Resolution of structural variation in diverse mouse genomes reveals chromatin remodeling due to transposable elements.

Authors

Ardian Ferraj, The Jackson LaboratoryFollow
Peter A Audano, The Jackson LaboratoryFollow
Parithi Balachandran, The Jackson LaboratoryFollow
Anne M Czechanski, The Jackson LaboratoryFollow
Jacob I Flores, The Jackson Laboratory
Alexander A Radecki, The Jackson Laboratory
Varun Mosur, The Jackson Laboratory
David S Gordon
Isha A Walawalkar, The Jackson LaboratoryFollow
Evan E Eichler
Laura G ReinholdtFollow
Christine R Beck, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

5-10-2023

Original Citation

Ferraj A, Audano P, Balachandran P, Czechanski A, Flores J, Radecki A, Mosur V, Gordon D, Walawalkar I, Eichler E, Reinholdt L, Beck C. Resolution of structural variation in diverse mouse genomes reveals chromatin remodeling due to transposable elements. Cell Genom. 2023;3(5):100291.

Keywords

JGM, JMG, SS1

JAX Source

Cell Genom. 2023;3(5):100291.

ISSN

2666-979X

PMID

37228752

DOI

https://doi.org/10.1016/j.xgen.2023.100291

Abstract

Diverse inbred mouse strains are important biomedical research models, yet genome characterization of many strains is fundamentally lacking in comparison with humans. In particular, catalogs of structural vari- ants (SVs) (variants R 50 bp) are incomplete, limiting the discovery of causative alleles for phenotypic vari- ation. Here, we resolve genome-wide SVs in 20 genetically distinct inbred mice with long-read sequencing. We report 413,758 site-specific SVs affecting 13% (356 Mbp) of the mouse reference assembly, including 510 previously unannotated coding variants. We substantially improve the Mus musculus transposable element (TE) callset, and we find that TEs comprise 39% of SVs and account for 75% of altered bases. We further utilize this callset to investigate how TE heterogeneity affects mouse embryonic stem cells and find multiple TE classes that influence chromatin accessibility. Our work provides a comprehensive analysis of SVs found in diverse mouse genomes and illustrates the role of TEs in epigenetic differences.

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).