By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.
An integrated map of genetic variation from 1,092 human genomes / Altshuler, Dm; Durbin, Rm; Abecasis, Gr; Bentley, Dr; Chakravarti, A; Clark, Ag; Donnelly, P; Eichler, Ee; Flicek, P; Gabriel, Sb; Gibbs, Ra; Green, Ed; Hurles, Me; Knoppers, Bm; Korbel, Jo; Lander, Es; Lee, C; Lehrach, H; Mardis, Er; Marth, Gt; Mcvean, Ga; Nickerson, Da; Schmidt, Jp; Sherry, St; Wang, J; Wilson, Rk; Gibbs, Ra; Dinh, H; Kovar, C; Lee, S; Lewis, L; Muzny, D; Reid, J; Wang, M; Wang, J; Fang, Xd; Guo, Xs; Jian, M; Jiang, H; Jin, X; Li, Gq; Li, Jx; Li, Yr; Li, Z; Liu, X; Lu, Y; Ma, Xd; Su, Z; Tai, Ss; Tang, Mf; Wang, B; Wang, Gb; Wu, Hl; Wu, Rh; Yin, Y; Zhang, Ww; Zhao, J; Zhao, Mr; Zheng, Xl; Zhou, Y; Lander, Es; Altshuler, Dm; Gabriel, Sb; Gupta, N; Flicek, P; Clarke, L; Leinonen, R; Smith, Re; Zheng Bradley, X; Bentley, Dr; Grocock, R; Humphray, S; James, T; Kingsbury, Z; Lehrach, H; Sudbrak, R; Albrecht, Mw; Amstislavskiy, Vs; Borodina, Ta; Lienhard, M; Mertes, F; Sultan, M; Timmermann, B; Yaspo, Ml; Sherry, St; Mcvean, Ga; Mardis, Er; Wilson, Rk; Fulton, L; Fulton, R; Weinstock, Gm; Durbin, Rm; Balasubramaniam, S; Burton, J; Danecek, P; Keane, Tm; Kolb Kokocinski, A; Mccarthy, S; Stalker, J; Quail, M; Schmidt, Jp; Davies, Cj; Gollub, J; Webster, T; Wong, B; Zhan, Yp; Auton, A; Gibbs, Ra; Yu, F; Bainbridge, M; Challis, D; Evani, Us; Lu, J; Muzny, D; Nagaswamy, U; Reid, J; Sabo, A; Wang, Y; Yu, J; Wang, J; Coin, Ljm; Fang, L; Guo, Xs; Jin, X; Li, Gq; Li, Qb; Li, Yr; Li, Zy; Lin, Hx; Liu, Bh; Luo, Rb; Qin, N; Shao, Hj; Wang, Bq; Xie, Yl; Ye, C; Yu, C; Zhang, F; Zheng, Hc; Zhu, Hm; Marth, Gt; Garrison, Ep; Kural, D; Lee, Wp; Leong, Wf; Ward, An; Wu, Jt; Zhang, My; Lee, C; Griffin, L; Hsieh, Ch; Mills, Re; Shi, Xh; von Grotthuss, M; Zhang, Cs; Daly, Mj; Depristo, Ma; Altshuler, Dm; Banks, E; Bhatia, G; Carneiro, Mo; del Angel, G; Gabriel, Sb; Genovese, G; Gupta, N; Handsaker, Re; Hartl, C; Lander, Es; Mccarroll, Sa; Nemesh, Jc; Poplin, Re; Schaffner, Sf; Shakir, K; Yoon, Sc; Lihm, J; Makarov, V; Jin, Hj; Kim, W; Kim, Kc; Korbel, Jo; Rausch, T; Flicek, P; Beal, K; Clarke, L; Cunningham, F; Herrero, J; Mclaren, Wm; Ritchie, Grs; Smith, Re; Zheng Bradley, X; Clark, Ag; Gottipati, S; Keinan, A; Rodriguez Flores, Jl; Sabeti, Pc; Grossman, Sr; Tabrizi, S; Tariyal, R; Cooper, Dn; Ball, Ev; Stenson, Pd; Bentley, Dr; Barnes, B; Bauer, M; Cheetham, Rk; Cox, T; Eberle, M; Humphray, S; Kahn, S; Murray, L; Peden, J; Shaw, R; Ye, K; Batzer, Ma; Konkel, Mk; Walker, Ja; Macarthur, Dg; Lek, M; Sudbrak, R; Amstislavskiy, Vs; Herwig, R; Shriver, Md; Bustamante, Cd; Byrnes, Jk; De la Vega, Fm; Gravel, S; Kenny, Ee; Kidd, Jm; Lacroute, P; Maples, Bk; Moreno Estrada, A; Zakharia, F; Halperin, E; Baran, Y; Craig, Dw; Christoforides, A; Homer, N; Izatt, T; Kurdoglu, Aa; Sinari, Sa; Squire, K; Sherry, St; Xiao, Cl; Sebat, J; Bafna, V; Ye, K; Burchard, Eg; Hernandez, Rd; Gignoux, Cr; Haussler, D; Katzman, Sj; Kent, Wj; Howie, B; Ruiz Linares, A; Dermitzakis, Et; Lappalainen, T; Devine, Se; Liu, Xy; Maroo, A; Tallon, Lj; Rosenfeld, Ja; Michelson, Lp; Abecasis, Gr; Kang, Hm; Anderson, P; Angius, A; Bigham, A; Blackwell, T; Busonero, F; Cucca, Francesco; Fuchsberger, C; Jones, C; Jun, G; Li, Y; Lyons, R; Maschio, A; Porcu, E; Reinier, F; Sanna, S; Schlessinger, D; Sidore, C; Tan, A; Trost, Mk; Awadalla, P; Hodgkinson, A; Lunter, G; Mcvean, Ga; Marchini, Jl; Myers, S; Churchhouse, C; Delaneau, O; Gupta Hinch, A; Iqbal, Z; Mathieson, I; Rimmer, A; Xifara, Dk; Oleksyk, Tk; Fu, Yx; Liu, Xm; Xiong, Mm; Jorde, L; Witherspoon, D; Xing, Jc; Eichler, Ee; Browning, Bl; Alkan, C; Hajirasouliha, I; Hormozdiari, F; Ko, A; Sudmant, Ph; Mardis, Er; Chen, K; Chinwalla, A; Ding, L; Dooling, D; Koboldt, Dc; Mclellan, Md; Wallis, Jw; Wendl, Mc; Zhang, Qy; Durbin, Rm; Hurles, Me; Tyler Smith, C; Albers, Ca; Ayub, Q; Balasubramaniam, S; Chen, Y; Coffey, Aj; Colonna, V; Danecek, P; Huang, N; Jostins, L; Keane, Tm; Li, H; Mccarthy, S; Scally, A; Stalker, J; Walter, K; Xue, Yl; Zhang, Yj; Gerstein, Mb; Abyzov, A; Balasubramanian, S; Chen, Jm; Clarke, D; Fu, Y; Habegger, L; Harmanci, Ao; Jin, Mk; Khurana, E; Mu, Xj; Sisu, C; Li, Yr; Luo, Rb; Zhu, Hm; Lee, C; Griffin, L; Hsieh, Ch; Mills, Re; Shi, Xh; von Grotthuss, M; Zhang, Cs; Marth, Gt; Garrison, Ep; Kural, D; Lee, Wp; Ward, An; Wu, Jt; Zhang, My; Mccarroll, Sa; Altshuler, Dm; Banks, E; del Angel, G; Genovese, G; Handsaker, Re; Hartl, C; Nemesh, Jc; Shakir, K; Yoon, Sc; Lihm, J; Makarov, V; Degenhardt, J; Flicek, P; Clarke, L; Smith, Re; Zheng Bradley, X; Korbel, Jo; Rausch, T; Stutz, Am; Bentley, Dr; Barnes, B; Cheetham, Rk; Eberle, M; Humphray, S; Kahn, S; Murray, L; Shaw, R; Ye, K; Batzer, Ma; Konkel, Mk; Walker, Ja; Lacroute, P; Craig, Dw; Homer, N; Church, D; Xiao, Cl; Sebat, J; Bafna, V; Michaelson, Jj; Ye, K; Devine, Se; Liu, Xy; Maroo, A; Tallon, Lj; Lunter, G; Mcvean, Ga; Iqbal, Z; Witherspoon, D; Xing, Jc; Eichler, Ee; Alkan, C; Hajirasouliha, I; Hormozdiari, F; Ko, A; Sudmant, Ph; Chen, K; Chinwalla, A; Ding, L; Mclellan, Md; Wallis, Jw; Hurles, Me; Ben, Blackburne; Li, H; Lindsay, Sj; Ning, Zm; Scally, A; Walter, K; Zhang, Yj; Gerstein, Mb; Abyzov, A; Chen, Jm; Clarke, D; Khurana, E; Mu, Xj; Sisu, C; Gibbs, Ra; Yu, Fl; Bainbridge, M; Challis, D; Evani, Us; Kovar, C; Lewis, L; Lu, J; Muzny, D; Nagaswamy, U; Reid, J; Sabo, A; Yu, J; Guo, Xs; Li, Yr; Wu, Rh; Marth, Gt; Garrison, Ep; Leong, Wf; Ward, An; del Angel, G; Depristo, Ma; Gabriel, Sb; Gupta, N; Hartl, C; Poplin, Re; Clark, Ag; Rodriguez Flores, Jl; Flicek, P; Clarke, L; Smith, Re; Zheng Bradley, X; Macarthur, Dg; Bustamante, Cd; Gravel, S; Craig, Dw; Christoforides, A; Homer, N; Izatt, T; Sherry, St; Xiao, Cl; Dermitzakis, Et; Abecasis, Gr; Kang, Hm; Mcvean, Ga; Mardis, Er; Dooling, D; Fulton, L; Fulton, R; Koboldt, Dc; Durbin, Rm; Balasubramaniam, S; Keane, Tm; Mccarthy, S; Stalker, J; Gerstein, Mb; Balasubramanian, S; Habegger, L; Garrison, Ep; Gibbs, Ra; Bainbridge, M; Muzny, D; Yu, Fl; Yu, J; del Angel, G; Handsaker, Re; Makarov, V; Rodriguez Flores, Jl; Jin, Hj; Kim, W; Kim, Kc; Flicek, P; Beal, K; Clarke, L; Cunningham, F; Herrero, J; Mclaren, Wm; Ritchie, Grs; Zheng Bradley, X; Tabrizi, S; Macarthur, Dg; Lek, M; Bustamante, Cd; De la Vega, Fm; Craig, Dw; Kurdoglu, Aa; Lappalainen, T; Rosenfeld, Ja; Michelson, Lp; Awadalla, P; Hodgkinson, A; Mcvean, Ga; Chen, K; Tyler Smith, C; Chen, Y; Colonna, V; Frankish, A; Harrow, J; Xue, Yl; Gerstein, Mb; Abyzov, A; Balasubramanian, S; Chen, Jm; Clarke, D; Fu, Y; Harmanci, Ao; Jin, Mk; Khurana, E; Mu, Xj; Sisu, C; Gibbs, Ra; Fowler, G; Hale, W; Kalra, D; Kovar, C; Muzny, D; Reid, J; Wang, J; Guo, X; Li, G; Li, Y; Zheng, X; Altshuler, Dm; Flicek, P; Clarke, L; Barker, J; Kelman, G; Kulesha, E; Leinonen, R; Mclaren, Wm; Radhakrishnan, R; Roa, A; Smirnov, D; Smith, Re; Streeter, I; Toneva, I; Vaughan, B; Zheng Bradley, X; Bentley, Dr; Cox, T; Humphray, S; Kahn, S; Sudbrak, R; Albrecht, Mw; Lienhard, M; Craig, Dw; Izatt, T; Kurdoglu, Aa; Sherry, St; Ananiev, V; Belaia, Z; Beloslyudtsev, D; Bouk, N; Chen, C; Church, D; Cohen, R; Cook, C; Garner, J; Hefferon, T; Kimelman, M; Liu, C; Lopez, J; Meric, P; O'Sullivan, C; Ostapchuk, Y; Phan, L; Ponomarov, S; Schneider, V; Shekhtman, E; Sirotkin, K; Slotta, D; Xiao, Cl; Zhang, H; Haussler, D; Abecasis, Gr; Mcvean, Ga; Alkan, C; Ko, A; Dooling, D; Durbin, Rm; Balasubramaniam, S; Keane, Tm; Mccarthy, S; Stalker, J; Chakravarti, A; Knoppers, Bm; Abecasis, Gr; Barnes, Kc; Beiswanger, C; Burchard, Eg; Bustamante, Cd; Cai, Hy; Cao, Hz; Durbin, Rm; Gharani, N; Gibbs, Ra; Gignoux, Cr; Gravel, S; Henn, B; Jones, D; Jorde, L; Kaye, Js; Keinan, A; Kent, A; Kerasidou, A; Li, Yr; Mathias, R; Mcvean, Ga; Moreno Estrada, A; Ossorio, Pn; Parker, M; Reich, D; Rotimi, Cn; Royal, Cd; Sandoval, K; Su, Yy; Sudbrak, R; Tian, Zm; Timmermann, B; Tishkoff, S; Toji, Lh; Tyler Smith, C; Via, M; Wang, Yh; Yang, Hm; Yang, L; Zhu, Jy; Bodmer, W; Bedoya, G; Ruiz Linares, A; Ming, Cz; Yang, G; You, Cj; Peltonen, L; Garcia Montero, A; Orfao, A; Dutil, J; Martinez Cruzado, Jc; Oleksyk, Tk; Brooks, Ld; Felsenfeld, Al; Mcewen, Je; Clemm, Nc; Duncanson, A; Dunn, M; Green, Ed; Guyer, Ms; Peterson, Jl; Abecasis, Gr; Auton, A; Brooks, Ld; Depristo, Ma; Durbin, Rm; Handsaker, Re; Kang, Hm; Marth, Gt; Mcvean, Ga. - In: NATURE. - ISSN 0028-0836. - 491:7422(2012), pp. 56-65. [10.1038/nature11632]
An integrated map of genetic variation from 1,092 human genomes
Altshuler DM; Durbin RM; Abecasis GR; Bentley DR; Chakravarti A; Clark AG; Donnelly P; Eichler EE; Flicek P; Gabriel SB; Gibbs RA; Green ED; Hurles ME; Knoppers BM; Korbel JO; Lander ES; Lee C; Lehrach H; Mardis ER; Marth GT; McVean GA; Nickerson DA; Schmidt JP; Sherry ST; Wang J; Wilson RK; Gibbs RA; Dinh H; Kovar C; Lee S; Lewis L; Muzny D; Reid J; Wang M; Wang J; Fang XD; Guo XS; Jian M; Jiang H; Jin X; Li GQ; Li JX; Li YR; Li Z; Liu X; Lu Y; Ma XD; Su Z; Tai SS; Tang MF; Wang B; Wang GB; Wu HL; Wu RH; Yin Y; Zhang WW; Zhao J; Zhao MR; Zheng XL; Zhou Y; Lander ES; Altshuler DM; Gabriel SB; Gupta N; Flicek P; Clarke L; Leinonen R; Smith RE; Zheng Bradley X; Bentley DR; Grocock R; Humphray S; James T; Kingsbury Z; Lehrach H; Sudbrak R; Albrecht MW; Amstislavskiy VS; Borodina TA; Lienhard M; Mertes F; Sultan M; Timmermann B; Yaspo ML; Sherry ST; McVean GA; Mardis ER; Wilson RK; Fulton L; Fulton R; Weinstock GM; Durbin RM; Balasubramaniam S; Burton J; Danecek P; Keane TM; Kolb Kokocinski A; McCarthy S; Stalker J; Quail M; Schmidt JP; Davies CJ; Gollub J; Webster T; Wong B; Zhan YP; Auton A; Gibbs RA; Yu F; Bainbridge M; Challis D; Evani US; Lu J; Muzny D; Nagaswamy U; Reid J; Sabo A; Wang Y; Yu J; Wang J; Coin LJM; Fang L; Guo XS; Jin X; Li GQ; Li QB; Li YR; Li ZY; Lin HX; Liu BH; Luo RB; Qin N; Shao HJ; Wang BQ; Xie YL; Ye C; Yu C; Zhang F; Zheng HC; Zhu HM; Marth GT; Garrison EP; Kural D; Lee WP; Leong WF; Ward AN; Wu JT; Zhang MY; Lee C; Griffin L; Hsieh CH; Mills RE; Shi XH; von Grotthuss M; Zhang CS; Daly MJ; DePristo MA; Altshuler DM; Banks E; Bhatia G; Carneiro MO; del Angel G; Gabriel SB; Genovese G; Gupta N; Handsaker RE; Hartl C; Lander ES; McCarroll SA; Nemesh JC; Poplin RE; Schaffner SF; Shakir K; Yoon SC; Lihm J; Makarov V; Jin HJ; Kim W; Kim KC; Korbel JO; Rausch T; Flicek P; Beal K; Clarke L; Cunningham F; Herrero J; McLaren WM; Ritchie GRS; Smith RE; Zheng Bradley X; Clark AG; Gottipati S; Keinan A; Rodriguez Flores JL; Sabeti PC; Grossman SR; Tabrizi S; Tariyal R; Cooper DN; Ball EV; Stenson PD; Bentley DR; Barnes B; Bauer M; Cheetham RK; Cox T; Eberle M; Humphray S; Kahn S; Murray L; Peden J; Shaw R; Ye K; Batzer MA; Konkel MK; Walker JA; MacArthur DG; Lek M; Sudbrak R; Amstislavskiy VS; Herwig R; Shriver MD; Bustamante CD; Byrnes JK; De la Vega FM; Gravel S; Kenny EE; Kidd JM; Lacroute P; Maples BK; Moreno Estrada A; Zakharia F; Halperin E; Baran Y; Craig DW; Christoforides A; Homer N; Izatt T; Kurdoglu AA; Sinari SA; Squire K; Sherry ST; Xiao CL; Sebat J; Bafna V; Ye K; Burchard EG; Hernandez RD; Gignoux CR; Haussler D; Katzman SJ; Kent WJ; Howie B; Ruiz Linares A; Dermitzakis ET; Lappalainen T; Devine SE; Liu XY; Maroo A; Tallon LJ; Rosenfeld JA; Michelson LP; Abecasis GR; Kang HM; Anderson P; Angius A; Bigham A; Blackwell T; Busonero F; CUCCA, Francesco ;Fuchsberger C; Jones C; Jun G; Li Y; Lyons R; Maschio A; Porcu E; Reinier F; Sanna S; Schlessinger D; Sidore C; Tan A; Trost MK; Awadalla P; Hodgkinson A; Lunter G; McVean GA; Marchini JL; Myers S; Churchhouse C; Delaneau O; Gupta Hinch A; Iqbal Z; Mathieson I; Rimmer A; Xifara DK; Oleksyk TK; Fu YX; Liu XM; Xiong MM; Jorde L; Witherspoon D; Xing JC; Eichler EE; Browning BL; Alkan C; Hajirasouliha I; Hormozdiari F; Ko A; Sudmant PH; Mardis ER; Chen K; Chinwalla A; Ding L; Dooling D; Koboldt DC; McLellan MD; Wallis JW; Wendl MC; Zhang QY; Durbin RM; Hurles ME; Tyler Smith C; Albers CA; Ayub Q; Balasubramaniam S; Chen Y; Coffey AJ; Colonna V; Danecek P; Huang N; Jostins L; Keane TM; Li H; McCarthy S; Scally A; Stalker J; Walter K; Xue YL; Zhang YJ; Gerstein MB; Abyzov A; Balasubramanian S; Chen JM; Clarke D; Fu Y; Habegger L; Harmanci AO; Jin MK; Khurana E; Mu XJ; Sisu C; Li YR; Luo RB; Zhu HM; Lee C; Griffin L; Hsieh CH; Mills RE; Shi XH; von Grotthuss M; Zhang CS; Marth GT; Garrison EP; Kural D; Lee WP; Ward AN; Wu JT; Zhang MY; McCarroll SA; Altshuler DM; Banks E; del Angel G; Genovese G; Handsaker RE; Hartl C; Nemesh JC; Shakir K; Yoon SC; Lihm J; Makarov V; Degenhardt J; Flicek P; Clarke L; Smith RE; Zheng Bradley X; Korbel JO; Rausch T; Stutz AM; Bentley DR; Barnes B; Cheetham RK; Eberle M; Humphray S; Kahn S; Murray L; Shaw R; Ye K; Batzer MA; Konkel MK; Walker JA; Lacroute P; Craig DW; Homer N; Church D; Xiao CL; Sebat J; Bafna V; Michaelson JJ; Ye K; Devine SE; Liu XY; Maroo A; Tallon LJ; Lunter G; McVean GA; Iqbal Z; Witherspoon D; Xing JC; Eichler EE; Alkan C; Hajirasouliha I; Hormozdiari F; Ko A; Sudmant PH; Chen K; Chinwalla A; Ding L; McLellan MD; Wallis JW; Hurles ME; Ben Blackburne; Li H; Lindsay SJ; Ning ZM; Scally A; Walter K; Zhang YJ; Gerstein MB; Abyzov A; Chen JM; Clarke D; Khurana E; Mu XJ; Sisu C; Gibbs RA; Yu FL; Bainbridge M; Challis D; Evani US; Kovar C; Lewis L; Lu J; Muzny D; Nagaswamy U; Reid J; Sabo A; Yu J; Guo XS; Li YR; Wu RH; Marth GT; Garrison EP; Leong WF; Ward AN; del Angel G; DePristo MA; Gabriel SB; Gupta N; Hartl C; Poplin RE; Clark AG; Rodriguez Flores JL; Flicek P; Clarke L; Smith RE; Zheng Bradley X; MacArthur DG; Bustamante CD; Gravel S; Craig DW; Christoforides A; Homer N; Izatt T; Sherry ST; Xiao CL; Dermitzakis ET; Abecasis GR; Kang HM; McVean GA; Mardis ER; Dooling D; Fulton L; Fulton R; Koboldt DC; Durbin RM; Balasubramaniam S; Keane TM; McCarthy S; Stalker J; Gerstein MB; Balasubramanian S; Habegger L; Garrison EP; Gibbs RA; Bainbridge M; Muzny D; Yu FL; Yu J; del Angel G; Handsaker RE; Makarov V; Rodriguez Flores JL; Jin HJ; Kim W; Kim KC; Flicek P; Beal K; Clarke L; Cunningham F; Herrero J; McLaren WM; Ritchie GRS; Zheng Bradley X; Tabrizi S; MacArthur DG; Lek M; Bustamante CD; De la Vega FM; Craig DW; Kurdoglu AA; Lappalainen T; Rosenfeld JA; Michelson LP; Awadalla P; Hodgkinson A; McVean GA; Chen K; Tyler Smith C; Chen Y; Colonna V; Frankish A; Harrow J; Xue YL; Gerstein MB; Abyzov A; Balasubramanian S; Chen JM; Clarke D; Fu Y; Harmanci AO; Jin MK; Khurana E; Mu XJ; Sisu C; Gibbs RA; Fowler G; Hale W; Kalra D; Kovar C; Muzny D; Reid J; Wang J; Guo X; Li G; Li Y; Zheng X; Altshuler DM; Flicek P; Clarke L; Barker J; Kelman G; Kulesha E; Leinonen R; McLaren WM; Radhakrishnan R; Roa A; Smirnov D; Smith RE; Streeter I; Toneva I; Vaughan B; Zheng Bradley X; Bentley DR; Cox T; Humphray S; Kahn S; Sudbrak R; Albrecht MW; Lienhard M; Craig DW; Izatt T; Kurdoglu AA; Sherry ST; Ananiev V; Belaia Z; Beloslyudtsev D; Bouk N; Chen C; Church D; Cohen R; Cook C; Garner J; Hefferon T; Kimelman M; Liu C; Lopez J; Meric P; O'Sullivan C; Ostapchuk Y; Phan L; Ponomarov S; Schneider V; Shekhtman E; Sirotkin K; Slotta D; Xiao CL; Zhang H; Haussler D; Abecasis GR; McVean GA; Alkan C; Ko A; Dooling D; Durbin RM; Balasubramaniam S; Keane TM; McCarthy S; Stalker J; Chakravarti A; Knoppers BM; Abecasis GR; Barnes KC; Beiswanger C; Burchard EG; Bustamante CD; Cai HY; Cao HZ; Durbin RM; Gharani N; Gibbs RA; Gignoux CR; Gravel S; Henn B; Jones D; Jorde L; Kaye JS; Keinan A; Kent A; Kerasidou A; Li YR; Mathias R; McVean GA; Moreno Estrada A; Ossorio PN; Parker M; Reich D; Rotimi CN; Royal CD; Sandoval K; Su YY; Sudbrak R; Tian ZM; Timmermann B; Tishkoff S; Toji LH; Tyler Smith C; Via M; Wang YH; Yang HM; Yang L; Zhu JY; Bodmer W; Bedoya G; Ruiz Linares A; Ming CZ; Yang G; You CJ; Peltonen L; Garcia Montero A; Orfao A; Dutil J; Martinez Cruzado JC; Oleksyk TK; Brooks LD; Felsenfeld AL; McEwen JE; Clemm NC; Duncanson A; Dunn M; Green ED; Guyer MS; Peterson JL; Abecasis GR; Auton A; Brooks LD; DePristo MA; Durbin RM; Handsaker RE; Kang HM; Marth GT; McVean GA
2012-01-01
Abstract
By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.
Citazione
An integrated map of genetic variation from 1,092 human genomes / Altshuler, Dm; Durbin, Rm; Abecasis, Gr; Bentley, Dr; Chakravarti, A; Clark, Ag; Donnelly, P; Eichler, Ee; Flicek, P; Gabriel, Sb; Gibbs, Ra; Green, Ed; Hurles, Me; Knoppers, Bm; Korbel, Jo; Lander, Es; Lee, C; Lehrach, H; Mardis, Er; Marth, Gt; Mcvean, Ga; Nickerson, Da; Schmidt, Jp; Sherry, St; Wang, J; Wilson, Rk; Gibbs, Ra; Dinh, H; Kovar, C; Lee, S; Lewis, L; Muzny, D; Reid, J; Wang, M; Wang, J; Fang, Xd; Guo, Xs; Jian, M; Jiang, H; Jin, X; Li, Gq; Li, Jx; Li, Yr; Li, Z; Liu, X; Lu, Y; Ma, Xd; Su, Z; Tai, Ss; Tang, Mf; Wang, B; Wang, Gb; Wu, Hl; Wu, Rh; Yin, Y; Zhang, Ww; Zhao, J; Zhao, Mr; Zheng, Xl; Zhou, Y; Lander, Es; Altshuler, Dm; Gabriel, Sb; Gupta, N; Flicek, P; Clarke, L; Leinonen, R; Smith, Re; Zheng Bradley, X; Bentley, Dr; Grocock, R; Humphray, S; James, T; Kingsbury, Z; Lehrach, H; Sudbrak, R; Albrecht, Mw; Amstislavskiy, Vs; Borodina, Ta; Lienhard, M; Mertes, F; Sultan, M; Timmermann, B; Yaspo, Ml; Sherry, St; 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[10.1038/nature11632]
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Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande. La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.