A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

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Summary

The seventh iteration of the reference genome assembly for Rattus norvegicus—mRatBN7.2—corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

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Highlights

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mRatBN7.2 is a rat reference genome with improved contiguity and accuracy
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Gene annotations, from both RefSeq and Ensembl, are improved with mRatBN7.2
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Our analysis of 120 strains/substrains of rats found 20 million sequence variations
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A refined phylogenetic tree reveals the relationships between laboratory rats

Abstract

de Jong et al. evaluated the seventh assembly of the rat reference genome, mRatBN7.2, and found that it reduces base-level errors and increases contiguity, although some misassemblies remain. Gene annotations are now more complete. Analysis of whole genomes representing 120 rat strains/substrains revealed 20 million sequence variations. Phylogenetic analysis refined ancestral relationships among these strains. In addition, a new rat genetic map, along with annotated transcription start sites and alternative polyadenylation sites based on mRatBN7.2, is provided.

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Most cited references 103

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Author and article information

Contributors

Jun Z. Li

Hao Chen

Journal

Journal ID (nlm-ta): Cell Genom

Journal ID (iso-abbrev): Cell Genom

Title: Cell Genomics

Publisher: Elsevier

ISSN (Electronic): 2666-979X

Publication date PMC-release: 26 March 2024

Publication date Collection: 10 April 2024

Publication date (Electronic): 26 March 2024

Volume: 4

Issue: 4

Electronic Location Identifier: 100527

Affiliations

[1 ]Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center, Memphis, TN, USA

[2 ]Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA

[3 ]Institute of Biotechnology, University of Helsinki, Helsinki, Finland

[4 ]Department of Psychiatry, University of California San Diego, San Diego, CA, USA

[5 ]Department of Integrative Structural and Computational Biology, Scripps Research, San Diego, CA, USA

[6 ]Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

[7 ]Rat Genome Database, Medical College of Wisconsin, Milwaukee, WI, USA

[8 ]Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA

[9 ]Department of Medicine, University of California San Diego, San Diego, CA, USA

[10 ]Tree of Life, Wellcome Sanger Institute, Cambridge, UK

[11 ]Institute of Genetics and Biophysics, National Research Council, Naples, Italy

[12 ]Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA

[13 ]Department of Anatomy, Physiology & Genetics, The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

[14 ]The Brown Foundation Institute of Molecular Medicine, Center for Human Genetics, University of Texas Health Science Center, Houston, TX, USA

[15 ]Genome Structure and Ageing, University of Groningen, UMC, Groningen, the Netherlands

[16 ]European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus in Hinxton, Cambridgeshire, UK

[17 ]Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Louisville, KY, USA

[18 ]Center for Proteomics and Metabolomics, St. Jude Children’s Research Hospital, Memphis, TN, USA

[19 ]Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

[20 ]Center for Immunity and Immunotherapies, Seattle Children’s Research Institute, Seattle, WA, USA

[21 ]Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA

[22 ]Institute of Physiology, Czech Academy of Sciences, Prague, Czechia

[23 ]Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

[24 ]Department of Animal Sciences, Washington State University, Pullman, WA, USA

[25 ]National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA

[26 ]Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA

Author notes

[∗ ]Corresponding author junzli@ 123456med.umich.edu

[∗∗ ]Corresponding author hchen@ 123456uthsc.edu

[27]

These authors contributed equally

[28]

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Article

Publisher Item ID: S2666-979X(24)00069-7 Publisher ID: 100527

DOI: 10.1016/j.xgen.2024.100527

PMC ID: 11019364

PubMed ID: 38537634

SO-VID: d6cd0e72-8303-4664-9084-8d9d8cad043e

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 2 October 2023

Date revision received : 26 December 2023

Date accepted : 29 February 2024

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

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Animal models of intrauterine growth restriction (IUGR)

Most cited references 103

STAR: ultrafast universal RNA-seq aligner.

Basic local alignment search tool.

PLINK: a tool set for whole-genome association and population-based linkage analyses.

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