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

• Published in: Cell genomics Vol. 4; no. 4; p. 100527
• Main Authors: de Jong, Tristan V., Pan, Yanchao, Rastas, Pasi, Munro, Daniel, Tutaj, Monika, Akil, Huda, Benner, Chris, Chen, Denghui, Chitre, Apurva S., Chow, William, Colonna, Vincenza, Dalgard, Clifton L., Demos, Wendy M., Doris, Peter A., Garrison, Erik, Geurts, Aron M., Gunturkun, Hakan M., Guryev, Victor, Hourlier, Thibaut, Howe, Kerstin, Huang, Jun, Kalbfleisch, Ted, Kim, Panjun, Li, Ling, Mahaffey, Spencer, Martin, Fergal J., Mohammadi, Pejman, Ozel, Ayse Bilge, Polesskaya, Oksana, Pravenec, Michal, Prins, Pjotr, Sebat, Jonathan, Smith, Jennifer R., Solberg Woods, Leah C., Tabakoff, Boris, Tracey, Alan, Uliano-Silva, Marcela, Villani, Flavia, Wang, Hongyang, Sharp, Burt M., Telese, Francesca, Jiang, Zhihua, Saba, Laura, Wang, Xusheng, Murphy, Terence D., Palmer, Abraham A., Kwitek, Anne E., Dwinell, Melinda R., Williams, Robert W., Li, Jun Z., Chen, Hao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.04.2024; Elsevier
• Subjects: Animals; genetic map; Genetic Variation - genetics; Genome - genetics; Genomics; heterogeneous stock; hybrid rat diversity panel; inbred strains; Molecular Sequence Annotation; mRatBN7.2; phylogenetic tree; rat; Rats; recombinant inbred; reference genome; Resource; Rnor_6.0; Whole Genome Sequencing; Rnor_6.0; phylogenetic tree; recombinant inbred; rat; hybrid rat diversity panel; inbred strains; reference genome; genetic map; heterogeneous stock; mRatBN7.2
• ISSN: 2666-979X; 2666-979X
• DOI: 10.1016/j.xgen.2024.100527

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