Mapping copy number variation by population-scale genome sequencing

Ryan E. Mills, Klaudia Walter, Chip Stewart, Robert E. Handsaker, Ken Chen, Can Alkan, Alexej Abyzov, Seungtai Chris Yoon, Kai Ye, R. Keira Cheetham, Asif Chinwalla, Donald F. Conrad, Yutao Fu, Fabian Grubert, Iman Hajirasouliha, Fereydoun Hormozdiari, Lilia M. Iakoucheva, Zamin Iqbal, Shuli Kang, Jeffrey M. Kidd & 353 others Miriam K. Konkel, Joshua Korn, Ekta Khurana, Deniz Kural, Hugo Y.K. Lam, Jing Leng, Ruiqiang Li, Yingrui Li, Chang Yun Lin, Ruibang Luo, Xinmeng Jasmine Mu, James Nemesh, Heather E. Peckham, Tobias Rausch, Aylwyn Scally, Xinghua Shi, Michael P. Stromberg, Adrian M. Sütz, Alexander Eckehart Urban, Jerilyn A. Walker, Jiantao Wu, Yujun Zhang, Zhengdong D. Zhang, Mark A. Batzer, Li Ding, Gabor T. Marth, Gil McVean, Jonathan Sebat, Michael Snyder, Jun Wang, Kenny Ye, Evan E. Eichler, Mark B. Gerstein, Matthew E. Hurles, Charles Lee, Steven A. McCarroll, Jan O. Korbel, Francis S. Collins, D. L. Altshuler, R. M. Durbin, G. R. Abecasis, D. R. Bentley, A. Chakravarti, A. G. Clark, F. M. De La Vega, P. Donnelly, M. Egholm, P. Flicek, S. B. Gabriel, R. A. Gibbs, B. M. Knoppers, E. S. Lander, H. Lehrach, E. R. Mardis, G. A. McVean, D. A. Nickerson, L. Peltonen, A. J. Schafer, S. T. Sherry, R. K. Wilson, D. Deiros, M. Metzker, D. Muzny, J. Reid, D. Wheeler, J. Li, M. Jian, G. Li, H. Liang, G. Tian, B. Wang, W. Wang, H. Yang, X. Zhang, H. Zheng, L. Ambrogio, T. Bloom, K. Cibulskis, T. J. Fennell, D. B. Jaffe, E. Shefler, C. L. Sougnez, N. Gormley, S. Humphray, Z. Kingsbury, P. Koko-Gonzales, J. Stone, K. J. McKernan, G. L. Costa, J. K. Ichikawa, C. C. Lee, R. Sudbrak, T. A. Borodina, A. Dahl, A. N. Davydov, P. Marquardt, F. Mertes, W. Nietfeld, P. Rosenstiel, S. Schreiber, A. V. Soldatov, B. Timmermann, M. Tolzmann, J. Affourtit, D. Ashworth, S. Attiya, M. Bachorski, E. Buglione, A. Burke, A. Caprio, C. Celone, S. Clark, D. Conners, B. Desany, L. Gu, L. Guccione, K. Kao, A. Kebbel, J. Knowlton, M. Labrecque, L. McDade, C. Mealmaker, M. Minderman, A. Nawrocki, F. Niazi, K. Pareja, R. Ramenani, D. Riches, W. Song, C. Turcotte, S. Wang, D. Dooling, L. Fulton, R. Fulton, G. Weinstock, J. Burton, D. M. Carter, C. Churcher, A. Coffey, A. Cox, A. Palotie, M. Quail, T. Skelly, J. Stalker, H. P. Swerdlow, D. Turner, A. De Witte, S. Giles, M. Bainbridge, D. Challis, A. Sabo, F. Yu, J. Yu, X. Fang, X. Guo, S. Tai, H. Wu, X. Zheng, Y. Zhou, E. P. Garrison, W. Huang, A. Indap, W. P. Lee, W. F. Leong, A. R. Quinlan, A. N. Ward, M. J. Daly, M. A. DePristo, A. D. Ball, E. Banks, B. L. Browning, K. V. Garimella, S. R. Grossman, M. Hanna, C. Hartl, A. M. Kernytsky, J. M. Korn, H. Li, J. R. Maguire, A. McKenna, J. C. Nemesh, A. A. Philippakis, R. E. Poplin, A. Price, M. A. Rivas, P. C. Sabeti, S. F. Schaffner, I. A. Shlyakhter, D. N. Cooper, E. V. Ball, M. Mort, A. D. Phillips, P. D. Stenson, V. Makarov, C. D. Bustamante, A. Boyko, J. Degenhardt, S. Gravel, Ryan N Gutenkunst, M. Kaganovich, A. Keinan, P. Lacroute, X. Ma, A. Reynolds, L. Clarke, F. Cunningham, J. Herrero, S. Keenen, E. Kulesha, R. Leinonen, W. M. McLaren, R. Radhakrishnan, R. E. Smith, V. Zalunin, X. Zheng-Bradley, A. M. Stütz, M. Bauer, T. Cox, M. Eberle, T. James, S. Kahn, L. Murray, F. C. Hyland, J. M. Manning, S. F. McLaughlin, O. Sakarya, Y. A. Sun, E. F. Tsung, M. W. Albrecht, V. S. Amstislavskiy, R. Herwig, D. V. Parkhomchuk, R. Agarwala, H. Khouri, A. O. Morgulis, J. E. Paschall, L. D. Phan, K. E. Rotmistrovsky, R. D. Sanders, M. F. Shumway, C. Xiao, A. Auton, G. Lunter, J. L. Marchini, L. Moutsianas, S. Myers, A. Tumian, J. Knight, R. Winer, D. W. Craig, S. M. Beckstrom-Sternberg, A. Christoforides, A. A. Kurdoglu, J. V. Pearson, S. A. Sinari, W. D. Tembe, D. Haussler, A. S. Hinrichs, S. J. Katzman, A. Kern, R. M. Kuhn, M. Przeworski, R. D. Hernandez, B. Howie, J. L. Kelley, S. C. Melton, P. Anderson, T. Blackwell, W. Chen, W. O. Cookson, J. Ding, H. M. Kang, M. Lathrop, L. Liang, M. F. Moffatt, P. Scheet, C. Sidore, X. Zhan, S. Zöllner, P. Awadalla, F. Casals, Y. Idaghdour, J. Keebler, E. A. Stone, M. Zilversmit, L. Jorde, J. Xing, G. Aksay, S. C. Sahinalp, P. H. Sudmant, D. C. Koboldt, M. D. McLellan, J. W. Wallis, M. C. Wendl, Q. Zhang, C. A. Albers, Q. Ayub, S. Balasubramaniam, J. C. Barrett, Y. Chen, P. Danecek, E. T. Dermitzakis, M. Hu, N. Huang, H. Jin, L. Jostins, T. M. Keane, S. Q. Le, S. Lindsay, Q. Long, D. G. MacArthur, S. B. Montgomery, L. Parts, C. Tyler-Smith, S. Balasubramanian, R. Bjornson, J. Du, L. Habegger, R. Haraksingh, J. Jee, H. Y. Lam, J. Jeng, Z. Zhang, E. Bank, S. Yoon, J. Kidd, C. Coafra, H. Dinh, C. Kovar, S. Lee, L. Nazareth, J. Wilkinson, H. M. Khouri, C. Scott, N. Gharani, J. S. Kaye, A. Kent, T. Li, A. L. McGuire, P. N. Ossorio, C. N. Rotimi, Y. Su, L. H. Toji, L. D. Brooks, A. L. Felsenfeld, J. E. McEwen, A. Abdallah, C. R. Juenger, N. C. Clemm, A. Duncanson, E. D. Green, M. S. Guyer, J. L. Peterson

Research output: Contribution to journalArticle

678 Citations (Scopus)

Abstract

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalNature
Volume470
Issue number7332
DOIs
StatePublished - Feb 3 2011
Externally publishedYes

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Genomic Structural Variation
Nucleotides
Genome
Gene Deletion
Human Genome
DNA Sequence Analysis
Population
Genes

ASJC Scopus subject areas

  • General

Cite this

Mills, R. E., Walter, K., Stewart, C., Handsaker, R. E., Chen, K., Alkan, C., ... Peterson, J. L. (2011). Mapping copy number variation by population-scale genome sequencing. Nature, 470(7332), 59-65. https://doi.org/10.1038/nature09708

Mapping copy number variation by population-scale genome sequencing. / Mills, Ryan E.; Walter, Klaudia; Stewart, Chip; Handsaker, Robert E.; Chen, Ken; Alkan, Can; Abyzov, Alexej; Yoon, Seungtai Chris; Ye, Kai; Cheetham, R. Keira; Chinwalla, Asif; Conrad, Donald F.; Fu, Yutao; Grubert, Fabian; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Iakoucheva, Lilia M.; Iqbal, Zamin; Kang, Shuli; Kidd, Jeffrey M.; Konkel, Miriam K.; Korn, Joshua; Khurana, Ekta; Kural, Deniz; Lam, Hugo Y.K.; Leng, Jing; Li, Ruiqiang; Li, Yingrui; Lin, Chang Yun; Luo, Ruibang; Mu, Xinmeng Jasmine; Nemesh, James; Peckham, Heather E.; Rausch, Tobias; Scally, Aylwyn; Shi, Xinghua; Stromberg, Michael P.; Sütz, Adrian M.; Urban, Alexander Eckehart; Walker, Jerilyn A.; Wu, Jiantao; Zhang, Yujun; Zhang, Zhengdong D.; Batzer, Mark A.; Ding, Li; Marth, Gabor T.; McVean, Gil; Sebat, Jonathan; Snyder, Michael; Wang, Jun; Ye, Kenny; Eichler, Evan E.; Gerstein, Mark B.; Hurles, Matthew E.; Lee, Charles; McCarroll, Steven A.; Korbel, Jan O.; Collins, Francis S.; Altshuler, D. L.; Durbin, R. M.; Abecasis, G. R.; Bentley, D. R.; Chakravarti, A.; Clark, A. G.; De La Vega, F. M.; Donnelly, P.; Egholm, M.; Flicek, P.; Gabriel, S. B.; Gibbs, R. A.; Knoppers, B. M.; Lander, E. S.; Lehrach, H.; Mardis, E. R.; McVean, G. A.; Nickerson, D. A.; Peltonen, L.; Schafer, A. J.; Sherry, S. T.; Wilson, R. K.; Deiros, D.; Metzker, M.; Muzny, D.; Reid, J.; Wheeler, D.; Li, J.; Jian, M.; Li, G.; Liang, H.; Tian, G.; Wang, B.; Wang, W.; Yang, H.; Zhang, X.; Zheng, H.; Ambrogio, L.; Bloom, T.; Cibulskis, K.; Fennell, T. J.; Jaffe, D. B.; Shefler, E.; Sougnez, C. L.; Gormley, N.; Humphray, S.; Kingsbury, Z.; Koko-Gonzales, P.; Stone, J.; McKernan, K. J.; Costa, G. L.; Ichikawa, J. K.; Lee, C. C.; Sudbrak, R.; Borodina, T. A.; Dahl, A.; Davydov, A. N.; Marquardt, P.; Mertes, F.; Nietfeld, W.; Rosenstiel, P.; Schreiber, S.; Soldatov, A. V.; Timmermann, B.; Tolzmann, M.; Affourtit, J.; Ashworth, D.; Attiya, S.; Bachorski, M.; Buglione, E.; Burke, A.; Caprio, A.; Celone, C.; Clark, S.; Conners, D.; Desany, B.; Gu, L.; Guccione, L.; Kao, K.; Kebbel, A.; Knowlton, J.; Labrecque, M.; McDade, L.; Mealmaker, C.; Minderman, M.; Nawrocki, A.; Niazi, F.; Pareja, K.; Ramenani, R.; Riches, D.; Song, W.; Turcotte, C.; Wang, S.; Dooling, D.; Fulton, L.; Fulton, R.; Weinstock, G.; Burton, J.; Carter, D. M.; Churcher, C.; Coffey, A.; Cox, A.; Palotie, A.; Quail, M.; Skelly, T.; Stalker, J.; Swerdlow, H. P.; Turner, D.; De Witte, A.; Giles, S.; Bainbridge, M.; Challis, D.; Sabo, A.; Yu, F.; Yu, J.; Fang, X.; Guo, X.; Tai, S.; Wu, H.; Zheng, X.; Zhou, Y.; Garrison, E. P.; Huang, W.; Indap, A.; Lee, W. P.; Leong, W. F.; Quinlan, A. R.; Ward, A. N.; Daly, M. J.; DePristo, M. A.; Ball, A. D.; Banks, E.; Browning, B. L.; Garimella, K. V.; Grossman, S. R.; Hanna, M.; Hartl, C.; Kernytsky, A. M.; Korn, J. M.; Li, H.; Maguire, J. R.; McKenna, A.; Nemesh, J. C.; Philippakis, A. A.; Poplin, R. E.; Price, A.; Rivas, M. A.; Sabeti, P. C.; Schaffner, S. F.; Shlyakhter, I. A.; Cooper, D. N.; Ball, E. V.; Mort, M.; Phillips, A. D.; Stenson, P. D.; Makarov, V.; Bustamante, C. D.; Boyko, A.; Degenhardt, J.; Gravel, S.; Gutenkunst, Ryan N; Kaganovich, M.; Keinan, A.; Lacroute, P.; Ma, X.; Reynolds, A.; Clarke, L.; Cunningham, F.; Herrero, J.; Keenen, S.; Kulesha, E.; Leinonen, R.; McLaren, W. M.; Radhakrishnan, R.; Smith, R. E.; Zalunin, V.; Zheng-Bradley, X.; Stütz, A. M.; Bauer, M.; Cox, T.; Eberle, M.; James, T.; Kahn, S.; Murray, L.; Hyland, F. C.; Manning, J. M.; McLaughlin, S. F.; Sakarya, O.; Sun, Y. A.; Tsung, E. F.; Albrecht, M. W.; Amstislavskiy, V. S.; Herwig, R.; Parkhomchuk, D. V.; Agarwala, R.; Khouri, H.; Morgulis, A. O.; Paschall, J. E.; Phan, L. D.; Rotmistrovsky, K. E.; Sanders, R. D.; Shumway, M. F.; Xiao, C.; Auton, A.; Lunter, G.; Marchini, J. L.; Moutsianas, L.; Myers, S.; Tumian, A.; Knight, J.; Winer, R.; Craig, D. W.; Beckstrom-Sternberg, S. M.; Christoforides, A.; Kurdoglu, A. A.; Pearson, J. V.; Sinari, S. A.; Tembe, W. D.; Haussler, D.; Hinrichs, A. S.; Katzman, S. J.; Kern, A.; Kuhn, R. M.; Przeworski, M.; Hernandez, R. D.; Howie, B.; Kelley, J. L.; Melton, S. C.; Anderson, P.; Blackwell, T.; Chen, W.; Cookson, W. O.; Ding, J.; Kang, H. M.; Lathrop, M.; Liang, L.; Moffatt, M. F.; Scheet, P.; Sidore, C.; Zhan, X.; Zöllner, S.; Awadalla, P.; Casals, F.; Idaghdour, Y.; Keebler, J.; Stone, E. A.; Zilversmit, M.; Jorde, L.; Xing, J.; Aksay, G.; Sahinalp, S. C.; Sudmant, P. H.; Koboldt, D. C.; McLellan, M. D.; Wallis, J. W.; Wendl, M. C.; Zhang, Q.; Albers, C. A.; Ayub, Q.; Balasubramaniam, S.; Barrett, J. C.; Chen, Y.; Danecek, P.; Dermitzakis, E. T.; Hu, M.; Huang, N.; Jin, H.; Jostins, L.; Keane, T. M.; Le, S. Q.; Lindsay, S.; Long, Q.; MacArthur, D. G.; Montgomery, S. B.; Parts, L.; Tyler-Smith, C.; Balasubramanian, S.; Bjornson, R.; Du, J.; Habegger, L.; Haraksingh, R.; Jee, J.; Lam, H. Y.; Jeng, J.; Zhang, Z.; Bank, E.; Yoon, S.; Kidd, J.; Coafra, C.; Dinh, H.; Kovar, C.; Lee, S.; Nazareth, L.; Wilkinson, J.; Khouri, H. M.; Scott, C.; Gharani, N.; Kaye, J. S.; Kent, A.; Li, T.; McGuire, A. L.; Ossorio, P. N.; Rotimi, C. N.; Su, Y.; Toji, L. H.; Brooks, L. D.; Felsenfeld, A. L.; McEwen, J. E.; Abdallah, A.; Juenger, C. R.; Clemm, N. C.; Duncanson, A.; Green, E. D.; Guyer, M. S.; Peterson, J. L.

In: Nature, Vol. 470, No. 7332, 03.02.2011, p. 59-65.

Research output: Contribution to journalArticle

Mills, RE, Walter, K, Stewart, C, Handsaker, RE, Chen, K, Alkan, C, Abyzov, A, Yoon, SC, Ye, K, Cheetham, RK, Chinwalla, A, Conrad, DF, Fu, Y, Grubert, F, Hajirasouliha, I, Hormozdiari, F, Iakoucheva, LM, Iqbal, Z, Kang, S, Kidd, JM, Konkel, MK, Korn, J, Khurana, E, Kural, D, Lam, HYK, Leng, J, Li, R, Li, Y, Lin, CY, Luo, R, Mu, XJ, Nemesh, J, Peckham, HE, Rausch, T, Scally, A, Shi, X, Stromberg, MP, Sütz, AM, Urban, AE, Walker, JA, Wu, J, Zhang, Y, Zhang, ZD, Batzer, MA, Ding, L, Marth, GT, McVean, G, Sebat, J, Snyder, M, Wang, J, Ye, K, Eichler, EE, Gerstein, MB, Hurles, ME, Lee, C, McCarroll, SA, Korbel, JO, Collins, FS, Altshuler, DL, Durbin, RM, Abecasis, GR, Bentley, DR, Chakravarti, A, Clark, AG, De La Vega, FM, Donnelly, P, Egholm, M, Flicek, P, Gabriel, SB, Gibbs, RA, Knoppers, BM, Lander, ES, Lehrach, H, Mardis, ER, McVean, GA, Nickerson, DA, Peltonen, L, Schafer, AJ, Sherry, ST, Wilson, RK, Deiros, D, Metzker, M, Muzny, D, Reid, J, Wheeler, D, Li, J, Jian, M, Li, G, Liang, H, Tian, G, Wang, B, Wang, W, Yang, H, Zhang, X, Zheng, H, Ambrogio, L, Bloom, T, Cibulskis, K, Fennell, TJ, Jaffe, DB, Shefler, E, Sougnez, CL, Gormley, N, Humphray, S, Kingsbury, Z, Koko-Gonzales, P, Stone, J, McKernan, KJ, Costa, GL, Ichikawa, JK, Lee, CC, Sudbrak, R, Borodina, TA, Dahl, A, Davydov, AN, Marquardt, P, Mertes, F, Nietfeld, W, Rosenstiel, P, Schreiber, S, Soldatov, AV, Timmermann, B, Tolzmann, M, Affourtit, J, Ashworth, D, Attiya, S, Bachorski, M, Buglione, E, Burke, A, Caprio, A, Celone, C, Clark, S, Conners, D, Desany, B, Gu, L, Guccione, L, Kao, K, Kebbel, A, Knowlton, J, Labrecque, M, McDade, L, Mealmaker, C, Minderman, M, Nawrocki, A, Niazi, F, Pareja, K, Ramenani, R, Riches, D, Song, W, Turcotte, C, Wang, S, Dooling, D, Fulton, L, Fulton, R, Weinstock, G, Burton, J, Carter, DM, Churcher, C, Coffey, A, Cox, A, Palotie, A, Quail, M, Skelly, T, Stalker, J, Swerdlow, HP, Turner, D, De Witte, A, Giles, S, Bainbridge, M, Challis, D, Sabo, A, Yu, F, Yu, J, Fang, X, Guo, X, Tai, S, Wu, H, Zheng, X, Zhou, Y, Garrison, EP, Huang, W, Indap, A, Lee, WP, Leong, WF, Quinlan, AR, Ward, AN, Daly, MJ, DePristo, MA, Ball, AD, Banks, E, Browning, BL, Garimella, KV, Grossman, SR, Hanna, M, Hartl, C, Kernytsky, AM, Korn, JM, Li, H, Maguire, JR, McKenna, A, Nemesh, JC, Philippakis, AA, Poplin, RE, Price, A, Rivas, MA, Sabeti, PC, Schaffner, SF, Shlyakhter, IA, Cooper, DN, Ball, EV, Mort, M, Phillips, AD, Stenson, PD, Makarov, V, Bustamante, CD, Boyko, A, Degenhardt, J, Gravel, S, Gutenkunst, RN, Kaganovich, M, Keinan, A, Lacroute, P, Ma, X, Reynolds, A, Clarke, L, Cunningham, F, Herrero, J, Keenen, S, Kulesha, E, Leinonen, R, McLaren, WM, Radhakrishnan, R, Smith, RE, Zalunin, V, Zheng-Bradley, X, Stütz, AM, Bauer, M, Cox, T, Eberle, M, James, T, Kahn, S, Murray, L, Hyland, FC, Manning, JM, McLaughlin, SF, Sakarya, O, Sun, YA, Tsung, EF, Albrecht, MW, Amstislavskiy, VS, Herwig, R, Parkhomchuk, DV, Agarwala, R, Khouri, H, Morgulis, AO, Paschall, JE, Phan, LD, Rotmistrovsky, KE, Sanders, RD, Shumway, MF, Xiao, C, Auton, A, Lunter, G, Marchini, JL, Moutsianas, L, Myers, S, Tumian, A, Knight, J, Winer, R, Craig, DW, Beckstrom-Sternberg, SM, Christoforides, A, Kurdoglu, AA, Pearson, JV, Sinari, SA, Tembe, WD, Haussler, D, Hinrichs, AS, Katzman, SJ, Kern, A, Kuhn, RM, Przeworski, M, Hernandez, RD, Howie, B, Kelley, JL, Melton, SC, Anderson, P, Blackwell, T, Chen, W, Cookson, WO, Ding, J, Kang, HM, Lathrop, M, Liang, L, Moffatt, MF, Scheet, P, Sidore, C, Zhan, X, Zöllner, S, Awadalla, P, Casals, F, Idaghdour, Y, Keebler, J, Stone, EA, Zilversmit, M, Jorde, L, Xing, J, Aksay, G, Sahinalp, SC, Sudmant, PH, Koboldt, DC, McLellan, MD, Wallis, JW, Wendl, MC, Zhang, Q, Albers, CA, Ayub, Q, Balasubramaniam, S, Barrett, JC, Chen, Y, Danecek, P, Dermitzakis, ET, Hu, M, Huang, N, Jin, H, Jostins, L, Keane, TM, Le, SQ, Lindsay, S, Long, Q, MacArthur, DG, Montgomery, SB, Parts, L, Tyler-Smith, C, Balasubramanian, S, Bjornson, R, Du, J, Habegger, L, Haraksingh, R, Jee, J, Lam, HY, Jeng, J, Zhang, Z, Bank, E, Yoon, S, Kidd, J, Coafra, C, Dinh, H, Kovar, C, Lee, S, Nazareth, L, Wilkinson, J, Khouri, HM, Scott, C, Gharani, N, Kaye, JS, Kent, A, Li, T, McGuire, AL, Ossorio, PN, Rotimi, CN, Su, Y, Toji, LH, Brooks, LD, Felsenfeld, AL, McEwen, JE, Abdallah, A, Juenger, CR, Clemm, NC, Duncanson, A, Green, ED, Guyer, MS & Peterson, JL 2011, 'Mapping copy number variation by population-scale genome sequencing', Nature, vol. 470, no. 7332, pp. 59-65. https://doi.org/10.1038/nature09708
Mills RE, Walter K, Stewart C, Handsaker RE, Chen K, Alkan C et al. Mapping copy number variation by population-scale genome sequencing. Nature. 2011 Feb 3;470(7332):59-65. https://doi.org/10.1038/nature09708
Mills, Ryan E. ; Walter, Klaudia ; Stewart, Chip ; Handsaker, Robert E. ; Chen, Ken ; Alkan, Can ; Abyzov, Alexej ; Yoon, Seungtai Chris ; Ye, Kai ; Cheetham, R. Keira ; Chinwalla, Asif ; Conrad, Donald F. ; Fu, Yutao ; Grubert, Fabian ; Hajirasouliha, Iman ; Hormozdiari, Fereydoun ; Iakoucheva, Lilia M. ; Iqbal, Zamin ; Kang, Shuli ; Kidd, Jeffrey M. ; Konkel, Miriam K. ; Korn, Joshua ; Khurana, Ekta ; Kural, Deniz ; Lam, Hugo Y.K. ; Leng, Jing ; Li, Ruiqiang ; Li, Yingrui ; Lin, Chang Yun ; Luo, Ruibang ; Mu, Xinmeng Jasmine ; Nemesh, James ; Peckham, Heather E. ; Rausch, Tobias ; Scally, Aylwyn ; Shi, Xinghua ; Stromberg, Michael P. ; Sütz, Adrian M. ; Urban, Alexander Eckehart ; Walker, Jerilyn A. ; Wu, Jiantao ; Zhang, Yujun ; Zhang, Zhengdong D. ; Batzer, Mark A. ; Ding, Li ; Marth, Gabor T. ; McVean, Gil ; Sebat, Jonathan ; Snyder, Michael ; Wang, Jun ; Ye, Kenny ; Eichler, Evan E. ; Gerstein, Mark B. ; Hurles, Matthew E. ; Lee, Charles ; McCarroll, Steven A. ; Korbel, Jan O. ; Collins, Francis S. ; Altshuler, D. L. ; Durbin, R. M. ; Abecasis, G. R. ; Bentley, D. R. ; Chakravarti, A. ; Clark, A. G. ; De La Vega, F. M. ; Donnelly, P. ; Egholm, M. ; Flicek, P. ; Gabriel, S. B. ; Gibbs, R. A. ; Knoppers, B. M. ; Lander, E. S. ; Lehrach, H. ; Mardis, E. R. ; McVean, G. A. ; Nickerson, D. A. ; Peltonen, L. ; Schafer, A. J. ; Sherry, S. T. ; Wilson, R. K. ; Deiros, D. ; Metzker, M. ; Muzny, D. ; Reid, J. ; Wheeler, D. ; Li, J. ; Jian, M. ; Li, G. ; Liang, H. ; Tian, G. ; Wang, B. ; Wang, W. ; Yang, H. ; Zhang, X. ; Zheng, H. ; Ambrogio, L. ; Bloom, T. ; Cibulskis, K. ; Fennell, T. J. ; Jaffe, D. B. ; Shefler, E. ; Sougnez, C. L. ; Gormley, N. ; Humphray, S. ; Kingsbury, Z. ; Koko-Gonzales, P. ; Stone, J. ; McKernan, K. J. ; Costa, G. L. ; Ichikawa, J. K. ; Lee, C. C. ; Sudbrak, R. ; Borodina, T. A. ; Dahl, A. ; Davydov, A. N. ; Marquardt, P. ; Mertes, F. ; Nietfeld, W. ; Rosenstiel, P. ; Schreiber, S. ; Soldatov, A. V. ; Timmermann, B. ; Tolzmann, M. ; Affourtit, J. ; Ashworth, D. ; Attiya, S. ; Bachorski, M. ; Buglione, E. ; Burke, A. ; Caprio, A. ; Celone, C. ; Clark, S. ; Conners, D. ; Desany, B. ; Gu, L. ; Guccione, L. ; Kao, K. ; Kebbel, A. ; Knowlton, J. ; Labrecque, M. ; McDade, L. ; Mealmaker, C. ; Minderman, M. ; Nawrocki, A. ; Niazi, F. ; Pareja, K. ; Ramenani, R. ; Riches, D. ; Song, W. ; Turcotte, C. ; Wang, S. ; Dooling, D. ; Fulton, L. ; Fulton, R. ; Weinstock, G. ; Burton, J. ; Carter, D. M. ; Churcher, C. ; Coffey, A. ; Cox, A. ; Palotie, A. ; Quail, M. ; Skelly, T. ; Stalker, J. ; Swerdlow, H. P. ; Turner, D. ; De Witte, A. ; Giles, S. ; Bainbridge, M. ; Challis, D. ; Sabo, A. ; Yu, F. ; Yu, J. ; Fang, X. ; Guo, X. ; Tai, S. ; Wu, H. ; Zheng, X. ; Zhou, Y. ; Garrison, E. P. ; Huang, W. ; Indap, A. ; Lee, W. P. ; Leong, W. F. ; Quinlan, A. R. ; Ward, A. N. ; Daly, M. J. ; DePristo, M. A. ; Ball, A. D. ; Banks, E. ; Browning, B. L. ; Garimella, K. V. ; Grossman, S. R. ; Hanna, M. ; Hartl, C. ; Kernytsky, A. M. ; Korn, J. M. ; Li, H. ; Maguire, J. R. ; McKenna, A. ; Nemesh, J. C. ; Philippakis, A. A. ; Poplin, R. E. ; Price, A. ; Rivas, M. A. ; Sabeti, P. C. ; Schaffner, S. F. ; Shlyakhter, I. A. ; Cooper, D. N. ; Ball, E. V. ; Mort, M. ; Phillips, A. D. ; Stenson, P. D. ; Makarov, V. ; Bustamante, C. D. ; Boyko, A. ; Degenhardt, J. ; Gravel, S. ; Gutenkunst, Ryan N ; Kaganovich, M. ; Keinan, A. ; Lacroute, P. ; Ma, X. ; Reynolds, A. ; Clarke, L. ; Cunningham, F. ; Herrero, J. ; Keenen, S. ; Kulesha, E. ; Leinonen, R. ; McLaren, W. M. ; Radhakrishnan, R. ; Smith, R. E. ; Zalunin, V. ; Zheng-Bradley, X. ; Stütz, A. M. ; Bauer, M. ; Cox, T. ; Eberle, M. ; James, T. ; Kahn, S. ; Murray, L. ; Hyland, F. C. ; Manning, J. M. ; McLaughlin, S. F. ; Sakarya, O. ; Sun, Y. A. ; Tsung, E. F. ; Albrecht, M. W. ; Amstislavskiy, V. S. ; Herwig, R. ; Parkhomchuk, D. V. ; Agarwala, R. ; Khouri, H. ; Morgulis, A. O. ; Paschall, J. E. ; Phan, L. D. ; Rotmistrovsky, K. E. ; Sanders, R. D. ; Shumway, M. F. ; Xiao, C. ; Auton, A. ; Lunter, G. ; Marchini, J. L. ; Moutsianas, L. ; Myers, S. ; Tumian, A. ; Knight, J. ; Winer, R. ; Craig, D. W. ; Beckstrom-Sternberg, S. M. ; Christoforides, A. ; Kurdoglu, A. A. ; Pearson, J. V. ; Sinari, S. A. ; Tembe, W. D. ; Haussler, D. ; Hinrichs, A. S. ; Katzman, S. J. ; Kern, A. ; Kuhn, R. M. ; Przeworski, M. ; Hernandez, R. D. ; Howie, B. ; Kelley, J. L. ; Melton, S. C. ; Anderson, P. ; Blackwell, T. ; Chen, W. ; Cookson, W. O. ; Ding, J. ; Kang, H. M. ; Lathrop, M. ; Liang, L. ; Moffatt, M. F. ; Scheet, P. ; Sidore, C. ; Zhan, X. ; Zöllner, S. ; Awadalla, P. ; Casals, F. ; Idaghdour, Y. ; Keebler, J. ; Stone, E. A. ; Zilversmit, M. ; Jorde, L. ; Xing, J. ; Aksay, G. ; Sahinalp, S. C. ; Sudmant, P. H. ; Koboldt, D. C. ; McLellan, M. D. ; Wallis, J. W. ; Wendl, M. C. ; Zhang, Q. ; Albers, C. A. ; Ayub, Q. ; Balasubramaniam, S. ; Barrett, J. C. ; Chen, Y. ; Danecek, P. ; Dermitzakis, E. T. ; Hu, M. ; Huang, N. ; Jin, H. ; Jostins, L. ; Keane, T. M. ; Le, S. Q. ; Lindsay, S. ; Long, Q. ; MacArthur, D. G. ; Montgomery, S. B. ; Parts, L. ; Tyler-Smith, C. ; Balasubramanian, S. ; Bjornson, R. ; Du, J. ; Habegger, L. ; Haraksingh, R. ; Jee, J. ; Lam, H. Y. ; Jeng, J. ; Zhang, Z. ; Bank, E. ; Yoon, S. ; Kidd, J. ; Coafra, C. ; Dinh, H. ; Kovar, C. ; Lee, S. ; Nazareth, L. ; Wilkinson, J. ; Khouri, H. M. ; Scott, C. ; Gharani, N. ; Kaye, J. S. ; Kent, A. ; Li, T. ; McGuire, A. L. ; Ossorio, P. N. ; Rotimi, C. N. ; Su, Y. ; Toji, L. H. ; Brooks, L. D. ; Felsenfeld, A. L. ; McEwen, J. E. ; Abdallah, A. ; Juenger, C. R. ; Clemm, N. C. ; Duncanson, A. ; Green, E. D. ; Guyer, M. S. ; Peterson, J. L. / Mapping copy number variation by population-scale genome sequencing. In: Nature. 2011 ; Vol. 470, No. 7332. pp. 59-65.
@article{aa41b8d81d324adeb014872bcfc1bb5e,
title = "Mapping copy number variation by population-scale genome sequencing",
abstract = "Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53{\%}) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.",
author = "Mills, {Ryan E.} and Klaudia Walter and Chip Stewart and Handsaker, {Robert E.} and Ken Chen and Can Alkan and Alexej Abyzov and Yoon, {Seungtai Chris} and Kai Ye and Cheetham, {R. Keira} and Asif Chinwalla and Conrad, {Donald F.} and Yutao Fu and Fabian Grubert and Iman Hajirasouliha and Fereydoun Hormozdiari and Iakoucheva, {Lilia M.} and Zamin Iqbal and Shuli Kang and Kidd, {Jeffrey M.} and Konkel, {Miriam K.} and Joshua Korn and Ekta Khurana and Deniz Kural and Lam, {Hugo Y.K.} and Jing Leng and Ruiqiang Li and Yingrui Li and Lin, {Chang Yun} and Ruibang Luo and Mu, {Xinmeng Jasmine} and James Nemesh and Peckham, {Heather E.} and Tobias Rausch and Aylwyn Scally and Xinghua Shi and Stromberg, {Michael P.} and S{\"u}tz, {Adrian M.} and Urban, {Alexander Eckehart} and Walker, {Jerilyn A.} and Jiantao Wu and Yujun Zhang and Zhang, {Zhengdong D.} and Batzer, {Mark A.} and Li Ding and Marth, {Gabor T.} and Gil McVean and Jonathan Sebat and Michael Snyder and Jun Wang and Kenny Ye and Eichler, {Evan E.} and Gerstein, {Mark B.} and Hurles, {Matthew E.} and Charles Lee and McCarroll, {Steven A.} and Korbel, {Jan O.} and Collins, {Francis S.} and Altshuler, {D. L.} and Durbin, {R. M.} and Abecasis, {G. R.} and Bentley, {D. R.} and A. Chakravarti and Clark, {A. G.} and {De La Vega}, {F. M.} and P. Donnelly and M. Egholm and P. Flicek and Gabriel, {S. B.} and Gibbs, {R. A.} and Knoppers, {B. M.} and Lander, {E. S.} and H. Lehrach and Mardis, {E. R.} and McVean, {G. A.} and Nickerson, {D. A.} and L. Peltonen and Schafer, {A. J.} and Sherry, {S. T.} and Wilson, {R. K.} and D. Deiros and M. Metzker and D. Muzny and J. Reid and D. Wheeler and J. Li and M. Jian and G. Li and H. Liang and G. Tian and B. Wang and W. Wang and H. Yang and X. Zhang and H. Zheng and L. Ambrogio and T. Bloom and K. Cibulskis and Fennell, {T. J.} and Jaffe, {D. B.} and E. Shefler and Sougnez, {C. L.} and N. Gormley and S. Humphray and Z. Kingsbury and P. Koko-Gonzales and J. Stone and McKernan, {K. J.} and Costa, {G. L.} and Ichikawa, {J. K.} and Lee, {C. C.} and R. Sudbrak and Borodina, {T. A.} and A. Dahl and Davydov, {A. N.} and P. Marquardt and F. Mertes and W. Nietfeld and P. Rosenstiel and S. Schreiber and Soldatov, {A. V.} and B. Timmermann and M. Tolzmann and J. Affourtit and D. Ashworth and S. Attiya and M. Bachorski and E. Buglione and A. Burke and A. Caprio and C. Celone and S. Clark and D. Conners and B. Desany and L. Gu and L. Guccione and K. Kao and A. Kebbel and J. Knowlton and M. Labrecque and L. McDade and C. Mealmaker and M. Minderman and A. Nawrocki and F. Niazi and K. Pareja and R. Ramenani and D. Riches and W. Song and C. Turcotte and S. Wang and D. Dooling and L. Fulton and R. Fulton and G. Weinstock and J. Burton and Carter, {D. M.} and C. Churcher and A. Coffey and A. Cox and A. Palotie and M. Quail and T. Skelly and J. Stalker and Swerdlow, {H. P.} and D. Turner and {De Witte}, A. and S. Giles and M. Bainbridge and D. Challis and A. Sabo and F. Yu and J. Yu and X. Fang and X. Guo and S. Tai and H. Wu and X. Zheng and Y. Zhou and Garrison, {E. P.} and W. Huang and A. Indap and Lee, {W. P.} and Leong, {W. F.} and Quinlan, {A. R.} and Ward, {A. N.} and Daly, {M. J.} and DePristo, {M. A.} and Ball, {A. D.} and E. Banks and Browning, {B. L.} and Garimella, {K. V.} and Grossman, {S. R.} and M. Hanna and C. Hartl and Kernytsky, {A. M.} and Korn, {J. M.} and H. Li and Maguire, {J. R.} and A. McKenna and Nemesh, {J. C.} and Philippakis, {A. A.} and Poplin, {R. E.} and A. Price and Rivas, {M. A.} and Sabeti, {P. C.} and Schaffner, {S. F.} and Shlyakhter, {I. A.} and Cooper, {D. N.} and Ball, {E. V.} and M. Mort and Phillips, {A. D.} and Stenson, {P. D.} and V. Makarov and Bustamante, {C. D.} and A. Boyko and J. Degenhardt and S. Gravel and Gutenkunst, {Ryan N} and M. Kaganovich and A. Keinan and P. Lacroute and X. Ma and A. Reynolds and L. Clarke and F. Cunningham and J. Herrero and S. Keenen and E. Kulesha and R. Leinonen and McLaren, {W. M.} and R. Radhakrishnan and Smith, {R. E.} and V. Zalunin and X. Zheng-Bradley and St{\"u}tz, {A. M.} and M. Bauer and T. Cox and M. Eberle and T. James and S. Kahn and L. Murray and Hyland, {F. C.} and Manning, {J. M.} and McLaughlin, {S. F.} and O. Sakarya and Sun, {Y. A.} and Tsung, {E. F.} and Albrecht, {M. W.} and Amstislavskiy, {V. S.} and R. Herwig and Parkhomchuk, {D. V.} and R. Agarwala and H. Khouri and Morgulis, {A. O.} and Paschall, {J. E.} and Phan, {L. D.} and Rotmistrovsky, {K. E.} and Sanders, {R. D.} and Shumway, {M. F.} and C. Xiao and A. Auton and G. Lunter and Marchini, {J. L.} and L. Moutsianas and S. Myers and A. Tumian and J. Knight and R. Winer and Craig, {D. W.} and Beckstrom-Sternberg, {S. M.} and A. Christoforides and Kurdoglu, {A. A.} and Pearson, {J. V.} and Sinari, {S. A.} and Tembe, {W. D.} and D. Haussler and Hinrichs, {A. S.} and Katzman, {S. J.} and A. Kern and Kuhn, {R. M.} and M. Przeworski and Hernandez, {R. D.} and B. Howie and Kelley, {J. L.} and Melton, {S. C.} and P. Anderson and T. Blackwell and W. Chen and Cookson, {W. O.} and J. Ding and Kang, {H. M.} and M. Lathrop and L. Liang and Moffatt, {M. F.} and P. Scheet and C. Sidore and X. Zhan and S. Z{\"o}llner and P. Awadalla and F. Casals and Y. Idaghdour and J. Keebler and Stone, {E. A.} and M. Zilversmit and L. Jorde and J. Xing and G. Aksay and Sahinalp, {S. C.} and Sudmant, {P. H.} and Koboldt, {D. C.} and McLellan, {M. D.} and Wallis, {J. W.} and Wendl, {M. C.} and Q. Zhang and Albers, {C. A.} and Q. Ayub and S. Balasubramaniam and Barrett, {J. C.} and Y. Chen and P. Danecek and Dermitzakis, {E. T.} and M. Hu and N. Huang and H. Jin and L. Jostins and Keane, {T. M.} and Le, {S. Q.} and S. Lindsay and Q. Long and MacArthur, {D. G.} and Montgomery, {S. B.} and L. Parts and C. Tyler-Smith and S. Balasubramanian and R. Bjornson and J. Du and L. Habegger and R. Haraksingh and J. Jee and Lam, {H. Y.} and J. Jeng and Z. Zhang and E. Bank and S. Yoon and J. Kidd and C. Coafra and H. Dinh and C. Kovar and S. Lee and L. Nazareth and J. Wilkinson and Khouri, {H. M.} and C. Scott and N. Gharani and Kaye, {J. S.} and A. Kent and T. Li and McGuire, {A. L.} and Ossorio, {P. N.} and Rotimi, {C. N.} and Y. Su and Toji, {L. H.} and Brooks, {L. D.} and Felsenfeld, {A. L.} and McEwen, {J. E.} and A. Abdallah and Juenger, {C. R.} and Clemm, {N. C.} and A. Duncanson and Green, {E. D.} and Guyer, {M. S.} and Peterson, {J. L.}",
year = "2011",
month = "2",
day = "3",
doi = "10.1038/nature09708",
language = "English (US)",
volume = "470",
pages = "59--65",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7332",

}

TY - JOUR

T1 - Mapping copy number variation by population-scale genome sequencing

AU - Mills, Ryan E.

AU - Walter, Klaudia

AU - Stewart, Chip

AU - Handsaker, Robert E.

AU - Chen, Ken

AU - Alkan, Can

AU - Abyzov, Alexej

AU - Yoon, Seungtai Chris

AU - Ye, Kai

AU - Cheetham, R. Keira

AU - Chinwalla, Asif

AU - Conrad, Donald F.

AU - Fu, Yutao

AU - Grubert, Fabian

AU - Hajirasouliha, Iman

AU - Hormozdiari, Fereydoun

AU - Iakoucheva, Lilia M.

AU - Iqbal, Zamin

AU - Kang, Shuli

AU - Kidd, Jeffrey M.

AU - Konkel, Miriam K.

AU - Korn, Joshua

AU - Khurana, Ekta

AU - Kural, Deniz

AU - Lam, Hugo Y.K.

AU - Leng, Jing

AU - Li, Ruiqiang

AU - Li, Yingrui

AU - Lin, Chang Yun

AU - Luo, Ruibang

AU - Mu, Xinmeng Jasmine

AU - Nemesh, James

AU - Peckham, Heather E.

AU - Rausch, Tobias

AU - Scally, Aylwyn

AU - Shi, Xinghua

AU - Stromberg, Michael P.

AU - Sütz, Adrian M.

AU - Urban, Alexander Eckehart

AU - Walker, Jerilyn A.

AU - Wu, Jiantao

AU - Zhang, Yujun

AU - Zhang, Zhengdong D.

AU - Batzer, Mark A.

AU - Ding, Li

AU - Marth, Gabor T.

AU - McVean, Gil

AU - Sebat, Jonathan

AU - Snyder, Michael

AU - Wang, Jun

AU - Ye, Kenny

AU - Eichler, Evan E.

AU - Gerstein, Mark B.

AU - Hurles, Matthew E.

AU - Lee, Charles

AU - McCarroll, Steven A.

AU - Korbel, Jan O.

AU - Collins, Francis S.

AU - Altshuler, D. L.

AU - Durbin, R. M.

AU - Abecasis, G. R.

AU - Bentley, D. R.

AU - Chakravarti, A.

AU - Clark, A. G.

AU - De La Vega, F. M.

AU - Donnelly, P.

AU - Egholm, M.

AU - Flicek, P.

AU - Gabriel, S. B.

AU - Gibbs, R. A.

AU - Knoppers, B. M.

AU - Lander, E. S.

AU - Lehrach, H.

AU - Mardis, E. R.

AU - McVean, G. A.

AU - Nickerson, D. A.

AU - Peltonen, L.

AU - Schafer, A. J.

AU - Sherry, S. T.

AU - Wilson, R. K.

AU - Deiros, D.

AU - Metzker, M.

AU - Muzny, D.

AU - Reid, J.

AU - Wheeler, D.

AU - Li, J.

AU - Jian, M.

AU - Li, G.

AU - Liang, H.

AU - Tian, G.

AU - Wang, B.

AU - Wang, W.

AU - Yang, H.

AU - Zhang, X.

AU - Zheng, H.

AU - Ambrogio, L.

AU - Bloom, T.

AU - Cibulskis, K.

AU - Fennell, T. J.

AU - Jaffe, D. B.

AU - Shefler, E.

AU - Sougnez, C. L.

AU - Gormley, N.

AU - Humphray, S.

AU - Kingsbury, Z.

AU - Koko-Gonzales, P.

AU - Stone, J.

AU - McKernan, K. J.

AU - Costa, G. L.

AU - Ichikawa, J. K.

AU - Lee, C. C.

AU - Sudbrak, R.

AU - Borodina, T. A.

AU - Dahl, A.

AU - Davydov, A. N.

AU - Marquardt, P.

AU - Mertes, F.

AU - Nietfeld, W.

AU - Rosenstiel, P.

AU - Schreiber, S.

AU - Soldatov, A. V.

AU - Timmermann, B.

AU - Tolzmann, M.

AU - Affourtit, J.

AU - Ashworth, D.

AU - Attiya, S.

AU - Bachorski, M.

AU - Buglione, E.

AU - Burke, A.

AU - Caprio, A.

AU - Celone, C.

AU - Clark, S.

AU - Conners, D.

AU - Desany, B.

AU - Gu, L.

AU - Guccione, L.

AU - Kao, K.

AU - Kebbel, A.

AU - Knowlton, J.

AU - Labrecque, M.

AU - McDade, L.

AU - Mealmaker, C.

AU - Minderman, M.

AU - Nawrocki, A.

AU - Niazi, F.

AU - Pareja, K.

AU - Ramenani, R.

AU - Riches, D.

AU - Song, W.

AU - Turcotte, C.

AU - Wang, S.

AU - Dooling, D.

AU - Fulton, L.

AU - Fulton, R.

AU - Weinstock, G.

AU - Burton, J.

AU - Carter, D. M.

AU - Churcher, C.

AU - Coffey, A.

AU - Cox, A.

AU - Palotie, A.

AU - Quail, M.

AU - Skelly, T.

AU - Stalker, J.

AU - Swerdlow, H. P.

AU - Turner, D.

AU - De Witte, A.

AU - Giles, S.

AU - Bainbridge, M.

AU - Challis, D.

AU - Sabo, A.

AU - Yu, F.

AU - Yu, J.

AU - Fang, X.

AU - Guo, X.

AU - Tai, S.

AU - Wu, H.

AU - Zheng, X.

AU - Zhou, Y.

AU - Garrison, E. P.

AU - Huang, W.

AU - Indap, A.

AU - Lee, W. P.

AU - Leong, W. F.

AU - Quinlan, A. R.

AU - Ward, A. N.

AU - Daly, M. J.

AU - DePristo, M. A.

AU - Ball, A. D.

AU - Banks, E.

AU - Browning, B. L.

AU - Garimella, K. V.

AU - Grossman, S. R.

AU - Hanna, M.

AU - Hartl, C.

AU - Kernytsky, A. M.

AU - Korn, J. M.

AU - Li, H.

AU - Maguire, J. R.

AU - McKenna, A.

AU - Nemesh, J. C.

AU - Philippakis, A. A.

AU - Poplin, R. E.

AU - Price, A.

AU - Rivas, M. A.

AU - Sabeti, P. C.

AU - Schaffner, S. F.

AU - Shlyakhter, I. A.

AU - Cooper, D. N.

AU - Ball, E. V.

AU - Mort, M.

AU - Phillips, A. D.

AU - Stenson, P. D.

AU - Makarov, V.

AU - Bustamante, C. D.

AU - Boyko, A.

AU - Degenhardt, J.

AU - Gravel, S.

AU - Gutenkunst, Ryan N

AU - Kaganovich, M.

AU - Keinan, A.

AU - Lacroute, P.

AU - Ma, X.

AU - Reynolds, A.

AU - Clarke, L.

AU - Cunningham, F.

AU - Herrero, J.

AU - Keenen, S.

AU - Kulesha, E.

AU - Leinonen, R.

AU - McLaren, W. M.

AU - Radhakrishnan, R.

AU - Smith, R. E.

AU - Zalunin, V.

AU - Zheng-Bradley, X.

AU - Stütz, A. M.

AU - Bauer, M.

AU - Cox, T.

AU - Eberle, M.

AU - James, T.

AU - Kahn, S.

AU - Murray, L.

AU - Hyland, F. C.

AU - Manning, J. M.

AU - McLaughlin, S. F.

AU - Sakarya, O.

AU - Sun, Y. A.

AU - Tsung, E. F.

AU - Albrecht, M. W.

AU - Amstislavskiy, V. S.

AU - Herwig, R.

AU - Parkhomchuk, D. V.

AU - Agarwala, R.

AU - Khouri, H.

AU - Morgulis, A. O.

AU - Paschall, J. E.

AU - Phan, L. D.

AU - Rotmistrovsky, K. E.

AU - Sanders, R. D.

AU - Shumway, M. F.

AU - Xiao, C.

AU - Auton, A.

AU - Lunter, G.

AU - Marchini, J. L.

AU - Moutsianas, L.

AU - Myers, S.

AU - Tumian, A.

AU - Knight, J.

AU - Winer, R.

AU - Craig, D. W.

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PY - 2011/2/3

Y1 - 2011/2/3

N2 - Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.

AB - Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.

UR - http://www.scopus.com/inward/record.url?scp=84975804424&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975804424&partnerID=8YFLogxK

U2 - 10.1038/nature09708

DO - 10.1038/nature09708

M3 - Article

VL - 470

SP - 59

EP - 65

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7332

ER -