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      Genome-wide patterns of selection in 230 ancient Eurasians

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      1 , 1 , 2 , 1 , 2 , 1 , 2 , 3 , 2 , 4 , 1 , 3 , 1 , 3 , 5 , 5 , 6 , 5 , 7 , 5 , 9 , 9 , 10 , 11 , 12 , 11 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 20 , 17 , 18 , 21 , 20 , 22 , 23 , 24 , 17 , 18 , 25 , 26 , 10 , 21 , 27 , 28 , 29 , 30 , 30 , 31 , 10 , 25 , 5 , 1 , 2 , 3
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          Abstract

          Ancient DNA makes it possible to directly witness natural selection by analyzing samples from populations before, during and after adaptation events. Here we report the first scan for selection using ancient DNA, capitalizing on the largest genome-wide dataset yet assembled: 230 West Eurasians dating to between 6500 and 1000 BCE, including 163 with newly reported data. The new samples include the first genome-wide data from the Anatolian Neolithic culture whose genetic material we extracted from the DNA-rich petrous bone and who we show were members of the population that was the source of Europe’s first farmers. We also report a complete transect of the steppe region in Samara between 5500 and 1200 BCE that allows us to recognize admixture from at least two external sources into steppe populations during this period. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.

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          Is Open Access

          The Sequence Alignment/Map format and SAMtools

          Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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            Is Open Access

            A global reference for human genetic variation

            The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
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              Is Open Access

              Second-generation PLINK: rising to the challenge of larger and richer datasets

              PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                7 June 2016
                23 November 2015
                24 December 2015
                24 June 2016
                : 528
                : 7583
                : 499-503
                Affiliations
                [1 ]Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
                [2 ]Broad Institute of MIT and Harvard, Cambridge Massachusetts 02142, USA
                [3 ]Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
                [4 ]Independent researcher, Santpoort-Noord, The Netherlands
                [5 ]School of Archaeology and Earth Institute, Belfield, University College Dublin, Dublin 4, Ireland
                [6 ]Institute for Anthropological Research, Zagreb 10000, Croatia
                [7 ]Department of Anthropology, Emory University, Atlanta, Georgia, USA
                [9 ]Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland
                [10 ]Australian Centre for Ancient DNA, School of Earth and Environmental Sciences & Environment Institute, University of Adelaide, Adelaide, South Australia 5005, Australia
                [11 ]Laboratory of Human Molecular Genetics, Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia
                [12 ]Department of Paleolithic Archaeology, Institute of Archaeology and Ethnography, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia
                [14 ]Centro Mixto UCM-ISCIII de Evolución y Comportamiento Humanos, Madrid, Spain
                [15 ]Departamento de Paleontología, Facultad Ciencias Geológicas, Universidad Complutense de Madrid, Spain
                [16 ]Centro Nacional de Investigacíon sobre Evolución Humana (CENIEH), 09002 Burgos, Spain
                [17 ]IPHES. Institut Català de Paleoecologia Humana i Evolució Social, Campus Sescelades-URV, 43007. Tarragona, Spain
                [18 ]Area de Prehistoria, Universitat Rovira i Virgili (URV), 43002 Tarragona, Spain
                [19 ]Netherlands Institute in Turkey, Istiklal Caddesi, Nur-i Ziya Sokak 5, Beyoğlu, Istanbul, Turkey
                [20 ]Volga State Academy of Social Sciences and Humanities, Samara 443099, Russia
                [21 ]State Office for Heritage Management and Archaeology Saxony-Anhalt and State Museum of Prehistory, D-06114 Halle, Germany
                [22 ]Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) RAS, St Petersburg, 199034, Russia
                [23 ]Department of Prehistory and Archaeology, University of Valladolid, Spain
                [24 ]The Netherlands Institute for the Near East, Leiden, RA-2300, The Netherlands
                [25 ]Max Planck Institute for the Science of Human History, D-07745 Jena, Germany
                [26 ]Institute for Archaeological Sciences, University of Tübingen, D-72070 Tübingen, Germany
                [27 ]Danube Private University, A-3500 Krems, Austria
                [28 ]Institute for Prehistory and Archaeological Science, University of Basel, CH-4003 Basel, Switzerland
                [29 ]Institute of Anthropology, Johannes Gutenberg University of Mainz, D-55128 Mainz, Germany
                [30 ]Anthropology Department, Hartwick College, Oneonta, New York 13820, USA
                [31 ]Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Barcelona, Spain
                Author notes
                Correspondence and requests for materials should be addressed to I.M. ( iain_mathieson@ 123456hms.harvard.edu ), W.H. ( haak@ 123456shh.mpg.de ), R.P. ( ron.pinhasi@ 123456ucd.ie ) or D.R. ( reich@ 123456genetics.med.harvard.edu )
                [+]

                These authors contributed equally to this work

                [8]

                Current address: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5–7, 1350 Copenhagen, Denmark

                [13]

                Current Address: New York Genome Center, New York NY, USA

                Article
                NIHMS734926
                10.1038/nature16152
                4918750
                26595274
                669dd175-fb35-4015-81be-0f6ef66649b9

                Reprints and permissions information are available at www.nature.com/reprints.

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