High-quality mouse reference genomes reveal the structural complexity of the murine protein-coding landscape
We present a collection of 17 high-quality long-read inbred mouse strain genomes with complete annotation (contig N50s of 0.8-33.9 Mbp). This collection includes 12 widely used classical laboratory strains and 5 wild-derived strains. We have resolved previously incomplete genomic regions, including the major histocompatibility complex (MHC), defensin cluster, T cell receptor, and Ly49 complexes. Hundreds of non-reference genes from previous publications not found in GRCm39, such as Defa1, Raet1a, and Klra20 (Ly49T), were localized in the new reference genomes. We conducted a genome-wide scan of variable number tandem repeats (VNTRs) within the coding regions, identifying over 400 genes with VNTR polymorphisms with up to 600 repeat copies and repeat units reaching 990 nucleotides. Our strain-specific annotations enhance RNA sequencing (RNA-seq) analyses, as demonstrated in PWK/PhJ, where we observed a 5.1% improvement in read mapping and expression-level differences in 2.1% of coding genes compared to using GRCm39.
Authors
- Tianzhen Wu (ORCID: https://orcid.org/0009-0006-0821-6000)
- Swati Sinha (ORCID: https://orcid.org/0000-0002-1027-9856)
- Jingtao Lilue (ORCID: https://orcid.org/0000-0002-1958-0231)
- Mohab Helmy (ORCID: https://orcid.org/0000-0003-2830-499X)
- Jonathan M. D. Wood (ORCID: https://orcid.org/0000-0002-7545-2162)
- Erik Garrison (ORCID: https://orcid.org/0000-0003-3821-631X)
- Alexandra Sapetschnig
- Dan Zhou (ORCID: https://orcid.org/0000-0001-9300-4366)
- Marco Túlio Pardini Gontijo (ORCID: https://orcid.org/0000-0001-6605-3402)
- Laura G. Reinholdt (ORCID: https://orcid.org/0000-0003-4054-4048)
- Édith Heard (ORCID: https://orcid.org/0000-0001-8052-7117)
- Eric A. Miska (ORCID: https://orcid.org/0000-0002-4450-576X)
- Rachel K. Meade (ORCID: https://orcid.org/0000-0002-8322-0257)
- Andrea Guarracino (ORCID: https://orcid.org/0000-0001-9744-131X)
- Patrick B. Chen (ORCID: https://orcid.org/0000-0002-2460-690X)
- Leanne S. Haggerty (ORCID: https://orcid.org/0000-0001-8843-3596)
- Francesca Floriana Tricomi (ORCID: https://orcid.org/0000-0002-6170-5499)
- Tomás Di Domenico (ORCID: https://orcid.org/0000-0003-2887-815X)
- Kerstin Howe (ORCID: https://orcid.org/0000-0003-2237-513X)
- Runjia Qu
- Thomas Keane (ORCID: https://orcid.org/0000-0001-7532-6898)
- Diandian Sun
- Isabell Rall (ORCID: https://orcid.org/0000-0001-5911-4609)
- Clare M. Smith (ORCID: https://orcid.org/0000-0003-2601-0955)
- Jonathan Flint
- Navin B. Ramakrishna (ORCID: https://orcid.org/0000-0003-2974-9886)
- Anne Czechanski (ORCID: https://orcid.org/0000-0003-3210-4210)
- Fergal J. Martin (ORCID: https://orcid.org/0000-0002-1672-050X)
- Narendra Kumar Meena (ORCID: https://orcid.org/0000-0001-9903-1824)
- Jin Li (ORCID: https://orcid.org/0000-0001-9201-2321)
- David J. Adams (ORCID: https://orcid.org/0000-0001-9490-0306)
- Xiaomin Yan (ORCID: https://orcid.org/0000-0001-7937-1733)
- Elizabeth Anderson
Institutions
- European Bioinformatics Institute (GB)
- Central South University (CN)
- University of Tennessee Health Science Center (US)
- University of California, Los Angeles (US)
- Duke University (US)
- Wenzhou Medical University (CN)
- The Gurdon Institute (GB)
- Wellcome Sanger Institute (GB)
- Spanish National Cancer Research Centre (ES)
- Jackson Laboratory (US)
- European Molecular Biology Laboratory (DE)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1016/j.xgen.2025.101074
- Primary Topic
- Genomics and Phylogenetic Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fulbright Association
- European Molecular Biology Laboratory
- National Institutes of Health
- Medical Research Council