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      Haplotype-resolved diverse human genomes and integrated analysis of structural variation

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          Abstract

          Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent–child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average contig N50: 26 Mbp) integrate all forms of genetic variation even across complex loci. We identify 107,590 structural variants (SVs), of which 68% are not discovered by short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterize 130 of the most active mobile element source elements and find that 63% of all SVs arise by homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1,526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.

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          Fast and cheap genome wide haplotype construction via optical mapping

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            Journal
            Science
            Science
            American Association for the Advancement of Science (AAAS)
            0036-8075
            1095-9203
            February 25 2021
            : eabf7117
            Affiliations
            [1 ]Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstr. 20, 40225 Düsseldorf, Germany
            [2 ]Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Ave NE, Seattle, WA 98195-5065, USA
            [3 ]The Jackson Laboratory for Genomic Medicine, 10 Discovery Dr, Farmington, CT 06032, USA
            [4 ]European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany
            [5 ]Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
            [6 ]Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA
            [7 ]Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA
            [8 ]Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
            [9 ]Bionano Genomics, San Diego, CA 92121, USA
            [10 ]Program in Computational Biology and Bioinformatics, Yale University, BASS 432&437, 266 Whitney Avenue, New Haven, CT 06520, USA
            [11 ]School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, China
            [12 ]Department of Genetics and Informatics Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
            [13 ]Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA
            [14 ]Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
            [15 ]Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
            [16 ]Institute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA
            [17 ]School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, China
            [18 ]European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom
            [19 ]New York Genome Center, New York, NY 10013, USA
            [20 ]Department of Computer & Information Sciences, Temple University, Philadelphia, PA 19122, USA
            [21 ]Pacific Biosciences of California, Inc., Menlo Park, CA 94025, USA
            [22 ]Max Planck Institute for Informatics, Saarland Informatics Campus E1.4, 66123 Saarbrücken, Germany
            [23 ]Saarbrücken Graduate School of Computer Science, Saarland University, Saarland Informatics Campus E1.3, 66123 Saarbrücken, Germany
            [24 ]Washington University, St. Louis, MO 63108, USA
            [25 ]Department of Genetics, Yale School of Medicine, 333 Cedar St., New Haven, CT 06510 USA
            [26 ]Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL 60637 USA
            [27 ]Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637 USA
            [28 ]Department of Human Genetics, University of Michigan, 1241 E. Catherine St., Ann Arbor, MI 48109, USA
            [29 ]Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Rd., Xi'an, 710061, Shaanxi, China
            [30 ]Department of Graduate Studies – Life Sciences, Ewha Womans University, Ewhayeodae-gil, Seodaemun-gu, Seoul, South Korea 120-750
            [31 ]Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
            Article
            10.1126/science.abf7117
            33632895
            bd65ac4b-b573-4d30-afbc-08e07a053abc
            © 2021
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