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

被引：27

作者：

Ferraj, Ardian ^{[1
,2
]}

Audano, Peter A. ^{[2
]}

Balachandran, Parithi ^{[2
]}

Czechanski, Anne ^{[3
]}

Flores, Jacob I. ^{[2
]}

Radecki, Alexander A. ^{[1
,2
]}

Mosur, Varun ^{[2
]}

Gordon, David S. ^{[4
,5
]}

Walawalkar, Isha A. ^{[1
,2
]}

Eichler, Evan E. ^{[4
,5
]}

Reinholdt, Laura G. ^{[3
]}

Beck, Christine R. ^{[1
,2
,6
]}

机构：

[1] Univ Connecticut, Hlth Ctr, Dept Genet & Genome Sci, Farmington, CT 06032 USA

[2] Jackson Lab Genom Med, Farmington, CT 06032 USA

[3] Jackson Lab, Bar Harbor, ME 04609 USA

[4] Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA

[5] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA

[6] Univ Connecticut, Inst Syst Genom, Storrs, CT 06269 USA

来源：

CELL GENOMICS | 2023年 / 3卷 / 05期

基金：

美国国家卫生研究院;

关键词：

COLLABORATIVE CROSS; GENETIC-VARIATION; SYSTEMS GENETICS; MUS-MUSCULUS; RETROTRANSPOSITION; IDENTIFICATION; RESOURCE; SEQUENCE; STERILITY; EFFICIENT;

D O I：

10.1016/j.xgen.2023.100291

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：22

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