Complete genome assemblies of two mouse subspecies reveal structural diversity of telomeres and centromeres
It has been more than 20 years since the publication of the C57BL/6J mouse reference genome, which has been a key catalyst for understanding the biology of mammalian diseases. However, the mouse reference genome still lacks telomeres and centromeres, contains 281 chromosomal sequence gaps and only partially represents many biomedically relevant loci. Here we present the first telomere-to-telomere (T2T) mouse genomes for two key inbred strains, C57BL/6J and CAST/EiJ. These T2T genomes reveal substantial variability in telomere and centromere sizes and structural organization. We thus add an additional 213 Mb of new sequence to the reference genome, which contains 517 protein-coding genes. We also examined two important but incomplete loci in the mouse genome-the pseudoautosomal region (PAR) on the sex chromosomes and KRAB zinc-finger protein loci. We identified distant locations of the PAR boundary, different copy numbers and sizes of segmental duplications and a multitude of amino acid substitution mutations in PAR genes.
Authors
- Tianzhen Wu (ORCID: https://orcid.org/0009-0006-0821-6000)
- Jingtao Lilue (ORCID: https://orcid.org/0000-0002-1958-0231)
- Mohab Helmy (ORCID: https://orcid.org/0000-0003-2830-499X)
- Kevin R Costello (ORCID: https://orcid.org/0000-0001-6104-0776)
- Landen Gozashti (ORCID: https://orcid.org/0000-0001-6023-3138)
- Iraad F. Bronner
- Laura G. Reinholdt (ORCID: https://orcid.org/0000-0003-4054-4048)
- Takaoki Kasahara (ORCID: https://orcid.org/0000-0002-0953-5146)
- Michael A. Quail (ORCID: https://orcid.org/0000-0002-3861-0483)
- Olivia S. Harringmeyer (ORCID: https://orcid.org/0000-0003-4040-2226)
- Thomas Keane (ORCID: https://orcid.org/0000-0001-7532-6898)
- Katarzyna Marta Zoltowska (ORCID: https://orcid.org/0000-0001-5853-3465)
- Emma Dawson (ORCID: https://orcid.org/0000-0002-6713-6346)
- Anne Czechanski (ORCID: https://orcid.org/0000-0003-3210-4210)
- Anne C. Ferguson‐Smith (ORCID: https://orcid.org/0000-0002-7608-5894)
- Tadafumi Kato (ORCID: https://orcid.org/0000-0001-7856-3952)
- David J. Adams (ORCID: https://orcid.org/0000-0001-9490-0306)
- B. Magnus Francis
Institutions
- Carl von Ossietzky Universität Oldenburg (DE)
- European Bioinformatics Institute (GB)
- Howard Hughes Medical Institute (US)
- University of Nottingham (GB)
- University of Cambridge (GB)
- RIKEN Center for Brain Science (JP)
- The Gurdon Institute (GB)
- Wellcome Sanger Institute (GB)
- Juntendo University (JP)
- Jackson Laboratory (US)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1038/s41588-025-02367-z
- Citations
- 4
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 7.00
Funders
- Wellcome Trust
- European Molecular Biology Laboratory
- Vlaamse regering
- Provincie West-Vlaanderen
- Medical Research Council
- RIKEN