The landscape of tolerated genetic variation in humans and primates-Reference-Cited by-同舟云学术

The landscape of tolerated genetic variation in humans and primates

Published:2023-06-02 Issue:6648 Volume:380 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Gao Hong¹^ORCID,Hamp Tobias¹,Ede Jeffrey¹,Schraiber Joshua G.¹,McRae Jeremy¹^ORCID,Singer-Berk Moriel²^ORCID,Yang Yanshen¹,Dietrich Anastasia S. D.¹^ORCID,Fiziev Petko P.¹^ORCID,Kuderna Lukas F. K.¹³^ORCID,Sundaram Laksshman¹^ORCID,Wu Yibing¹,Adhikari Aashish¹^ORCID,Field Yair¹^ORCID,Chen Chen¹,Batzoglou Serafim¹,Aguet Francois¹^ORCID,Lemire Gabrielle²⁴,Reimers Rebecca⁴⁵,Balick Daniel⁵⁶^ORCID,Janiak Mareike C.⁷^ORCID,Kuhlwilm Martin³⁸⁹^ORCID,Orkin Joseph D.³¹⁰^ORCID,Manu Shivakumara¹¹¹²^ORCID,Valenzuela Alejandro³^ORCID,Bergman Juraj¹³¹⁴^ORCID,Rousselle Marjolaine¹³^ORCID,Silva Felipe Ennes¹⁵¹⁶^ORCID,Agueda Lidia¹⁷^ORCID,Blanc Julie¹⁷^ORCID,Gut Marta¹⁷^ORCID,de Vries Dorien⁷^ORCID,Goodhead Ian⁷^ORCID,Harris R. Alan¹⁸^ORCID,Raveendran Muthuswamy¹⁸^ORCID,Jensen Axel¹⁹^ORCID,Chuma Idriss S.²⁰^ORCID,Horvath Julie E.²¹²²²³²⁴²⁵^ORCID,Hvilsom Christina²⁶^ORCID,Juan David³^ORCID,Frandsen Peter²⁶^ORCID,de Melo Fabiano R.²⁷^ORCID,Bertuol Fabrício²⁸^ORCID,Byrne Hazel²⁹^ORCID,Sampaio Iracilda³⁰,Farias Izeni²⁸^ORCID,do Amaral João Valsecchi³¹³²³³^ORCID,Messias Mariluce³⁴³⁵^ORCID,da Silva Maria N. F.³⁶^ORCID,Trivedi Mihir¹²,Rossi Rogerio³⁷^ORCID,Hrbek Tomas²⁸³⁸^ORCID,Andriaholinirina Nicole³⁹,Rabarivola Clément J.³⁹,Zaramody Alphonse³⁹,Jolly Clifford J.⁴⁰,Phillips-Conroy Jane⁴¹^ORCID,Wilkerson Gregory⁴²^ORCID,Abee Christian⁴²,Simmons Joe H.⁴²^ORCID,Fernandez-Duque Eduardo⁴³⁴⁴^ORCID,Kanthaswamy Sree⁴⁵,Shiferaw Fekadu⁴⁶,Wu Dongdong⁴⁷^ORCID,Zhou Long⁴⁸^ORCID,Shao Yong⁴⁷^ORCID,Zhang Guojie⁴⁸⁴⁹⁴⁷⁵⁰⁵¹^ORCID,Keyyu Julius D.⁵²^ORCID,Knauf Sascha⁵³^ORCID,Le Minh D.⁵⁴^ORCID,Lizano Esther³⁵⁵^ORCID,Merker Stefan⁵⁶^ORCID,Navarro Arcadi³⁵⁷⁵⁸⁵⁹^ORCID,Bataillon Thomas¹³^ORCID,Nadler Tilo⁶⁰,Khor Chiea Chuen⁶¹,Lee Jessica⁶²^ORCID,Tan Patrick⁶¹⁶³⁶⁴^ORCID,Lim Weng Khong⁶³⁶⁴⁶⁵^ORCID,Kitchener Andrew C.⁶⁶⁶⁷^ORCID,Zinner Dietmar⁶⁸⁶⁹⁷⁰^ORCID,Gut Ivo¹⁷⁷¹^ORCID,Melin Amanda⁷²⁷³⁷⁴^ORCID,Guschanski Katerina¹⁹⁷⁵^ORCID,Schierup Mikkel Heide¹³^ORCID,Beck Robin M. D.⁷^ORCID,Umapathy Govindhaswamy¹¹¹²^ORCID,Roos Christian⁷⁶^ORCID,Boubli Jean P.⁷^ORCID,Lek Monkol⁷⁷,Sunyaev Shamil⁵⁶^ORCID,O’Donnell-Luria Anne²⁴⁷⁸^ORCID,Rehm Heidi L.²⁷⁷⁷⁹^ORCID,Xu Jinbo¹⁸⁰^ORCID,Rogers Jeffrey¹⁸^ORCID,Marques-Bonet Tomas³¹⁷⁵⁵⁵⁷^ORCID,Farh Kyle Kai-How¹^ORCID

Affiliation:

1. Illumina Artificial Intelligence Laboratory, Illumina Inc., Foster City, CA, 94404, USA.

2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Boston, MA, 02142, USA.

3. Institute of Evolutionary Biology (UPF-CSIC), PRBB, Dr. Aiguader 88, 08003 Barcelona, Spain.

4. Division of Genetics and Genomics, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA.

5. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.

6. Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA.

7. School of Science, Engineering & Environment, University of Salford, Salford M5 4WT, UK.

8. Department of Evolutionary Anthropology, University of Vienna, Djerassiplatz 1, 1030 Vienna, Austria.

9. Human Evolution and Archaeological Sciences (HEAS), University of Vienna, 1030 Vienna, Austria.

10. Département d'anthropologie, Université de Montréal, 3150 Jean-Brillant, Montréal, QC H3T 1N8, Canada.

11. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

12. Laboratory for the Conservation of Endangered Species, CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India.

13. Bioinformatics Research Centre, Aarhus University, Aarhus 8000, Denmark.

14. Section for Ecoinformatics & Biodiversity, Department of Biology, Aarhus University, 8000 Aarhus, Denmark.

15. Research Group on Primate Biology and Conservation, Mamirauá Institute for Sustainable Development, Estrada da Bexiga 2584, Tefé, Amazonas, CEP 69553-225, Brazil.

16. Evolutionary Biology and Ecology (EBE), Département de Biologie des Organismes, Université libre de Bruxelles (ULB), Av. Franklin D. Roosevelt 50, CP 160/12, B-1050 Brussels, Belgium.

17. CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 4, 08028 Barcelona, Spain.

18. Human Genome Sequencing Center and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

19. Department of Ecology and Genetics, Animal Ecology, Uppsala University, SE-75236 Uppsala, Sweden.

20. Tanzania National Parks, Arusha, Tanzania.

21. North Carolina Museum of Natural Sciences, Raleigh, NC 27601, USA.

22. Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA.

23. Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA.

24. Department of Evolutionary Anthropology, Duke University, Durham, NC 27708, USA.

25. Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

26. Copenhagen Zoo, 2000 Frederiksberg, Denmark.

27. Universidade Federal de Viçosa, Viçosa, 36570-900, Brazil.

28. Universidade Federal do Amazonas, Departamento de Genética, Laboratório de Evolução e Genética Animal (LEGAL), Manaus, Amazonas, 69080-900, Brazil.

29. Department of Anthropology, University of Utah, Salt Lake City, UT 84102, USA.

30. Universidade Federal do Para, Guamá, Belém - PA, 66075-110, Brazil.

31. Research Group on Terrestrial Vertebrate Ecology, Mamirauá Institute for Sustainable Development, Tefé, Amazonas, 69553-225, Brazil.

32. Rede de Pesquisa para Estudos sobre Diversidade, Conservação e Uso da Fauna na Amazônia – RedeFauna, Manaus, Amazonas, 69080-900, Brazil.

33. Comunidad de Manejo de Fauna Silvestre en la Amazonía y en Latinoamérica – ComFauna, Iquitos, Loreto, 16001, Peru.

34. Universidade Federal de Rondonia, Porto Velho, Rondônia, 78900-000, Brazil.

35. PPGREN - Programa de Pós-Graduação “Conservação e Uso dos Recursos Naturais and BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Rede BIONORTE, Universidade Federal de Rondonia, Porto Velho, Rondônia, 78900-000, Brazil.

36. Instituto Nacional de Pesquisas da Amazonia, Petrópolis, Manaus - AM, 69067-375, Brazil.

37. Universidade Federal do Mato Grosso, Boa Esperança, Cuiabá - MT, 78060-900, Brazil.

38. Department of Biology, Trinity University, San Antonio, TX 78212, USA.

39. Life Sciences and Environment, Technology and Environment of Mahajanga, University of Mahajanga, Mahajanga, 401, Madagascar.

40. New York University, New York City, NY 10012, USA.

41. Washington University in St. Louis, St. Louis, MO 63130, USA.

42. Keeling Center for Comparative Medicine and Research, MD Anderson Cancer Center, Houston, TX 77030, USA.

43. Yale University, New Haven, CT 06520, USA.

44. Universidad Nacional de Formosa, Argentina Fundacion ECO, Formosa, Argentina.

45. Arizona State University, Tempe, AZ 85281, USA.

46. Guinea Worm Eradication Program, The Carter Center Ethiopia, PoB 16316, Addis Ababa 1000, Ethiopia.

47. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.

48. Center for Evolutionary & Organismal Biology, Zhejiang University School of Medicine, Hangzhou 310058, China.

49. Villum Center for Biodiversity Genomics, Section for Ecology and Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark.

50. Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China.

51. Women’s Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Shangcheng District, Hangzhou 310006, China.

52. Tanzania Wildlife Research Institute (TAWIRI), Head Office, P.O. Box 661, Arusha, Tanzania.

53. Institute of International Animal Health/One Health, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald - Insei Riems, Germany.

54. Department of Environmental Ecology, Faculty of Environmental Sciences, University of Science and Central Institute for Natural Resources and Environmental Studies, Vietnam National University, Hanoi 100000, Vietnam.

55. Catalan Institution of Research and Advanced Studies (ICREA), Passeig de Lluís Companys, 23, 08010 Barcelona, Spain.

56. Department of Zoology, State Museum of Natural History Stuttgart, 70191 Stuttgart, Germany.

57. Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Edifici ICTA-ICP, c/ Columnes s/n, 08193 Cerdanyola del Vallès, Barcelona, Spain.

58. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Av. Doctor Aiguader, N88, 08003 Barcelona, Spain.

59. BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, C. Wellington 30, 08005 Barcelona, Spain.

60. Cuc Phuong Commune, Nho Quan District, Ninh Binh Province 430000, Vietnam.

61. Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore 138672, Republic of Singapore.

62. Mandai Nature, 80 Mandai Lake Road, Singapore 729826, Republic of Singapore.

63. SingHealth Duke-NUS Institute of Precision Medicine (PRISM), Singapore 168582, Republic of Singapore.

64. Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 168582, Republic of Singapore.

65. SingHealth Duke-NUS Genomic Medicine Centre, Singapore 168582, Republic of Singapore.

66. Department of Natural Sciences, National Museums Scotland, Chambers Street, Edinburgh EH1 1JF, UK.

67. School of Geosciences, University of Edinburgh, Drummond Street, Edinburgh EH8 9XP, UK.

68. Cognitive Ethology Laboratory, Germany Primate Center, Leibniz Institute for Primate Research, 37077 Göttingen, Germany.

69. Department of Primate Cognition, Georg-August-Universität Göttingen, 37077 Göttingen, Germany.

70. Leibniz Science Campus Primate Cognition, 37077 Göttingen, Germany.

71. Universitat Pompeu Fabra, Pg. Luís Companys 23, 08010 Barcelona, Spain.

72. Department of Anthropology & Archaeology, University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.

73. Department of Medical Genetics, 3330 Hospital Drive NW, HMRB 202, Calgary, AB T2N 4N1, Canada.

74. Alberta Children’s Hospital Research Institute, University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.

75. Institute of Ecology and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH8 9XP, UK.

76. Gene Bank of Primates and Primate Genetics Laboratory, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany.

77. Department of Genetics, Yale School of Medicine, New Haven, CT 06520, USA.

78. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.

79. Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

80. Toyota Technological Institute at Chicago, Chicago, IL 60637, USA.

Abstract

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.abn8197

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