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A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes

H. Toh, C. Yang, View ORCID ProfileG. Formenti, K. Raja, L. Yan, A. Tracey, W. Chow, K. Howe, L.A. Bergeron, G. Zhang, B. Haase, J. Mountcastle, View ORCID ProfileO. Fedrigo, J. Fogg, B. Kirilenko, C. Munegowda, M. Hiller, A. Jain, D. Kihara, A. Rhie, A.M. Phillippy, S. Swanson, P. Jiang, D.O. Clegg, E.D. Jarvis, J.A. Thomson, R. Stewart, M.J.P. Chaisson, View ORCID ProfileY.V. Bukhman
doi: https://doi.org/10.1101/2021.12.08.471837
H. Toh
22Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93117, USA
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C. Yang
24BGI-Shenzhen, Shenzhen 518083, China
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G. Formenti
8Laboratory of Neurogenetics of Language, The Rockefeller University/HHMI, New York, NY, USA
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  • ORCID record for G. Formenti
K. Raja
2Bioinformatics and Regenerative Biology, Morgridge Institute for Research, Madison, WI, USA
18Sema4, Stamford, CT, USA
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L. Yan
23Department of Psychology & Neuroscience Program, Michigan State University, East Lansing, MI, USA
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A. Tracey
4Tree of Life, Wellcome Sanger Institute, Cambridge CB10 1SA, UK
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W. Chow
4Tree of Life, Wellcome Sanger Institute, Cambridge CB10 1SA, UK
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K. Howe
4Tree of Life, Wellcome Sanger Institute, Cambridge CB10 1SA, UK
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L.A. Bergeron
1Villum Centre for Biodiversity Genomics, Section for Ecology and Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark
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G. Zhang
25Villum Centre for Biodiversity Genomics, Section for Ecology and Evolution
26Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark
24BGI-Shenzhen, Shenzhen 518083, China
27State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
28Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China
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B. Haase
6Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA
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J. Mountcastle
6Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA
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O. Fedrigo
6Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA
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J. Fogg
7Department of Statistics, University of Wisconsin - Madison, Madison, WI, USA
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B. Kirilenko
9LOEWE Centre for Translational Biodiversity Genomics, Senckenberganlage 25, 60325 Frankfurt, Germany
10Senckenberg Research Institute, Senckenberganlage 25, 60325 Frankfurt, Germany
11Goethe-University, Faculty of Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany
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C. Munegowda
9LOEWE Centre for Translational Biodiversity Genomics, Senckenberganlage 25, 60325 Frankfurt, Germany
10Senckenberg Research Institute, Senckenberganlage 25, 60325 Frankfurt, Germany
11Goethe-University, Faculty of Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany
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M. Hiller
9LOEWE Centre for Translational Biodiversity Genomics, Senckenberganlage 25, 60325 Frankfurt, Germany
10Senckenberg Research Institute, Senckenberganlage 25, 60325 Frankfurt, Germany
11Goethe-University, Faculty of Biosciences, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany
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A. Jain
12Department of Computer Science, Purdue University, West Lafayette, IN, USA
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D. Kihara
16Department of Biological Sciences; Purdue University, West Lafayette, IN, USA
12Department of Computer Science, Purdue University, West Lafayette, IN, USA
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A. Rhie
17Genome Informatics Section, National Human Genome Research Institute, Bethesda, MD, USA
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A.M. Phillippy
17Genome Informatics Section, National Human Genome Research Institute, Bethesda, MD, USA
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S. Swanson
2Bioinformatics and Regenerative Biology, Morgridge Institute for Research, Madison, WI, USA
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P. Jiang
14Center for Gene Regulation in Health and Disease (GRHD); Cleveland State University, 2121 Euclid Ave, Cleveland, OH, USA
15Department of Biological, Geological and Environmental Sciences, Cleveland State University, 2121 Euclid Ave, Cleveland, OH, USA
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D.O. Clegg
5Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, Mail Code 5060, University of California, Santa Barbara, CA 93016, USA
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E.D. Jarvis
13The Rockefeller University, Box 54, 1230 York Avenue, New York, New York 10065, USA
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J.A. Thomson
19Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106, USA
20Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA
21Regenerative Biology Laboratory, Morgridge Institute for Research, Madison, WI 53715, USA
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  • For correspondence: ybukhman@morgridge.org
R. Stewart
2Bioinformatics and Regenerative Biology, Morgridge Institute for Research, Madison, WI, USA
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  • For correspondence: ybukhman@morgridge.org
M.J.P. Chaisson
3Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA
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  • For correspondence: ybukhman@morgridge.org
Y.V. Bukhman
2Bioinformatics and Regenerative Biology, Morgridge Institute for Research, Madison, WI, USA
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  • ORCID record for Y.V. Bukhman
  • For correspondence: ybukhman@morgridge.org
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Abstract

The Nile rat (Avicanthis niloticus) is an important animal model for biomedical research, including the study of diurnal rhythms and type 2 diabetes. Here, we report a 2.5 Gb, chromosome-level reference genome assembly with fully resolved parental haplotypes, generated with the Vertebrate Genomes Project (VGP). The assembly is highly contiguous, with contig N50 of 11.1 Mb, scaffold N50 of 83 Mb, and 95.2% of the sequence assigned to chromosomes. We used a novel workflow to identify 3,613 segmental duplications and quantify duplicated genes. Comparative analyses revealed unique genomic features of the Nile rat, including those that affect genes associated with type 2 diabetes and metabolic dysfunctions. These include 14 genes that are heterozygous in the Nile rat or highly diverged from the house mouse. Our findings reflect the exceptional level of genomic detail present in this assembly, which will greatly expand the potential of the Nile rat as a model organism for genetic studies.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://doi.org/10.17605/OSF.IO/J97KC

  • https://www.ncbi.nlm.nih.gov/bioproject/632612

  • https://vgp.github.io/genomeark/Arvicanthis_niloticus/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes
H. Toh, C. Yang, G. Formenti, K. Raja, L. Yan, A. Tracey, W. Chow, K. Howe, L.A. Bergeron, G. Zhang, B. Haase, J. Mountcastle, O. Fedrigo, J. Fogg, B. Kirilenko, C. Munegowda, M. Hiller, A. Jain, D. Kihara, A. Rhie, A.M. Phillippy, S. Swanson, P. Jiang, D.O. Clegg, E.D. Jarvis, J.A. Thomson, R. Stewart, M.J.P. Chaisson, Y.V. Bukhman
bioRxiv 2021.12.08.471837; doi: https://doi.org/10.1101/2021.12.08.471837
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A haplotype-resolved genome assembly of the Nile rat facilitates exploration of the genetic basis of diabetes
H. Toh, C. Yang, G. Formenti, K. Raja, L. Yan, A. Tracey, W. Chow, K. Howe, L.A. Bergeron, G. Zhang, B. Haase, J. Mountcastle, O. Fedrigo, J. Fogg, B. Kirilenko, C. Munegowda, M. Hiller, A. Jain, D. Kihara, A. Rhie, A.M. Phillippy, S. Swanson, P. Jiang, D.O. Clegg, E.D. Jarvis, J.A. Thomson, R. Stewart, M.J.P. Chaisson, Y.V. Bukhman
bioRxiv 2021.12.08.471837; doi: https://doi.org/10.1101/2021.12.08.471837

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