The Deep Genome Project

K C Kent Lloyd¹, David J Adams², Gareth Baynam^{3

4

5}, Arthur L Beaudet⁶, Fatima Bosch⁷, Kym M Boycott⁸, Robert E Braun⁹, Mark Caulfield¹⁰, Ronald Cohn¹¹, Mary E Dickinson^{6

12}, Michael S Dobbie¹³, Ann M Flenniken¹⁴, Paul Flicek¹⁵, Sanjeev Galande¹⁶, Xiang Gao¹⁷, Anne Grobler¹⁸, Jason D Heaney⁶, Yann Herault¹⁹, Martin Hrabě de Angelis^{20

21

22}, James R Lupski⁶, Stanislas Lyonnet²³, Ann-Marie Mallon²⁴, Fabio Mammano²⁵, Calum A MacRae²⁶, Roderick McInnes²⁷, Colin McKerlie^{11

28}, Terrence F Meehan¹⁵, Stephen A Murray⁹, Lauryl M J Nutter²⁸, Yuichi Obata²⁹, Helen Parkinson¹⁶, Michael S Pepper³⁰, Radislav Sedlacek³¹, Je Kyung Seong³², Toshihiko Shiroishi²⁹, Damian Smedley³³, Glauco Tocchini-Valentini²⁵, David Valle³⁴, Chi-Kuang Leo Wang³⁵, Sara Wells²⁴, Jacqueline White⁹, Wolfgang Wurst^{36

37

38}, Ying Xu³⁹, Steve D M Brown⁴⁰

Affiliations

¹ Department of Surgery, School of Medicine, and Mouse Biology Program, University of California, Davis, CA, 95618, USA. KCLloyd@ucdavis.edu.
² Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
³ Western Australian Register of Developmental Anomalies and Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, Australia.
⁴ Division of Paediatrics and Telethon Kids Institute, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.
⁵ Faculty of Science and Engineering, School of Spatial Sciences, Curtin University, Perth, Australia.
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
⁷ Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma Barcelona, Barcelona, Spain.
⁸ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, K1H 8L1, Canada.
⁹ The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
¹⁰ Genomics England, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
¹¹ The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
¹² Departments of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
¹³ Phenomics Australia, The Australian National University, 131 Garran Road, Acton, ACT, 2601, Australia.
¹⁴ The Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Toronto, ON, M5T 3H7, Canada.
¹⁵ European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
¹⁶ National Facility for Gene Function in Health and Disease, Department of Biology, Indian Institute of Science, Education and Research (IISER) Pune, Pune, Maharashtra, 411008, India.
¹⁷ SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, 210061, China.
¹⁸ DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, 2520, South Africa.
¹⁹ Université de Strasbourg, CNRS, INSERM, Institut de Génétique, Biologie Moléculaire et Cellulaire, Institut Clinique de la Souris, IGBMC, PHENOMIN-ICS, 67404, Illkirch, France.
²⁰ German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
²¹ Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85354, Freising-Weihenstephan, Germany.
²² German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
²³ Institut Imagine, UMR-1163 INSERM et Université de Paris, Hôpital Universitaire Necker-Enfants Malades, 24, Boulevard du Montparnasse, 75015, Paris, France.
²⁴ Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
²⁵ Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Biochemistry and Cell Biology (IBBC), Monterotondo Scalo, I-00015, Rome, Italy.
²⁶ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
²⁷ Lady Davis Research Institute, Jewish General Hospital, McGill University, 3999 Côte Ste- Catherine Road, Montreal, Quebec, H3T 1E2, Canada.
²⁸ The Centre for Phenogenomics, The Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.
²⁹ RIKEN BioResource Research Center, Tsukuba, Ibaraki, 305-0074, Japan.
³⁰ Institute for Cellular and Molecular Medicine, Department Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
³¹ Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, 252 50, Vestec, Czech Republic.
³² Korea Mouse Phenotyping Consortium (KMPC) and BK21 Program for Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
³³ Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
³⁴ McKusick-Nathans Department of Genetic Medicine, The Johns Hopkins University School of Medicine, 519 BRB, 733 N Broadway, Baltimore, MD, 21205, USA.
³⁵ National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan.
³⁶ Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764, Neuherberg, Germany.
³⁷ Chair of Developmental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85354, Freising-Weihenstephan, Germany.
³⁸ Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig Maximillian's Universitat Munchen, 81377, Munich, Germany.
³⁹ Cambridge-Suda Genomic Resource Center, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China.
⁴⁰ Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK. s.brown@har.mrc.ac.uk.

PMID: 32008577
PMCID: PMC6996159
DOI: 10.1186/s13059-020-1931-9

Editorial

The Deep Genome Project

K C Kent Lloyd et al. Genome Biol. 2020.

. 2020 Feb 3;21(1):18.

doi: 10.1186/s13059-020-1931-9.

Authors

Affiliations

¹ Department of Surgery, School of Medicine, and Mouse Biology Program, University of California, Davis, CA, 95618, USA. KCLloyd@ucdavis.edu.
² Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
³ Western Australian Register of Developmental Anomalies and Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, Australia.
⁴ Division of Paediatrics and Telethon Kids Institute, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.
⁵ Faculty of Science and Engineering, School of Spatial Sciences, Curtin University, Perth, Australia.
⁶ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.
⁷ Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma Barcelona, Barcelona, Spain.
⁸ Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, K1H 8L1, Canada.
⁹ The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
¹⁰ Genomics England, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
¹¹ The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
¹² Departments of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
¹³ Phenomics Australia, The Australian National University, 131 Garran Road, Acton, ACT, 2601, Australia.
¹⁴ The Centre for Phenogenomics, Lunenfeld-Tanenbaum Research Institute, Toronto, ON, M5T 3H7, Canada.
¹⁵ European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
¹⁶ National Facility for Gene Function in Health and Disease, Department of Biology, Indian Institute of Science, Education and Research (IISER) Pune, Pune, Maharashtra, 411008, India.
¹⁷ SKL of Pharmaceutical Biotechnology and Model Animal Research Center, Collaborative Innovation Center for Genetics and Development, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, 210061, China.
¹⁸ DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, 2520, South Africa.
¹⁹ Université de Strasbourg, CNRS, INSERM, Institut de Génétique, Biologie Moléculaire et Cellulaire, Institut Clinique de la Souris, IGBMC, PHENOMIN-ICS, 67404, Illkirch, France.
²⁰ German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
²¹ Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85354, Freising-Weihenstephan, Germany.
²² German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany.
²³ Institut Imagine, UMR-1163 INSERM et Université de Paris, Hôpital Universitaire Necker-Enfants Malades, 24, Boulevard du Montparnasse, 75015, Paris, France.
²⁴ Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK.
²⁵ Monterotondo Mouse Clinic, Italian National Research Council (CNR), Institute of Biochemistry and Cell Biology (IBBC), Monterotondo Scalo, I-00015, Rome, Italy.
²⁶ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
²⁷ Lady Davis Research Institute, Jewish General Hospital, McGill University, 3999 Côte Ste- Catherine Road, Montreal, Quebec, H3T 1E2, Canada.
²⁸ The Centre for Phenogenomics, The Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.
²⁹ RIKEN BioResource Research Center, Tsukuba, Ibaraki, 305-0074, Japan.
³⁰ Institute for Cellular and Molecular Medicine, Department Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
³¹ Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, 252 50, Vestec, Czech Republic.
³² Korea Mouse Phenotyping Consortium (KMPC) and BK21 Program for Veterinary Science, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
³³ Clinical Pharmacology, William Harvey Research Institute, School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
³⁴ McKusick-Nathans Department of Genetic Medicine, The Johns Hopkins University School of Medicine, 519 BRB, 733 N Broadway, Baltimore, MD, 21205, USA.
³⁵ National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan.
³⁶ Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764, Neuherberg, Germany.
³⁷ Chair of Developmental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85354, Freising-Weihenstephan, Germany.
³⁸ Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig Maximillian's Universitat Munchen, 81377, Munich, Germany.
³⁹ Cambridge-Suda Genomic Resource Center, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China.
⁴⁰ Medical Research Council Harwell Institute (Mammalian Genetics Unit and Mary Lyon Centre), Harwell, Oxfordshire, OX11 0RD, UK. s.brown@har.mrc.ac.uk.

PMID: 32008577
PMCID: PMC6996159
DOI: 10.1186/s13059-020-1931-9

No abstract available

PubMed Disclaimer

Conflict of interest statement

PF is a member of the Scientific Advisory Boards of Fabric Genomics, Inc., and Eagle Genomics, Ltd. The other authors declare that they have no competing interests.

Figures

**Fig. 1**
IMPC phenotyping of mouse models of human orthologous genes. *Outer ring:* Of the 22,901 genes in the mouse genome, 18,000 are human orthologs (blue) and 4901 are unique to the mouse (gray). *Inner ring:* There are currently 6255 genes (green) with phenotyping data of null alleles, and another 2925 genes (yellow) will be phenotyped over the next 2 years, leaving ~ 9000 human orthologs (red) with no plans for either production or phenotyping by the IMPC

**Fig. 2**
Proportion of human protein coding genes with known genotype to phenotype associations from human and a fish, rat, worm, mouse, fly, and yeast model organisms or b mouse alone. As described in the text, the depth of phenotypic coverage does not match the breadth of coverage enabled by model organisms. Human phenotypes are taken from known OMIM, Orphanet, and Clinvar Mendelian disease associations

See this image and copyright information in PMC

References

1. Waterston RH, et al. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002;420:520–562. doi: 10.1038/nature01262. - DOI - PubMed
1. Hartley T, et al. The unsolved rare genetic disease atlas? An analysis of the unexplained phenotypic descriptions in OMIM. Am J Med Genet. 2018;178C:458–462. doi: 10.1002/ajmg.c.31662. - DOI - PubMed
1. Posey JE, et al. Insights into genetics, human biology and disease gleaned from family based genomic studies. Genetics Med. 2019;21:798–812. doi: 10.1038/s41436-018-0408-7. - DOI - PMC - PubMed
1. Brommage Robert, Powell David R., Vogel Peter. Predicting human disease mutations and identifying drug targets from mouse gene knockout phenotyping campaigns. Disease Models & Mechanisms. 2019;12(5):dmm038224. doi: 10.1242/dmm.038224. - DOI - PMC - PubMed
1. Mungall CJ, et al. The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species. Nucleic Acids Res. 2017;45:D712–D722. doi: 10.1093/nar/gkw1128. - DOI - PMC - PubMed

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The Deep Genome Project

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The Deep Genome Project

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Conflict of interest statement

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