A Murine Database of Structural Variants Enables the Genetic Architecture of a Spontaneous Murine Lymphoma to be Characterized

A more complete map of the pattern of genetic variation among inbred mouse strains is essential for characterizing the genetic architecture of the many available mouse genetic models of important biomedical traits. Although structural variants (SVs) are a major component of genetic variation, they have not been adequately characterized among inbred strains due to methodological limitations. To address this, we generated high-quality long-read sequencing data for 40 inbred strains; and designed a pipeline to optimally identify and validate different types of SVs. This generated a database for 40 inbred strains with 573,191SVs, which included 10,815 duplications and 2,115 inversions, which also has 70 million SNPs and 7.5 million insertions/deletions. Analysis of this SV database identified an SV that is one component of a bi-genic model for lymphoma susceptibility in SJL mice, which provides mechanistic insight into the genetic basis for susceptibility to murine (and potentially human) lymphomas.