce the project’s detailed map of human genetic variation. The first pilot will involve sequencing the genomes of two nuclear families (both parents and an adult child) at deep coverage that averages 20 passes of each genome. This will provide a comprehensive dataset from six people that will help the project figure out how to identify variants using the new sequencing platforms, and serve as a basis for comparison for other parts of the effort. The second pilot will involve sequencing the genomes of 180 people at low coverage that averages two passes of each genome. This will test the ability to use low￾coverage data from new sequencing platforms to identify sequence variants and to put them in their genomic context. The third pilot will involve sequencing the coding regions, called exons, of about 1,000 genes in about 1,000 people. This is aimed at exploring how best to obtain an