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.
| Original language | English |
|---|---|
| Pages (from-to) | 1061-1073 |
| Number of pages | 13 |
| Journal | Nature |
| Volume | 467 |
| Issue number | 7319 |
| DOIs | |
| Publication status | Published - 28 Oct 2010 |
| Externally published | Yes |
Fingerprint
Dive into the research topics of 'A map of human genome variation from population-scale sequencing'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Nature, Vol. 467, No. 7319, 28.10.2010, p. 1061-1073.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - A map of human genome variation from population-scale sequencing
AU - Altshuler, David L.
AU - Durbin, Richard M.
AU - Abecasis, Gonçalo R.
AU - Bentley, David R.
AU - Chakravarti, Aravinda
AU - Clark, Andrew G.
AU - Collins, Francis S.
AU - De La Vega, Francisco M.
AU - Donnelly, Peter
AU - Egholm, Michael
AU - Flicek, Paul
AU - Gabriel, Stacey B.
AU - Gibbs, Richard A.
AU - Knoppers, Bartha M.
AU - Lander, Eric S.
AU - Lehrach, Hans
AU - Mardis, Elaine R.
AU - McVean, Gil A.
AU - Nickerson, Debbie A.
AU - Peltonen, Leena
AU - Schafer, Alan J.
AU - Sherry, Stephen T.
AU - Wang, Jun
AU - Wilson, Richard K.
AU - Deiros, David
AU - Metzker, Mike
AU - Muzny, Donna
AU - Reid, Jeff
AU - Wheeler, David
AU - Wang, Shenzhen Jun
AU - Li, Jingxiang
AU - Jian, Min
AU - Li, Guoqing
AU - Li, Ruiqiang
AU - Liang, Huiqing
AU - Tian, Geng
AU - Wang, Bo
AU - Wang, Jian
AU - Wang, Wei
AU - Yang, Huanming
AU - Zhang, Xiuqing
AU - Zheng, Huisong
AU - Ambrogio, Lauren
AU - Bloom, Toby
AU - Cibulskis, Kristian
AU - Fennell, Tim J.
AU - Jaffe, David B.
AU - Shefler, Erica
AU - Sougnez, Carrie L.
AU - Bentley, Illumina David R.
AU - Gormley, Niall
AU - Humphray, Sean
AU - Kingsbury, Zoya
AU - Koko-Gonzales, Paula
AU - Stone, Jennifer
AU - Mc Kernan, Kevin J.
AU - Costa, Gina L.
AU - Ichikawa, Jeffry K.
AU - Lee, Clarence C.
AU - Sudbrak, Ralf
AU - Borodina, Tatiana A.
AU - Dahl, Andreas
AU - Davydov, Alexey N.
AU - Marquardt, Peter
AU - Mertes, Florian
AU - Nietfeld, Wilfiried
AU - Rosenstiel, Philip
AU - Schreiber, Stefan
AU - Soldatov, Aleksey V.
AU - Timmermann, Bernd
AU - Tolzmann, Marius
AU - Affourtit, Jason
AU - Ashworth, Dana
AU - Attiya, Said
AU - Bachorski, Melissa
AU - Buglione, Eli
AU - Burke, Adam
AU - Caprio, Amanda
AU - Celone, Christopher
AU - Clark, Shauna
AU - Conners, David
AU - Desany, Brian
AU - Gu, Lisa
AU - Guccione, Lorri
AU - Kao, Kalvin
AU - Kebbel, Andrew
AU - Knowlton, Jennifer
AU - Labrecque, Matthew
AU - McDade, Louise
AU - Mealmaker, Craig
AU - Minderman, Melissa
AU - Nawrocki, Anne
AU - Niazi, Faheem
AU - Pareja, Kristen
AU - Ramenani, Ravi
AU - Riches, David
AU - Song, Wanmin
AU - Turcotte, Cynthia
AU - Wang, Shally
AU - Dooling, David
AU - Fulton, Lucinda
AU - Fulton, Robert
AU - Weinstock, George
AU - Burton, John
AU - Carter, David M.
AU - Churcher, Carol
AU - Coffey, Alison
AU - Cox, Anthony
AU - Palotie, Aarno
AU - Quail, Michael
AU - Skelly, Tom
AU - Stalker, James
AU - Swerdlow, Harold P.
AU - Turner, Daniel
AU - De Witte, Anniek
AU - Giles, Shane
AU - Bainbridge, Matthew
AU - Challis, Danny
AU - Sabo, Aniko
AU - Yu, Fuli
AU - Yu, Jin
AU - Fang, Xiaodong
AU - Guo, Xiaosen
AU - Li, Yingrui
AU - Luo, Ruibang
AU - Tai, Shuaishuai
AU - Wu, Honglong
AU - Zheng, Hancheng
AU - Zheng, Xiaole
AU - Zhou, Yan
AU - Marth, Gabor T.
AU - Garrison, Erik P.
AU - Huang, Weichun
AU - Indap, Amit
AU - Kural, Deniz
AU - Lee, Wan Ping
AU - Leong, Wen Fung
AU - Quinlan, Aaron R.
AU - Stewart, Chip
AU - Stromberg, Michael P.
AU - Ward, Alistair N.
AU - Wu, Jiantao
AU - Lee, Charles
AU - Mills, Ryan E.
AU - Shi, Xinghua
AU - Daly, Mark J.
AU - DePristo, Mark A.
AU - Ball, Aaron D.
AU - Banks, Eric
AU - Browning, Brian L.
AU - Garimella, Kiran V.
AU - Grossman, Sharon R.
AU - Handsaker, Robert E.
AU - Hanna, Matt
AU - Hartl, Chris
AU - Kernytsky, Andrew M.
AU - Korn, Joshua M.
AU - Li, Heng
AU - Maguire, Jared R.
AU - McKenna, Aaron
AU - Nemesh, James C.
AU - Philippakis, Anthony A.
AU - Poplin, Ryan E.
AU - Price, Alkes
AU - Rivas, Manuel A.
AU - Sabeti, Pardis C.
AU - Schaffner, Stephen F.
AU - Shlyakhter, Ilya A.
AU - Cooper, David N.
AU - Ball, Edward V.
AU - Mort, Matthew
AU - Phillips, Andrew D.
AU - Stenson, Peter D.
AU - Sebat, Jonathan
AU - Makarov, Vladimir
AU - Ye, Kenny
AU - Yoon, Seungtai C.
AU - Bustamante, Carlos D.
AU - Boyko, Adam
AU - Degenhardt, Jeremiah
AU - Gravel, Simon
AU - Gutenkunst, Ryan N.
AU - Kaganovich, Mark
AU - Keinan, Alon
AU - Lacroute, Phil
AU - Ma, Xin
AU - Reynolds, Andy
AU - Clarke, Laura
AU - Cunningham, Fiona
AU - Herrero, Javier
AU - Keenen, Stephen
AU - Kulesha, Eugene
AU - Leinonen, Rasko
AU - McLaren, William M.
AU - Radhakrishnan, Rajesh
AU - Smith, Richard E.
AU - Zalunin, Vadim
AU - Korbel, Jan O.
AU - Stütz, Adrian M.
AU - Humphray, Illumina Sean
AU - Bauer, Markus
AU - Cheetham, R. Keira
AU - Cox, Tony
AU - Eberle, Michael
AU - James, Terena
AU - Kahn, Scott
AU - Murray, Lisa
AU - Ye, Kai
AU - Fu, Yutao
AU - Hyland, Fiona C.L.
AU - Manning, Jonathan M.
AU - Stephen, F. McLaughlin
AU - Peckham, Heather E.
AU - Sakarya, Onur
AU - Sun, Yongming A.
AU - Tsung, Eric F.
AU - Mark, A. Batzer
AU - Konkel, Miriam K.
AU - Walker, Jerilyn A.
AU - Albrecht, Marcus W.
AU - Amstislavskiy, Vyacheslav S.
AU - Herwig, Ralf
AU - Parkhomchuk, Dimitri V.
AU - Agarwala, Richa
AU - Khouri, Hoda M.
AU - Morgulis, Aleksandr O.
AU - Paschall, Justin E.
AU - Phan, Lon D.
AU - Rotmistrovsky, Kirill E.
AU - Sanders, Robert D.
AU - Shumway, Martin F.
AU - Xiao, Chunlin
AU - Gil, A. McVean
AU - Auton, Adam
AU - Iqbal, Zamin
AU - Lunter, Gerton
AU - Marchini, Jonathan L.
AU - Moutsianas, Loukas
AU - Myers, Simon
AU - Tumian, Afidalina
AU - Knight, James
AU - Winer, Roger
AU - Craig, David W.
AU - Beckstrom-Sternberg, Steve M.
AU - Christoforides, Alexis
AU - Kurdoglu, Ahmet A.
AU - Pearson, John V.
AU - Sinari, Shripad A.
AU - Tembe, Waibhav D.
AU - Haussler, David
AU - Hinrichs, Angie S.
AU - Katzman, Sol J.
AU - Kern, Andrew
AU - Kuhn, Robert M.
AU - Przeworski, Molly
AU - Hernandez, Ryan D.
AU - Howie, Bryan
AU - Kelley, Joanna L.
AU - Melton, S. Cord
AU - Li, Yun
AU - Anderson, Paul
AU - Blackwell, Tom
AU - Chen, Wei
AU - Cookson, William O.
AU - Ding, Jun
AU - Kang, Hyun Min
AU - Lathrop, Mark
AU - Liang, Liming
AU - Moffatt, Miriam F.
AU - Scheet, Paul
AU - Sidore, Carlo
AU - Snyder, Matthew
AU - Zhan, Xiaowei
AU - Zöllner, Sebastian
AU - Awadalla, Philip
AU - Casals, Ferran
AU - Idaghdour, Youssef
AU - Keebler, John
AU - Stone, Eric A.
AU - Zilversmit, Martine
AU - Jorde, Lynn
AU - Xing, Jinchuan
AU - Eichler, Evan E.
AU - Aksay, Gozde
AU - Alkan, Can
AU - Hajirasouliha, Iman
AU - Hormozdiari, Fereydoun
AU - Kidd, Jeffrey M.
AU - CenkSahinalp, S.
AU - Sudmant, Peter H.
AU - Chen, Ken
AU - Chinwalla, Asif
AU - Ding, Li
AU - Koboldt, Daniel C.
AU - McLellan, Mike D.
AU - Wallis, John W.
AU - Wendl, Michael C.
AU - Zhang, Qunyuan
AU - Albers, Cornelis A.
AU - Ayub, Qasim
AU - Balasubramaniam, Senduran
AU - Barrett, Jeffrey C.
AU - Chen, Yuan
AU - Conrad, Donald F.
AU - Danecek, Petr
AU - Dermitzakis, Emmanouil T.
AU - Hu, Min
AU - Huang, Ni
AU - Matt, E. Hurles
AU - Jin, Hanjun
AU - Jostins, Luke
AU - Keane, Thomas M.
AU - Quang Le, Si
AU - Lindsay, Sarah
AU - Long, Quan
AU - MacArthur, Daniel G.
AU - Montgomery, Stephen B.
AU - Parts, Leopold
AU - Chris Tyler-Smith, Tyler-Smith
AU - Walter, Klaudia
AU - Zhang, Yujun
AU - Gerstein, Mark B.
AU - Snyder, Michael
AU - Abyzov, Alexej
AU - Balasubramanian, Suganthi
AU - Bjornson, Robert
AU - Grubert, Fabian
AU - Habegger, Lukas
AU - Haraksingh, Rajini
AU - Khurana, Ekta
AU - Lam, Hugo Y.K.
AU - Leng, Jing
AU - Mu, Xinmeng Jasmine
AU - Urban, Alexander E.
AU - Zhang, Zhengdong
AU - McCarroll, Steven A.
AU - Zheng-Bradley, Xiangqun
AU - Batzer, Mark A.
AU - Hurles, Matt E.
AU - Du, Jiang
AU - Jee, Justin
AU - Coafra, Cristian
AU - Dinh, Huyen
AU - Kovar, Christie
AU - Lee, Sandy
AU - Nazareth, Lynne
AU - Wilkinson, Jane
AU - Coffey, Allison
AU - Scott, Carol
AU - Tyler-Smith, Chris
AU - Gharani, Neda
AU - Kaye, Jane S.
AU - Kent, Alastair
AU - Li, Taosha
AU - McGuire, Amy L.
AU - Ossorio, Pilar N.
AU - Rotimi, Charles N.
AU - Su, Yeyang
AU - Toji, Lorraine H.
AU - Felsenfeld, Adam L.
AU - McEwen, Jean E.
AU - Abdallah, Assya
AU - Juenger, Christopher R.
AU - Clemm, Nicholas C.
AU - Duncanson, Audrey
AU - Green, Eric D.
AU - Guyer, Mark S.
AU - Peterson, Jane L.
PY - 2010/10/28
Y1 - 2010/10/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84975742565&partnerID=8YFLogxK
U2 - 10.1038/nature09534
DO - 10.1038/nature09534
M3 - Article
SN - 0028-0836
VL - 467
SP - 1061
EP - 1073
JO - Nature
JF - Nature
IS - 7319
ER -