Long-Read Sequencing Identifies Structural Variants That Alter Gene Expression In Diverse Mice


Varun Moser

Document Type


Publication Date

Summer 2021

JAX Location

In: Student Reports, Summer 2021, The Jackson Laboratory


Structural Variants (SVs) are large genomic regions (≥50 bp) that vary between two different genomes. SVs are implicated in phenotypic differences between individuals and multiple diseases. Through long-read high throughput sequencing (HTS), we have assembled a high-quality set of SVs identified in 14 diverse strains of mice. These include the 8 founders of the Collaborative Cross, a widely utilized panel of recombinant, inbred mouse strains. In the study, we identified putative high-impact SVs using Variant Effect Predictor, and then validate the presence of these SVs in-vitro with PCR and gel electrophoresis. We then identified SVs that were associated with changes in gene expression between mouse strains using RNA sequencing data. We found that of the 30 SVs we PCR validated, 15 were associated with changes in differential gene expression. Additionally, 16 of the SVs showed presence of transposable element (TE) insertions. We found that 8 of the SVs associated with changes in differential gene expression were composed of transposable elements, and we further investigated one SV to identify and predict possible downstream effects. Our finding show that the presence of TE sequences is a large contributor to SVs that associate with changes in gene expression.

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