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

Wesley C Warren; R Alan Harris; Marina Haukness; Ian T Fiddes; Shwetha C Murali; Jason Fernandes; Philip C Dishuck; Jessica M Storer; Muthuswamy Raveendran; LaDeana W Hillier; David Porubsky; Yafei Mao; David Gordon; Mitchell R Vollger; Alexandra P Lewis; Katherine M Munson; Elizabeth DeVogelaere; Joel Armstrong; Mark Diekhans; Jerilyn A Walker; Chad Tomlinson; Tina A Graves-Lindsay; Milinn Kremitzki; Sofie R Salama; Peter A Audano; Merly Escalona; Nicholas W Maurer; Francesca Antonacci; Ludovica Mercuri; Flavia A M Maggiolini; Claudia Rita Catacchio; Jason G Underwood; David H O'Connor; Ashley D Sanders; Jan O Korbel; Betsy Ferguson; H Michael Kubisch; Louis Picker; Ned H Kalin; Douglas Rosene; Jon Levine; David H Abbott; Stanton B Gray; Mar M Sanchez; Zsofia A Kovacs-Balint; Joseph W Kemnitz; Sara M Thomasy; Jeffrey A Roberts; Erin L Kinnally; John P Capitanio; J H Pate Skene; Michael Platt; Shelley A Cole; Richard E Green; Mario Ventura; Roger W Wiseman; Benedict Paten; Mark A Batzer; Jeffrey Rogers; Evan E Eichler

doi:10.1126/science.abc6617

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

Science. 2020 Dec 18;370(6523):eabc6617. doi: 10.1126/science.abc6617.

Authors

Wesley C Warren^{1

2

3}, R Alan Harris⁴, Marina Haukness⁵, Ian T Fiddes⁶, Shwetha C Murali^{7

8}, Jason Fernandes⁹, Philip C Dishuck⁷, Jessica M Storer^{10

11}, Muthuswamy Raveendran⁴, LaDeana W Hillier⁷, David Porubsky⁷, Yafei Mao⁷, David Gordon^{7

8}, Mitchell R Vollger⁷, Alexandra P Lewis⁷, Katherine M Munson⁷, Elizabeth DeVogelaere⁵, Joel Armstrong⁵, Mark Diekhans⁵, Jerilyn A Walker¹⁰, Chad Tomlinson¹², Tina A Graves-Lindsay¹², Milinn Kremitzki¹², Sofie R Salama⁹, Peter A Audano⁷, Merly Escalona⁹, Nicholas W Maurer⁹, Francesca Antonacci¹³, Ludovica Mercuri¹³, Flavia A M Maggiolini¹³, Claudia Rita Catacchio¹³, Jason G Underwood¹⁴, David H O'Connor¹⁵, Ashley D Sanders¹⁶, Jan O Korbel¹⁶, Betsy Ferguson¹⁷, H Michael Kubisch¹⁸, Louis Picker¹⁹, Ned H Kalin²⁰, Douglas Rosene²¹, Jon Levine^{22

23}, David H Abbott^{23

24}, Stanton B Gray²⁵, Mar M Sanchez^{26

27}, Zsofia A Kovacs-Balint²⁶, Joseph W Kemnitz^{23

28}, Sara M Thomasy^{29

30}, Jeffrey A Roberts³¹, Erin L Kinnally^{31

32}, John P Capitanio^{31

32}, J H Pate Skene³³, Michael Platt³⁴, Shelley A Cole³⁵, Richard E Green⁹, Mario Ventura¹³, Roger W Wiseman¹⁵, Benedict Paten⁵, Mark A Batzer¹⁰, Jeffrey Rogers³⁶, Evan E Eichler^{37

8}

Affiliations

¹ Department of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. warrenwc@missouri.edu jr13@bcm.edu eee@gs.washington.edu.
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.
³⁶ Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. warrenwc@missouri.edu jr13@bcm.edu eee@gs.washington.edu.
³⁷ Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. warrenwc@missouri.edu jr13@bcm.edu eee@gs.washington.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Genetic Predisposition to Disease*
Genetic Variation
Genome*
Humans
Macaca mulatta / genetics*
Molecular Sequence Annotation
Polymorphism, Single Nucleotide*
Whole Genome Sequencing

Abstract

Publication types

MeSH terms

Grants and funding