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

Tristan V de Jong; Yanchao Pan; Pasi Rastas; Daniel Munro; Monika Tutaj; Huda Akil; Chris Benner; Denghui Chen; Apurva S Chitre; William Chow; Vincenza Colonna; Clifton L Dalgard; Wendy M Demos; Peter A Doris; Erik Garrison; Aron M Geurts; Hakan M Gunturkun; Victor Guryev; Thibaut Hourlier; Kerstin Howe; Jun Huang; Ted Kalbfleisch; Panjun Kim; Ling Li; Spencer Mahaffey; Fergal J Martin; Pejman Mohammadi; Ayse Bilge Ozel; Oksana Polesskaya; Michal Pravenec; Pjotr Prins; Jonathan Sebat; Jennifer R Smith; Leah C Solberg Woods; Boris Tabakoff; Alan Tracey; Marcela Uliano-Silva; Flavia Villani; Hongyang Wang; Burt M Sharp; Francesca Telese; Zhihua Jiang; Laura Saba; Xusheng Wang; Terence D Murphy; Abraham A Palmer; Anne E Kwitek; Melinda R Dwinell; Robert W Williams; Jun Z Li; Hao Chen

doi:10.1016/j.xgen.2024.100527

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

Cell Genom. 2024 Apr 10;4(4):100527. doi: 10.1016/j.xgen.2024.100527. Epub 2024 Mar 26.

Authors

Tristan V de Jong¹, Yanchao Pan², Pasi Rastas³, Daniel Munro⁴, Monika Tutaj⁵, Huda Akil⁶, Chris Benner⁷, Denghui Chen⁸, Apurva S Chitre⁸, William Chow⁹, Vincenza Colonna¹⁰, Clifton L Dalgard¹¹, Wendy M Demos⁵, Peter A Doris¹², Erik Garrison¹³, Aron M Geurts¹⁴, Hakan M Gunturkun¹, Victor Guryev¹⁵, Thibaut Hourlier¹⁶, Kerstin Howe⁹, Jun Huang¹, Ted Kalbfleisch¹⁷, Panjun Kim¹³, Ling Li¹⁸, Spencer Mahaffey¹⁹, Fergal J Martin¹⁶, Pejman Mohammadi²⁰, Ayse Bilge Ozel², Oksana Polesskaya⁸, Michal Pravenec²¹, Pjotr Prins¹³, Jonathan Sebat⁸, Jennifer R Smith⁵, Leah C Solberg Woods²², Boris Tabakoff¹⁹, Alan Tracey⁹, Marcela Uliano-Silva⁹, Flavia Villani¹³, Hongyang Wang²³, Burt M Sharp¹³, Francesca Telese⁸, Zhihua Jiang²³, Laura Saba¹⁹, Xusheng Wang¹⁸, Terence D Murphy²⁴, Abraham A Palmer²⁵, Anne E Kwitek⁵, Melinda R Dwinell⁵, Robert W Williams¹³, Jun Z Li²⁶, Hao Chen²⁷

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; Department of Integrative Structural and Computational Biology, Scripps Research, San Diego, CA, USA.
⁵ Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Rat Genome Database, Medical College of Wisconsin, Milwaukee, WI, USA.
⁶ Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Medicine, University of California San Diego, San Diego, CA, USA.
⁸ Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
⁹ Tree of Life, Wellcome Sanger Institute, Cambridge, UK.
¹⁰ Institute of Genetics and Biophysics, National Research Council, Naples, Italy; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.
¹¹ Department of Anatomy, Physiology & Genetics, The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹² The Brown Foundation Institute of Molecular Medicine, Center for Human Genetics, University of Texas Health Science Center, Houston, TX, USA.
¹³ Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.
¹⁴ Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 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 Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA; 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; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
²¹ Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.
²² Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
²³ Department of Animal Sciences, Washington State University, Pullman, WA, USA.
²⁴ National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
²⁵ Department of Psychiatry, University of California San Diego, San Diego, CA, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
²⁶ Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. Electronic address: junzli@med.umich.edu.
²⁷ Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: hchen@uthsc.edu.

Abstract

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.

Keywords: Rnor_6.0; genetic map; heterogeneous stock; hybrid rat diversity panel; inbred strains; mRatBN7.2; phylogenetic tree; rat; recombinant inbred; reference genome.

MeSH terms

Animals
Genetic Variation / genetics
Genome* / genetics
Genomics*
Molecular Sequence Annotation
Rats
Whole Genome Sequencing

Abstract

MeSH terms

Grants and funding