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      Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility

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          Abstract

          The rhesus macaque ( Macaca mulatta) is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization. With the improved assembly of segmental duplications, we discovered new lineage-specific genes and expanded gene families that are potentially informative in studies of evolution and disease susceptibility. Whole-genome sequencing (WGS) data from 853 rhesus macaques identified 85.7 million single-nucleotide variants (SNVs) and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay, providing a framework for developing noninvasive NHP models of human disease.

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          Journal
          Science
          Science
          American Association for the Advancement of Science (AAAS)
          0036-8075
          1095-9203
          December 17 2020
          December 18 2020
          December 18 2020
          December 17 2020
          : 370
          : 6523
          : eabc6617
          Affiliations
          [1 ]Department of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
          [2 ]Department of Surgery, School of Medicine, University of Missouri, Columbia, MO 65211, USA.
          [3 ]Institute of Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA.
          [4 ]Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
          [5 ]Computational Genomics Laboratory, University of California–Santa Cruz, Santa Cruz, CA 95064, USA.
          [6 ]Inscripta Inc., Boulder, CO 80301, USA.
          [7 ]Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
          [8 ]Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
          [9 ]Department of Biomolecular Engineering, University of California–Santa Cruz, Santa Cruz, CA 95064, USA.
          [10 ]Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
          [11 ]Institue for Systems Biology, Seattle, WA 98109, USA.
          [12 ]McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
          [13 ]Department of Biology, University of Bari 'Aldo Moro', 70125 Bari, Italy.
          [14 ]Pacific Biosciences of California, Seattle, WA 94025, USA.
          [15 ]Department of Pathology and Laboratory Medicine, Wisconsin National Primate Research Center, University of Wisconsin–Madison, Madison, WI 53711, USA.
          [16 ]European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
          [17 ]Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
          [18 ]Tulane National Primate Research Center, Covington, LA 70433, USA.
          [19 ]Oregon National Primate Research Center and Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Beaverton, OR 97006, USA.
          [20 ]Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53719, USA.
          [21 ]Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA.
          [22 ]Department of Neuroscience, University of Wisconsin, Madison, WI 53175, USA.
          [23 ]Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53171, USA.
          [24 ]Department of Obstetrics and Gynecology, Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
          [25 ]The University of Texas MD Anderson Cancer Center, Michale E. Keeling Center for Comparative Medicine and Research, Bastrop, TX 78602, USA.
          [26 ]Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
          [27 ]Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA.
          [28 ]Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53706, USA.
          [29 ]Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California–Davis, Davis, CA 95616, USA.
          [30 ]Department of Ophthalmology and Vision Science, School of Medicine, University of California–Davis, Davis, CA 95817, USA.
          [31 ]California National Primate Research Center, Davis, CA 95616, USA.
          [32 ]Department of Psychology, University of California, Davis, CA 95616, USA.
          [33 ]Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.
          [34 ]Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
          [35 ]Population Health Program, Texas Biomedical Research Institute and Southwest National Primate Research Center, San Antonio, TX 78227, USA.
          Article
          10.1126/science.abc6617
          7818670
          33335035
          165be39e-b503-491b-bc48-23e6d42dbc8d
          © 2020

          https://www.sciencemag.org/about/science-licenses-journal-article-reuse


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