Browsing by Subject "Genetics, Population"

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Open Access
CONGA: Copy number variation genotyping in ancient genomes and low-coverage sequencing data
(Public Library of Science, 2022-12-14) Söylev, Arda; Çokoglu, Sevim Seda; Koptekin, Dilek; Alkan, Can; Somel, Mehmet
To date, ancient genome analyses have been largely confined to the study of single nucleotide polymorphisms (SNPs). Copy number variants (CNVs) are a major contributor of disease and of evolutionary adaptation, but identifying CNVs in ancient shotgun-sequenced genomes is hampered by typical low genome coverage (<1×) and short fragments ([removed]1 kbps with F-scores >0.75 at ≥1×, and distinguish between heterozygous and homozygous states. We used CONGA to genotype 10,002 outgroup-ascertained deletions across a heterogenous set of 71 ancient human genomes spanning the last 50,000 years, produced using variable experimental protocols. A fraction of these (21/71) display divergent deletion profiles unrelated to their population origin, but attributable to technical factors such as coverage and read length. The majority of the sample (50/71), despite originating from nine different laboratories and having coverages ranging from 0.44×-26× (median 4×) and average read lengths 52-121 bps (median 69), exhibit coherent deletion frequencies. Across these 50 genomes, inter-individual genetic diversity measured using SNPs and CONGA-genotyped deletions are highly correlated. CONGA-genotyped deletions also display purifying selection signatures, as expected. CONGA thus paves the way for systematic CNV analyses in ancient genomes, despite the technical challenges posed by low and variable genome coverage. © 2022 Söylev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Open Access
An integrated map of genetic variation from 1,092 human genomes
(Nature Publishing Group, 2012) Altshuler, D.M.; Durbin, R.M.; Abecasis G.R.; Bentley, D.R.; Chakravarti, A.; Clark, A.G.; Donnelly P.; Eichler, E.E.; Flicek P.; Gabriel, S.B.; Gibbs, R.A.; Green, E.D.; Hurles, M.E.; Knoppers, B.M.; Korbel J.O.; Lander, E.S.; Lee, C.; Lehrach H.; Mardis, E.R.; Marth G.T.; McVean G.A.; Nickerson, D.A.; Schmidt J.P.; Sherry, S.T.; Wang, J.; Wilson, R.K.; Dinh H.; Kovar, C.; Lee, S.; Lewis L.; Muzny, D.; Reid J.; Wang, M.; Fang X.; Guo X.; Jian, M.; Jiang H.; Jin X.; Li G.; Li J.; Li Y.; Li, Z.; Liu X.; Lu, Y.; Ma X.; Su, Z.; Tai, S.; Tang, M.; Wang, B.; Wang G.; Wu H.; Wu, R.; Yin, Y.; Zhang W.; Zhao J.; Zhao, M.; Zheng X.; Zhou, Y.; Gupta, N.; Clarke L.; Leinonen, R.; Smith, R.E.; Zheng-Bradley X.; Grocock, R.; Humphray, S.; James, T.; Kingsbury, Z.; Sudbrak, R.; Albrecht, M.W.; Amstislavskiy V.S.; Borodina, T.A.; Lienhard, M.; Mertes F.; Sultan, M.; Timmermann, B.; Yaspo, M.-L.; Fulton L.; Fulton, R.; Weinstock G.M.; Balasubramaniam, S.; Burton J.; Danecek P.; Keane, T.M.; Kolb-Kokocinski, A.; McCarthy, S.; Stalker J.; Quail, M.; Davies, C.J.; Gollub J.; Webster, T.; Wong, B.; Zhan, Y.; Auton, A.; Yu F.; Bainbridge, M.; Challis, D.; Evani, U.S.; Lu J.; Nagaswamy, U.; Sabo, A.; Wang Y.; Yu J.; Coin L.J.M.; Fang L.; Li Q.; Li, Z.; Lin H.; Liu, B.; Luo, R.; Qin, N.; Shao H.; Wang, B.; Xie, Y.; Ye, C.; Yu, C.; Zhang F.; Zheng H.; Zhu H.; Garrison, E.P.; Kural, D.; Lee W.-P.; Fung Leong W.; Ward, A.N.; Wu J.; Zhang, M.; Griffin L.; Hsieh, C.-H.; Mills, R.E.; Shi X.; Von Grotthuss, M.; Zhang, C.; Daly, M.J.; Depristo, M.A.; Banks, E.; Bhatia G.; Carneiro, M.O.; Del Angel G.; Genovese G.; Handsaker, R.E.; Hartl, C.; McCarroll, S.A.; Nemesh J.C.; Poplin, R.E.; Schaffner, S.F.; Shakir, K.; Yoon, S.C.; Lihm J.; Makarov V.; Jin H.; Kim W.; Cheol Kim, K.; Rausch, T.; Beal, K.; Cunningham F.; Herrero J.; McLaren W.M.; Ritchie G.R.S.; Gottipati, S.; Keinan, A.; Rodriguez-Flores J.L.; Sabeti P.C.; Grossman, S.R.; Tabrizi, S.; Tariyal, R.; Cooper, D.N.; Ball, E.V.; Stenson P.D.; Barnes, B.; Bauer, M.; Keira Cheetham, R.; Cox, T.; Eberle, M.; Kahn, S.; Murray L.; Peden J.; Shaw, R.; Ye, K.; Batzer, M.A.; Konkel, M.K.; Walker J.A.; MacArthur, D.G.; Lek, M.; Herwig, R.; Shriver, M.D.; Bustamante, C.D.; Byrnes J.K.; De La Vega F.M.; Gravel, S.; Kenny, E.E.; Kidd J.M.; Maples, B.K.; Moreno-Estrada, A.; Zakharia F.; Halperin, E.; Baran, Y.; Craig, D.W.; Christoforides, A.; Homer, N.; Izatt, T.; Kurdoglu, A.A.; Sinari, S.A.; Squire, K.; Xiao, C.; Sebat J.; Bafna V.; Ye, K.; Burchard, E.G.; Hernandez, R.D.; Gignoux, C.R.; Haussler, D.; Katzman, S.J.; James Kent W.; Howie, B.; Ruiz-Linares, A.; Dermitzakis, E.T.; Lappalainen, T.; Devine, S.E.; Liu X.; Maroo, A.; Tallon L.J.; Rosenfeld J.A.; Michelson L.P.; Min Kang H.; Anderson P.; Angius, A.; Bigham, A.; Blackwell, T.; Busonero F.; Cucca F.; Fuchsberger, C.; Jones, C.; Jun G.; Li Y.; Lyons, R.; Maschio, A.; Porcu, E.; Reinier F.; Sanna, S.; Schlessinger, D.; Sidore, C.; Tan, A.; Kate Trost, M.; Awadalla P.; Hodgkinson, A.; Lunter G.; Marchini J.L.; Myers, S.; Churchhouse, C.; Delaneau O.; Gupta-Hinch, A.; Iqbal, Z.; Mathieson I.; Rimmer, A.; Xifara, D.K.; Oleksyk, T.K.; Fu, Y.; Liu X.; Xiong, M.; Jorde L.; Witherspoon, D.; Xing J.; Browning, B.L.; Alkan C.; Hajirasouliha I.; Hormozdiari F.; Ko, A.; Sudmant P.H.; Chen, K.; Chinwalla, A.; Ding L.; Dooling, D.; Koboldt, D.C.; McLellan, M.D.; Wallis J.W.; Wendl, M.C.; Zhang Q.; Tyler-Smith, C.; Albers, C.A.; Ayub Q.; Chen, Y.; Coffey, A.J.; Colonna V.; Huang, N.; Jostins L.; Li H.; Scally, A.; Walter, K.; Xue, Y.; Zhang, Y.; Gerstein, M.B.; Abyzov, A.; Balasubramanian, S.; Chen J.; Clarke, D.; Fu, Y.; Habegger L.; Harmanci, A.O.; Jin, M.; Khurana, E.; Jasmine Mu X.; Sisu, C.; Degenhardt J.; Stütz, A.M.; Keira Cheetham, R.; Church, D.; Michaelson J.J.; Blackburne, B.; Lindsay, S.J.; Ning, Z.; Frankish, A.; Harrow J.; Mu X.J.; Fowler G.; Hale W.; Kalra, D.; Barker J.; Kelman G.; Kulesha, E.; Radhakrishnan, R.; Roa, A.; Smirnov, D.; Streeter I.; Toneva I.; Vaughan, B.; Ananiev V.; Belaia, Z.; Beloslyudtsev, D.; Bouk, N.; Chen, C.; 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.; Zhang H.; Barnes, K.C.; Beiswanger, C.; Cai H.; Cao H.; Gharani, N.; Henn, B.; Jones, D.; Kaye J.S.; Kent, A.; Kerasidou, A.; Mathias, R.; Ossorio P.N.; Parker, M.; Reich, D.; Rotimi, C.N.; Royal, C.D.; Sandoval, K.; Su, Y.; Tian, Z.; Tishkoff, S.; Toji L.H.; Via, M.; Wang Y.; Yang H.; Yang L.; Zhu J.; Bodmer W.; Bedoya G.; Ming, C.Z.; Yang G.; Jia You, C.; Peltonen L.; Garcia-Montero, A.; Orfao, A.; Dutil J.; Martinez-Cruzado J.C.; Brooks L.D.; Felsenfeld, A.L.; McEwen J.E.; Clemm, N.C.; Duncanson, A.; Dunn, M.; Guyer, M.S.; Peterson J.L.; Lacroute P.
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. © 2012 Macmillan Publishers Limited. All rights reserved.