@article{Wang2010, abstract = {The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10 g-8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. © 2010 Macmillan Publishers Limited. All rights reserved.}, author = {Wang, Wei and Xue, Y. and Abecasis, Gonçalo R. and Altshuler, David L. and De la Vega, Francisco M. and 1000, Genomes Project Consortium and McEwen, Jean E. and Wang, Jun and Li, Jingxiang and Wang, Jian and McGuire, Amy L. and Li, Ruiqiang and Li, Taosha and Wang, Bo and Zhang, Xiuqing and Li, Guoqing and McVean, Ga A. and Wang, Shally Jun and Stone, Jennifer and Lee, Clarence C. and Zöllner, Sebastian and Bentley, I. David R. and Zheng, Huisong and Sahinalp, S. C. and Clark, Shauna and Mc Kernan, K. J. and Gr, Abecasis and McLellan, Mike D. and Wang, S. and Zheng, Hancheng and Fulton, Robert and Wu, Jiantao and Yu, Jin and Li, Yingrui and Chen, Wei and Huang, Weichun and Zheng, Xiaole and Auton, Adam and Lee, Wan-Ping and Xin, and Mcvean, Gil A. and Humphray, Sean and Mccarroll, Steven A. and Ye, Kenny and Li, Heng and Ld, Brooks and Schaffner, Stephen F. and Mckenna, Aaron and Xia, and Lee, W.-P. and Keane, Thomas M. and Abyzov, Alexej and Rm, Durbin and Stuetz, Adrian M. and Ra, Gibbs and Scheet, Paul and Sidore, Carlo and Zilversmit, Martine and Turcotte, Cynthia and Me, Hurles and Xing, Jinchuan and Snyder, Matthew and Ball, Edward Vincent and Xiao, Chunlin and Walker, Jerilyn A. and Tumian, Afidalina and Tsung, Eric F. and Song, Wanmin and Rotmistrovsky, Kirill E. and Sudmant, Peter H. and Indap, Amit and Weinstock, George and Wallis, John W. and Turner, Daniel and Urban, Alexander E. and Walter, Klaudia and Sanders, Robert D. and Kural, Deniz and Zalunin, Vadim and Tembe, Waibhav D. and Skelly, Tom and Winer, Roger and Wendl, Michael C. and Sabeti, Pardis C. and Timmermann, Bernd and Shumway, Martin F. and Sakarya, Onur and Ye, Kai and Wu, Honglong and Rosenstiel, Philip and Yu, Fuli and Sun, Yongming A. and Leong, Wen Fung and Smith, Richard E. and Yoon, Seungtai C. and Stalker, James and Tolzmann, Marius and Swerdlow, Harold P. and Wilson, Richard K. and Sinari, Shripad A. and Zhou, Yan and Schreiber, Stefan and Shlyakhter, Ilya A. and Schafer, Alan J. and Stenson, Peter Daniel and Sabo, Aniko and Wheeler, David and Soldatov, Aleksey V. and Ward, Alistair N. and Sudbrak, Ralf and Shefler, Erica and Sherry, Stephen T. and Tian, Geng and Sougnez, Carrie L. and Stewart, Chip and Mealmaker, Craig and Sebat, Jonathan and Tai, Shuaishuai and Stromberg, Michael P. and Desany, Brian and Shi, Xinghua and Yang, Huanming and Celone, Christopher and Minderman, Melissa and Ashworth, Dana and Caprio, Amanda and Affourtit, Jason and Burke, Adam and Buglione, Eli and Gibbs, Richard A. and Bachorski, Melissa and Nawrocki, Anne and Attiya, Said and Batzer, Mark A. and Mu, Xinmeng Jasmine and Tyler-Smith, Chris and Borodina, Tatiana A. and Ambrogio, Lauren and Mertes, Florian and Niazi, Faheem and Ichikawa, Jeffry K. and Reynolds, Andy and Costa, Gina L. and Banks, Eric and Egholm, Michael and Bentley, David R. and Metzker, Mike and Ball, Aaron D. and DePristo, Mark A. and Pareja, Kristen and Daly, Mark J. and Conners, David and Mills, Ryan E. and Chakravarti, Aravinda and Dahl, Andreas and Ga, McVean and Bloom, Toby and Palotie, Aarno and Nietfeld, Wilfiried and Jian, Min and Gu, Lisa and Koko-Gonzales, Paula and Przeworski, Molly and Kingsbury, Zoya and Durbin, Richard M. and Fennell, Tim J. and Radhakrishnan, Rajesh and Gabriel, Stacey B. and Murray, Lisa and Cibulskis, Kristian and Lehrach, Hans and McLaughlin, Stephen F. and Muzny, Donna and Lander, Eric S. and Peltonen, Leena and Bustamante, Carlos D. and Collins, Francis S. and Clark, Andrew G. and Reid, Jeff and Browning, Brian L. and Gormley, Niall and Liang, Huiqing and Boyko, Adam and Donnelly, Peter and Guccione, Lorri and Christoforides, Alexis and Ramenani, Ravi and Moffatt, Miriam F. and Deiros, David and Haussler, David and Awadalla, Philip and Toji, Lorraine H. and Beckstrom-Sternberg, Steve M. and Jaffe, David B. and Lathrop, Mark and Moutsianas, Loukas and Cunningham, Fiona and Craig, David W. and Stütz, Adrian M. and Mardis, Elaine R. and Davydov, Alexey N. and Carter, David M. and Khurana, Ekta and Flicek, Paul and Quail, Michael and Montgomery, Stephen B. and Burton, John and Degenhardt, Jeremiah and Katzman, Sol J. and Parkhomchuk, Dimitri V. and Nemesh, James C. and Riches, David and Hinrichs, Angie S. and Fu, Yutao and Dooling, David and Grubert, Fabian and Bauer, Markus and Marquardt, Peter and Quinlan, Aaron R. and Gutenkunst, Ryan N. and Kuhn, Robert M. and Lam, Hugo Y. K. and Ayub, Qasim and Garimella, Kiran V. and Marth, Gabor T. and Parts, Leopold and Gravel, Simon and Kern, Andrew and Albers, Cornelis A. and Ding, Jun and Bjornson, Robert and Makarov, Vladimir and Knight, James and Cookson, William O. and Leinonen, Rasko and Kao, Kalvin and Kurdoglu, Ahmet A. and Lacroute, Phil and Haraksingh, Rajini and Wilkinson, Jane and Casals, Ferran and Gerstein, Mark B. and Hernandez, Ryan D. and Keinan, Alon and Barrett, Jeffrey C. and Knoppers, Bartha M. and Myers, Simon and Fulton, Lucinda and Habegger, Lukas and Blackwell, Tom and Keenen, Stephen and Hurles, Matt E. and Luo, Ruibang and Kaganovich, Mark and Balasubramaniam, Senduran and Grossman, Sharon Rachel and Anderson, Paul and Mort, Matthew Edwin and Knowlton, Jennifer and Alkan, Can and Kebbel, Andrew and Philippakis, Anthony A. and Kahn, Scott and Konkel, Miriam K. and Kelley, Joanna L. and Korbel, Jan O. and Aksay, Gozde and De Witte, Anniek and Iqbal, Zamin and James, Terena and Howie, Bryan and Hanna, Matt and Eichler, Evan E. and Eberle, Michael and Handsaker, Robert E. and Phillips, Andrew David and Coffey, Alison and Morgulis, Aleksandr O. and Labrecque, Matthew and Lindsay, Sarah and Garrison, Erik P. and Jorde, Lynn and Albrecht, Marcus W. and Kovar, Christie and Churcher, Carol and Kang, Hyun Min and Chinwalla, Asif and Dinh, Huyen and Dermitzakis, Emmanouil T. and Guo, Xiaosen and Rotimi, Charles N. and Peckham, Heather E. and Lunter, Gerton and Keebler, John and Coafra, Cristian and Danecek, Petr and Hartl, Chris and Fang, Xiaodong and Jostins, Luke and Idaghdour, Youssef and Conrad, Donald F. and Kulesha, Eugene and Jin, Hanjun and Kidd, Jeffrey M. and Cox, Anthony and McDade, Louise and Long, Quan and Amstislavskiy, Vyacheslav S. and Nazareth, Lynne and Nickerson, Debbie A. and Hormozdiari, Fereydoun and Koboldt, Daniel C. and Hu, Min and Hajirasouliha, Iman and Peterson, Jane L. and Poplin, Ryan E. and Cooper, David Neil and Phan, Lon D. and Paschall, Justin E. and Rivas, Manuel A. and Price, Alkes and Marchini, Jonathan L. and Clarke, Laura and Green, Eric D. and Jee, Justin and Scott, Carol and MacArthur, Daniel G. and Duncanson, Audrey and Clemm, Nicholas C. and Hyland, Fiona C. L. and Challis, Danny and Juenger, Christopher R. and Bainbridge, Matthew and Abdallah, Assya and Guyer, Mark S. and Agarwala, Richa and Giles, Shane and Felsenfeld, Adam L. and Herwig, Ralf and Brooks, Lisa D. and Su, Yeyang and Du, Jiang and Kernytsky, Andrew M. and Manning, Jonathan M. and Korn, Joshua M. and Gharani, Neda and Cenk Sahinalp, S. and Khouri, Hodam and Maguire, Jared R. and Ossorio, Pilar N. and Kent, Alastair and Kaye, Jane S. and Cord Melton, S. and Le, Si Quang and Keira Cheetham, R. and McLaren, William M. and Cox, Tony and Pearson, John V. and McKernan, Kevin J. and Lee, Clarence Charles and Humphray, I. Sean and Li, Yun and Khouri, Hoda M. and Zoellner, Sebastian and Zheng-Bradley, Xiangqun and Zhan, Xiaowei and Ma, Xin and Chen, Yuan and Stone, Eric A. and Liang, Liming and Abecasis, Gonçalo R. and Snyder, Michael and Herrero, Javier and Zhang, Qunyuan and Cheetham, R. Keira and Zhang, Zhengdong and Chen, Ken and Ding, Li and Fung Leong, Wen and Zhang, Yujun and Huang, Ni and Melton, S. C. and Balasubramanian, Suganthi and Leng, Jing and Min Kang, Hyun and Lee, Sandy and CenkSahinalp, S. and Quang Le, Si and Coffey, Allison and Kebbler, J. and Jasmine Mu, Xinmeng and Abecasis, Goncalo R. and Group, 1000 Genomes Consortium and Consortium, 1000 Genomes Project and Cartwright, R. A.}, doi = {10.1038/nature09991}, journal = {Nature}, month = {oct}, pages = {544-544}, title = {A map of human genome variation from population-scale sequencing}, url = {http://www.nature.com/nature/journal/v467/n7319/pdf/nature09534.pdf}, volume = {473}, year = {2010} }