Segmental duplication-mediated rearrangements alter the landscape of mouse genomes

Segmental duplications (SDs) are dynamic regions of mammalian genomes that drive structural variation and phenotypic diversity. However, genome-wide characterization of the SD landscape and the rearrangements mediated by SD paralogs in mouse genomes has been limited by the near-exclusive reliance on short-read sequencing technologies. Here, we integrate long-read genome assemblies, optical mapping, and k-mer based copy number analysis across eight genetically diverse inbred mouse strains to identify and characterize SD-mediated rearrangements. We identify 223 rearrangements affecting over 14 Mb of sequence and reveal substantial variation in gene content. These rearrangements affect loci involved in immunity, sensory perception, and gene regulation, including variation in the amylase gene cluster (Amy2a) and KRAB-zinc finger genes. We observed that SD flanks in mouse genomes are significantly enriched for young LINE-1 transposable elements, suggesting a potential role for transposons in promoting recombination and generating SDs within mice. Our findings highlight the contribution of SDs to genome structure and intra-species variation, and provide a resource for identifying regions prone to rearrangement in a critical model organism for biomedical research.