Global diversity, population stratification, and selection of human copy-number variation

doi:10.1126/science.aab3761

Comparative Study

. 2015 Sep 11;349(6253):aab3761.

doi: 10.1126/science.aab3761. Epub 2015 Aug 6.

Global diversity, population stratification, and selection of human copy-number variation

Peter H Sudmant¹, Swapan Mallick², Bradley J Nelson¹, Fereydoun Hormozdiari¹, Niklas Krumm¹, John Huddleston³, Bradley P Coe¹, Carl Baker¹, Susanne Nordenfelt², Michael Bamshad⁴, Lynn B Jorde⁵, Olga L Posukh⁶, Hovhannes Sahakyan⁷, W Scott Watkins⁸, Levon Yepiskoposyan⁹, M Syafiq Abdullah¹⁰, Claudio M Bravi¹¹, Cristian Capelli¹², Tor Hervig¹³, Joseph T S Wee¹⁴, Chris Tyler-Smith¹⁵, George van Driem¹⁶, Irene Gallego Romero¹⁷, Aashish R Jha¹⁷, Sena Karachanak-Yankova¹⁸, Draga Toncheva¹⁸, David Comas¹⁹, Brenna Henn²⁰, Toomas Kivisild²¹, Andres Ruiz-Linares²², Antti Sajantila²³, Ene Metspalu²⁴, Jüri Parik²⁵, Richard Villems²⁵, Elena B Starikovskaya²⁶, George Ayodo²⁷, Cynthia M Beall²⁸, Anna Di Rienzo¹⁷, Michael F Hammer²⁹, Rita Khusainova³⁰, Elza Khusnutdinova³⁰, William Klitz³¹, Cheryl Winkler³², Damian Labuda³³, Mait Metspalu²⁵, Sarah A Tishkoff³⁴, Stanislav Dryomov³⁵, Rem Sukernik³⁶, Nick Patterson², David Reich³⁷, Evan E Eichler³⁸

Affiliations

¹ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
² Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
³ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
⁴ Department of Pediatrics, University of Washington, Seattle, WA 98119, USA.
⁵ Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
⁶ Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Novosibirsk State University, Novosibirsk 630090, Russia.
⁷ Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.
⁸ Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
⁹ Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.
¹⁰ Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan, Brunei Darussalam.
¹¹ Laboratorio de Genética Molecular Poblacional, Instituto Multidisciplinario de Biología Celular (IMBICE), Centro Científico y Tecnológico-Consejo Nacional de Investigaciones Científicas y Técnicas (CCT-CONICET) and Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CICPBA), La Plata B1906APO, Argentina.
¹² Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
¹³ Department of Clinical Science, University of Bergen, Bergen 5021, Norway.
¹⁴ National Cancer Centre Singapore, Singapore.
¹⁵ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
¹⁶ Institute of Linguistics, University of Bern, Bern CH-3012, Switzerland.
¹⁷ Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
¹⁸ Department of Medical Genetics, National Human Genome Center, Medical University Sofia, Sofia 1431, Bulgaria.
¹⁹ Institut de Biologia Evolutiva [Consejo Superior de Investigaciones Científicas-Universitat Pompeu Fabra (CSIC-UPF)], Departament de Ciències Experimentals i de la Salut, UPF, Barcelona 08003, Spain.
²⁰ Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794, USA.
²¹ Division of Biological Anthropology, University of Cambridge, Fitzwilliam Street, Cambridge CB2 1QH, UK.
²² Department of Genetics, Evolution and Environment, University College London, WC1E 6BT, UK.
²³ University of Helsinki, Department of Forensic Medicine, Helsinki 00014, Finland.
²⁴ Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. University of Tartu, Department of Evolutionary Biology, Tartu 5101, Estonia.
²⁵ Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia.
²⁶ Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
²⁷ Center for Global Health and Child Development, Kisumu 40100, Kenya.
²⁸ Department of Anthropology, Case Western Reserve University, Cleveland, OH 44106-7125, USA.
²⁹ Arizona Research Laboratories Division of Biotechnology, University of Arizona, Tucson, AZ 85721, USA.
³⁰ Institute of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Sciences, Ufa 450054, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa 450074, Russia.
³¹ Integrative Biology, University of California, Berkeley, CA 94720-3140, USA.
³² Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Incorporated, Frederick National Laboratory, Frederick, MD 21702, USA.
³³ Centre Hospitalier Universitaire (CHU) Sainte-Justine, Département de Pédiatrie, Université de Montréal, QC H3T 1C5, Canada.
³⁴ Departments of Biology and Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
³⁵ Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Department of Paleolithic Archaeology, Institute of Archaeology and Ethnography, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
³⁶ Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Altai State University, Barnaul 656000, Russia.
³⁷ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
³⁸ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. eee@gs.washington.edu.

PMID: 26249230
PMCID: PMC4568308
DOI: 10.1126/science.aab3761

Comparative Study

Global diversity, population stratification, and selection of human copy-number variation

Peter H Sudmant et al. Science. 2015.

. 2015 Sep 11;349(6253):aab3761.

doi: 10.1126/science.aab3761. Epub 2015 Aug 6.

Authors

Affiliations

¹ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
² Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
³ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
⁴ Department of Pediatrics, University of Washington, Seattle, WA 98119, USA.
⁵ Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
⁶ Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Novosibirsk State University, Novosibirsk 630090, Russia.
⁷ Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.
⁸ Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
⁹ Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences of Armenia, Yerevan 0014, Armenia.
¹⁰ Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital, Bandar Seri Begawan, Brunei Darussalam.
¹¹ Laboratorio de Genética Molecular Poblacional, Instituto Multidisciplinario de Biología Celular (IMBICE), Centro Científico y Tecnológico-Consejo Nacional de Investigaciones Científicas y Técnicas (CCT-CONICET) and Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CICPBA), La Plata B1906APO, Argentina.
¹² Department of Zoology, University of Oxford, Oxford OX1 3PS, UK.
¹³ Department of Clinical Science, University of Bergen, Bergen 5021, Norway.
¹⁴ National Cancer Centre Singapore, Singapore.
¹⁵ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
¹⁶ Institute of Linguistics, University of Bern, Bern CH-3012, Switzerland.
¹⁷ Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
¹⁸ Department of Medical Genetics, National Human Genome Center, Medical University Sofia, Sofia 1431, Bulgaria.
¹⁹ Institut de Biologia Evolutiva [Consejo Superior de Investigaciones Científicas-Universitat Pompeu Fabra (CSIC-UPF)], Departament de Ciències Experimentals i de la Salut, UPF, Barcelona 08003, Spain.
²⁰ Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY 11794, USA.
²¹ Division of Biological Anthropology, University of Cambridge, Fitzwilliam Street, Cambridge CB2 1QH, UK.
²² Department of Genetics, Evolution and Environment, University College London, WC1E 6BT, UK.
²³ University of Helsinki, Department of Forensic Medicine, Helsinki 00014, Finland.
²⁴ Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia. University of Tartu, Department of Evolutionary Biology, Tartu 5101, Estonia.
²⁵ Estonian Biocentre, Evolutionary Biology Group, Tartu 51010, Estonia.
²⁶ Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
²⁷ Center for Global Health and Child Development, Kisumu 40100, Kenya.
²⁸ Department of Anthropology, Case Western Reserve University, Cleveland, OH 44106-7125, USA.
²⁹ Arizona Research Laboratories Division of Biotechnology, University of Arizona, Tucson, AZ 85721, USA.
³⁰ Institute of Biochemistry and Genetics, Ufa Research Centre, Russian Academy of Sciences, Ufa 450054, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa 450074, Russia.
³¹ Integrative Biology, University of California, Berkeley, CA 94720-3140, USA.
³² Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical Research, Incorporated, Frederick National Laboratory, Frederick, MD 21702, USA.
³³ Centre Hospitalier Universitaire (CHU) Sainte-Justine, Département de Pédiatrie, Université de Montréal, QC H3T 1C5, Canada.
³⁴ Departments of Biology and Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
³⁵ Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Department of Paleolithic Archaeology, Institute of Archaeology and Ethnography, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
³⁶ Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia. Altai State University, Barnaul 656000, Russia.
³⁷ Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
³⁸ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. eee@gs.washington.edu.

PMID: 26249230
PMCID: PMC4568308
DOI: 10.1126/science.aab3761

Abstract

In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load.

PubMed Disclaimer

Figures

**Fig. 1. Analysis of CNVs in several world populations**
The geographical locations of the 125 human populations, including two archaic genomes, assessed in this study. Populations are colored by their continental population groups, and archaic individuals are indicated in black.

**Fig. 2. Population structure and CNV diversity**
Principal component analysis (PCA) of individuals assessed in this study plotted for bi-allelic deletions (A) and duplications (B) with colors and shapes representing continental and specific populations, respectively. Individuals are projected along the PC1 and PC2 axes. The deletion (C) and duplication (D) heterozygosity plotted and grouped by continental population. The relationship between SNV heterozygosity and deletion (E) or duplication (F) heterozygosity is compared.

**Fig. 3. Selection on CNVs**
Folded allele frequency spectra of exon-intersecting deletions (A) and duplications (B). While deletions intersecting exons are significantly rarer than intergenic deletions, exon-intersecting duplications show no difference compared to intergenic duplications. The mean frequency of CNVs beyond a minimum size threshold is plotted for deletions (C) and duplications (D). A strong negative correlation between size and allele frequency is observed for deletions but less so for duplications.

**Fig. 4. Population-stratified CNVs and archaic introgression**
(A) Four specific examples of population-stratified CNVs intersecting genes are shown, including *LRRIQ3*, the pancreatic collipase *CLPS*, the sperm head an acrosome formation gene *DPY19L2*, and the haptoglobin and haptoglobin-related genes HP and *HPR*. Dot-plots indicating the copy of the locus in each individual and pie charts with colors depicting the continental population distribution per copy number (see text for details and Figs. 1 and 2 and dot plots for color scheme). (B) Predicted copy number on the basis of read-depth for a 73.5 kbp duplication on chromosome 16. It is observed in the archaic Denisovan genome and at 0.84 allele frequency in Papuan and Bougainville populations, yet absent from all other assessed populations. The duplication intersects two microRNAs. The orange arrow corresponds to the position and orientation of this duplication as further highlighted in (C) and (D). (C) A heatmap representation of a ~1 Mbp region of chromosome 16p12 (chr16:21518638-22805719). Each row of the heatmap represents the estimated copy number in 1 kbp windows of a single individual across this locus. Genes, annotated segmental duplications, and arrows highlighting the size and orientation in the reference of the Denisova/Papuan-specific duplication locus (locus D) and three other duplicated loci (A, B, and C) of interest are shown below. (D) The structure of duplications A, B, C and D (as shown in 4C over the same locus) in the reference genome and the discordant paired-end read placements used to characterize two duplication structures. Structure A/C is found in all individuals, though not present in the reference genome, while structure B/D is only found in Papuan and Bougainville individuals indicating a large complex, duplication (~225 kbp) composed of different segmental duplications. Both the A/C and B/D duplication architectures exhibit inverted orientations compared to the reference. The number of reads in all Oceanic and non-Oceanic individuals supporting each structure are indicated. (E) Maximum likelihood tree of the 16p12 duplication locus (duplication D in 4B, 4C, and 4D) constructed from the locus in Orangutan, Denisova, the human reference and the inferred sequence of the Papuan duplication (24). All bootstrap values are 100%.

**Fig. 5. The ancestral human genome and CNV burden**
(A) A heatmap of the allele frequency of 571 (1.55 Mbp) nonrepetitive sequences absent from the human reference genome yet segregating in at least one human population ordered in humans by a maximum likelihood tree (49). Four groups of interest are highlighted: G1 – ancestral sequences that have almost been completely lost from the human lineage, G2 – ancestral sequences that are largely fixed but rarely deleted (also absent in human reference), G3 – ancestral sequences that have become copy number variable since the divergence of humans and Neanderthals/Denisovans ~700 kya, and G4 – sequences potentially lost in Neanderthals and Denisovans since their divergence from humans. (B) The resulting distributions of 10,000 block-bootstrapped estimates of the difference in load between African (AFR) and non-African (nAFR) populations considering only the reference genome (GRCh37) and supplemented by sequence absent from the human reference genome (GRCh37 + NHP) included (see text for details). (C) Violin plots of the distribution of the ratio of deletion base pairs to SNV base pairs differing between every pair of African individuals (AFR-AFR), all pairs of non-African individuals (nAFR-nAFR) and every non-African, African pair (nAFR-AFR). (D) Heatmap representation of the mean ratio of deletion to SNV base pairs differing between individuals from pairs of populations.

See this image and copyright information in PMC

Cited by

Copy Number Variation in TAS2R Bitter Taste Receptor Genes: Structure, Origin, and Population Genetics.
Roudnitzky N, Risso D, Drayna D, Behrens M, Meyerhof W, Wooding SP. Roudnitzky N, et al. Chem Senses. 2016 Oct;41(8):649-59. doi: 10.1093/chemse/bjw067. Epub 2016 Jun 23. Chem Senses. 2016. PMID: 27340135 Free PMC article.
The p53-inducible CLDN7 regulates colorectal tumorigenesis and has prognostic significance.
Hou Y, Hou L, Liang Y, Zhang Q, Hong X, Wang Y, Huang X, Zhong T, Pang W, Xu C, Zhu L, Li L, Fang J, Meng X. Hou Y, et al. Neoplasia. 2020 Nov;22(11):590-603. doi: 10.1016/j.neo.2020.09.001. Epub 2020 Sep 28. Neoplasia. 2020. PMID: 32992138 Free PMC article.
A high-quality human reference panel reveals the complexity and distribution of genomic structural variants.
Hehir-Kwa JY, Marschall T, Kloosterman WP, Francioli LC, Baaijens JA, Dijkstra LJ, Abdellaoui A, Koval V, Thung DT, Wardenaar R, Renkens I, Coe BP, Deelen P, de Ligt J, Lameijer EW, van Dijk F, Hormozdiari F; Genome of the Netherlands Consortium; Uitterlinden AG, van Duijn CM, Eichler EE, de Bakker PI, Swertz MA, Wijmenga C, van Ommen GB, Slagboom PE, Boomsma DI, Schönhuth A, Ye K, Guryev V. Hehir-Kwa JY, et al. Nat Commun. 2016 Oct 6;7:12989. doi: 10.1038/ncomms12989. Nat Commun. 2016. PMID: 27708267 Free PMC article.
Copy Number Variants in Two Northernmost Cattle Breeds Are Related to Their Adaptive Phenotypes.
Buggiotti L, Yudin NS, Larkin DM. Buggiotti L, et al. Genes (Basel). 2022 Sep 6;13(9):1595. doi: 10.3390/genes13091595. Genes (Basel). 2022. PMID: 36140763 Free PMC article.
Genomic structural variation: A complex but important driver of human evolution.
Soto DC, Uribe-Salazar JM, Shew CJ, Sekar A, McGinty SP, Dennis MY. Soto DC, et al. Am J Biol Anthropol. 2023 Aug;181 Suppl 76(Suppl 76):118-144. doi: 10.1002/ajpa.24713. Epub 2023 Feb 16. Am J Biol Anthropol. 2023. PMID: 36794631 Free PMC article. Review.

See all "Cited by" articles

References

1. Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM. Complete Khoisan and Bantu genomes from southern Africa. Nature. 2010;463:943–947. Medline doi:10.1038/nature08795. - PMC - PubMed
1. Steinberg KM, Antonacci F, Sudmant PH, Kidd JM, Campbell CD, Vives L, Malig M, Scheinfeldt L, Beggs W, Ibrahim M, Lema G, Nyambo TB, Omar SA, Bodo JM, Froment A, Donnelly MP, Kidd KK, Tishkoff SA, Eichler EE. Structural diversity and African origin of the 17q21.31 inversion polymorphism. Nat. Genet. 2012;44:872–880. Medline doi:10.1038/ng.2335. - PMC - PubMed
1. Gravel S, Zakharia F, Moreno-Estrada A, Byrnes JK, Muzzio M, Rodriguez-Flores JL, Kenny EE, Gignoux CR, Maples BK, Guiblet W, Dutil J, Via M, Sandoval K, Bedoya G, Oleksyk TK, Ruiz-Linares A, Burchard EG, Martinez-Cruzado JC, Bustamante CD. 1000 Genomes Project, Reconstructing Native American migrations from whole-genome and whole-exome data. PLOS Genet. 2013;9:e1004023. Medline. - PMC - PubMed
1. Raghavan M, DeGiorgio M, Albrechtsen A, Moltke I, Skoglund P, Korneliussen TS, Grønnow B, Appelt M, Gulløv HC, Friesen TM, Fitzhugh W, Malmström H, Rasmussen S, Olsen J, Melchior L, Fuller BT, Fahrni SM, Stafford T, Jr., Grimes V, Renouf MA, Cybulski J, Lynnerup N, Lahr MM, Britton K, Knecht R, Arneborg J, Metspalu M, Cornejo OE, Malaspinas AS, Wang Y, Rasmussen M, Raghavan V, Hansen TV, Khusnutdinova E, Pierre T, Dneprovsky K, Andreasen C, Lange H, Hayes MG, Coltrain J, Spitsyn VA, Götherström A, Orlando L, Kivisild T, Villems R, Crawford MH, Nielsen FC, Dissing J, Heinemeier J, Meldgaard M, Bustamante C, O’Rourke DH, Jakobsson M, Gilbert MT, Nielsen R, Willerslev E. The genetic prehistory of the New World Arctic. Science. 2014;345:1255832. Medline doi:10.1126/science.1255832. - PubMed
1. Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Z, Gusic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PL, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. A draft sequence of the Neandertal genome. Science. 2010;328:710–722. Medline doi:10.1126/science.1188021. - PMC - PubMed

Publication types

Actions
Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations

[1] Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM. Complete Khoisan and Bantu genomes from southern Africa. Nature. 2010;463:943–947. Medline doi:10.1038/nature08795. - PMC - PubMed

[2] Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM. Complete Khoisan and Bantu genomes from southern Africa. Nature. 2010;463:943–947. Medline doi:10.1038/nature08795. - PMC - PubMed

[3] Steinberg KM, Antonacci F, Sudmant PH, Kidd JM, Campbell CD, Vives L, Malig M, Scheinfeldt L, Beggs W, Ibrahim M, Lema G, Nyambo TB, Omar SA, Bodo JM, Froment A, Donnelly MP, Kidd KK, Tishkoff SA, Eichler EE. Structural diversity and African origin of the 17q21.31 inversion polymorphism. Nat. Genet. 2012;44:872–880. Medline doi:10.1038/ng.2335. - PMC - PubMed

[4] Steinberg KM, Antonacci F, Sudmant PH, Kidd JM, Campbell CD, Vives L, Malig M, Scheinfeldt L, Beggs W, Ibrahim M, Lema G, Nyambo TB, Omar SA, Bodo JM, Froment A, Donnelly MP, Kidd KK, Tishkoff SA, Eichler EE. Structural diversity and African origin of the 17q21.31 inversion polymorphism. Nat. Genet. 2012;44:872–880. Medline doi:10.1038/ng.2335. - PMC - PubMed

[5] Gravel S, Zakharia F, Moreno-Estrada A, Byrnes JK, Muzzio M, Rodriguez-Flores JL, Kenny EE, Gignoux CR, Maples BK, Guiblet W, Dutil J, Via M, Sandoval K, Bedoya G, Oleksyk TK, Ruiz-Linares A, Burchard EG, Martinez-Cruzado JC, Bustamante CD. 1000 Genomes Project, Reconstructing Native American migrations from whole-genome and whole-exome data. PLOS Genet. 2013;9:e1004023. Medline. - PMC - PubMed

[6] Gravel S, Zakharia F, Moreno-Estrada A, Byrnes JK, Muzzio M, Rodriguez-Flores JL, Kenny EE, Gignoux CR, Maples BK, Guiblet W, Dutil J, Via M, Sandoval K, Bedoya G, Oleksyk TK, Ruiz-Linares A, Burchard EG, Martinez-Cruzado JC, Bustamante CD. 1000 Genomes Project, Reconstructing Native American migrations from whole-genome and whole-exome data. PLOS Genet. 2013;9:e1004023. Medline. - PMC - PubMed

[7] Raghavan M, DeGiorgio M, Albrechtsen A, Moltke I, Skoglund P, Korneliussen TS, Grønnow B, Appelt M, Gulløv HC, Friesen TM, Fitzhugh W, Malmström H, Rasmussen S, Olsen J, Melchior L, Fuller BT, Fahrni SM, Stafford T, Jr., Grimes V, Renouf MA, Cybulski J, Lynnerup N, Lahr MM, Britton K, Knecht R, Arneborg J, Metspalu M, Cornejo OE, Malaspinas AS, Wang Y, Rasmussen M, Raghavan V, Hansen TV, Khusnutdinova E, Pierre T, Dneprovsky K, Andreasen C, Lange H, Hayes MG, Coltrain J, Spitsyn VA, Götherström A, Orlando L, Kivisild T, Villems R, Crawford MH, Nielsen FC, Dissing J, Heinemeier J, Meldgaard M, Bustamante C, O’Rourke DH, Jakobsson M, Gilbert MT, Nielsen R, Willerslev E. The genetic prehistory of the New World Arctic. Science. 2014;345:1255832. Medline doi:10.1126/science.1255832. - PubMed

[8] Raghavan M, DeGiorgio M, Albrechtsen A, Moltke I, Skoglund P, Korneliussen TS, Grønnow B, Appelt M, Gulløv HC, Friesen TM, Fitzhugh W, Malmström H, Rasmussen S, Olsen J, Melchior L, Fuller BT, Fahrni SM, Stafford T, Jr., Grimes V, Renouf MA, Cybulski J, Lynnerup N, Lahr MM, Britton K, Knecht R, Arneborg J, Metspalu M, Cornejo OE, Malaspinas AS, Wang Y, Rasmussen M, Raghavan V, Hansen TV, Khusnutdinova E, Pierre T, Dneprovsky K, Andreasen C, Lange H, Hayes MG, Coltrain J, Spitsyn VA, Götherström A, Orlando L, Kivisild T, Villems R, Crawford MH, Nielsen FC, Dissing J, Heinemeier J, Meldgaard M, Bustamante C, O’Rourke DH, Jakobsson M, Gilbert MT, Nielsen R, Willerslev E. The genetic prehistory of the New World Arctic. Science. 2014;345:1255832. Medline doi:10.1126/science.1255832. - PubMed

[9] Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Z, Gusic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PL, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. A draft sequence of the Neandertal genome. Science. 2010;328:710–722. Medline doi:10.1126/science.1188021. - PMC - PubMed

[10] Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Z, Gusic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PL, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. A draft sequence of the Neandertal genome. Science. 2010;328:710–722. Medline doi:10.1126/science.1188021. - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Global diversity, population stratification, and selection of human copy-number variation

Affiliations

Global diversity, population stratification, and selection of human copy-number variation

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Associated data

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources