The mouse pangenome reveals the structural complexity of the murine protein coding landscape

Mohab Helmy; Jin U. Li; Xinyu F. Yan; Rachel K. Meade; Elizabeth L. Anderson; Patrick B. Chen; Anne Czechanski; Tomás Di Domenico; Jonathan Flint C; Erik P. Garrison; Marco Túlio Pardini Gontijo; Andrea Guarracino; Leanne S. Haggerty; Édith Heard; Kerstin Howe; Narendra Kumar Meena; Fergal J. Martin; Eric Alexander Miska; Isabell Rall; Navin B. Ramakrishna; Alexandra Sapetschnig; Swati Sinha; Diandian Sun; Francesca Floriana Tricomi; Runjia Qu; Jonathan M. D. Wood; Tianzhen Wu; Dian J. Zhou; Laura G. Reinholdt; David J. Adams

doi:10.1016/j.xgen.2025.101074

GenomicsCell GenomicsDec 1, 2025

Peer-reviewed journal article

The mouse pangenome reveals the structural complexity of the murine protein coding landscape

Mohab Helmy iD, Jin U. Li, Xinyu F. Yan, Rachel K. Meade iD, Elizabeth L. Anderson, Patrick B. Chen iD, Anne Czechanski iD, Tomás Di Domenico iD, Jonathan Flint C iD, Erik P. Garrison iD, Marco Túlio Pardini Gontijo iD, Andrea Guarracino iD, Leanne S. Haggerty iD, Édith Heard iD, Kerstin Howe iD, Narendra Kumar Meena iD, Fergal J. Martin iD, Eric Alexander Miska iD, Isabell Rall iD, Navin B. Ramakrishna iD, Alexandra Sapetschnig iD, Swati Sinha iD, Diandian Sun, Francesca Floriana Tricomi iD, Runjia Qu iD, , Thomas Keane iD

Abstract

We present the first mouse pangenome consisting of 17 high-quality inbred mouse strain genomes with complete annotation. This collection includes 12 widely used classical laboratory strains and 5 wild-derived strains. We have fully resolved previously incomplete genomic regions, including the major histocompatibility complex (MHC), the defensin cluster, T-cell receptor, and Ly49 complexes. Hundreds of non-reference genes identified in previous publications not found in GRCm39, like Defa1, Raet1a, and Klra20 (Ly49T), were localised in the new reference genomes. We conducted the first genome-wide scan of variable number tandem repeats (VNTRs) within the coding regions of mice, identifying over 400 genes with VNTR polymorphisms up to more than 600 repeat copies and repeat units reaching 990 nucleotides. Our strain-specific annotations enhance 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.

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