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

Autor: Ebert P; Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany., Audano PA; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Zhu Q; The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA., Rodriguez-Martin B; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany., Porubsky D; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Bonder MJ; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.; Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Sulovari A; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Ebler J; Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany., Zhou W; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA., Serra Mari R; Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany., Yilmaz F; The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA., Zhao X; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Hsieh P; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Lee J; Bionano Genomics, San Diego, CA 92121, USA., Kumar S; Program in Computational Biology and Bioinformatics, Yale University, BASS 432 and 437, 266 Whitney Avenue, New Haven, CT 06520, USA., Lin J; School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China., Rausch T; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany., Chen Y; Department of Genetics and Informatics Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Ren J; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA., Santamarina M; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Department of Zoology, Genetics, and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Höps W; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany., Ashraf H; Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany., Chuang NT; Institute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA., Yang X; School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China., Munson KM; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Lewis AP; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Fairley S; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK., Tallon LJ; Institute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA., Clarke WE; New York Genome Center, New York, NY 10013, USA., Basile AO; New York Genome Center, New York, NY 10013, USA., Byrska-Bishop M; New York Genome Center, New York, NY 10013, USA., Corvelo A; New York Genome Center, New York, NY 10013, USA., Evani US; New York Genome Center, New York, NY 10013, USA., Lu TY; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA., Chaisson MJP; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA., Chen J; Department of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA., Li C; Department of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA., Brand H; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Wenger AM; Pacific Biosciences of California, Menlo Park, CA 94025, USA., Ghareghani M; Max Planck Institute for Informatics, Saarland Informatics Campus E1.4, 66123 Saarbrücken, Germany.; Saarbrücken Graduate School of Computer Science, Saarland University, Saarland Informatics Campus E1.3, 66123 Saarbrücken, Germany.; Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany., Harvey WT; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA., Raeder B; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany., Hasenfeld P; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany., Regier AA; Department of Medicine, Washington University, St. Louis, MO 63108, USA., Abel HJ; Department of Medicine, Washington University, St. Louis, MO 63108, USA., Hall IM; Department of Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA., Flicek P; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK., Stegle O; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany.; Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Gerstein MB; Program in Computational Biology and Bioinformatics, Yale University, BASS 432 and 437, 266 Whitney Avenue, New Haven, CT 06520, USA., Tubio JMC; Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Department of Zoology, Genetics, and Physical Anthropology, Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Mu Z; Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL 60637, USA., Li YI; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA., Shi X; Department of Computer and Information Sciences, Temple University, Philadelphia, PA 19122, USA., Hastie AR; Bionano Genomics, San Diego, CA 92121, USA., Ye K; School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.; Department of Human Genetics, University of Michigan, 1241 E. Catherine Street, Ann Arbor, MI 48109, USA., Chong Z; Department of Genetics and Informatics Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Sanders AD; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany., Zody MC; New York Genome Center, New York, NY 10013, USA., Talkowski ME; Center for Genomic Medicine, Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Mills RE; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.; Department of Human Genetics, University of Michigan, 1241 E. Catherine Street, Ann Arbor, MI 48109, USA., Devine SE; Institute for Genome Sciences, University of Maryland School of Medicine, 670 W Baltimore Street, Baltimore, MD 21201, USA., Lee C; The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.; Precision Medicine Center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.; Department of Graduate Studies-Life Sciences, Ewha Womans University, Ewhayeodae-gil, Seodaemun-gu, Seoul 120-750, South Korea., Korbel JO; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK., Marschall T; Heinrich Heine University, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Moorenstraße 20, 40225 Düsseldorf, Germany. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org., Eichler EE; Department of Genome Sciences, University of Washington School of Medicine, 3720 15th Avenue NE, Seattle, WA 98195-5065, USA. eee@gs.washington.edu tobias.marschall@hhu.de jan.korbel@embl.org charles.lee@jax.org.; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Apr 02; Vol. 372 (6537). Date of Electronic Publication: 2021 Feb 25.
DOI: 10.1126/science.abf7117
Abstrakt: 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 minimum contig length needed to cover 50% of the genome: 26 million base pairs) integrate all forms of genetic variation, even across complex loci. We identified 107,590 structural variants (SVs), of which 68% were not discovered with short-read sequencing, and 278 SV hotspots (spanning megabases of gene-rich sequence). We characterized 130 of the most active mobile element source elements and found that 63% of all SVs arise through homology-mediated mechanisms. This resource enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1526 expression quantitative trait loci as well as SV candidates for adaptive selection within the human population.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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