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

共 105 条

[61] Allelic heterogeneity in LINE-1 retrotransposition activity [J].

Lutz, SM ;

Vincent, BJ ;

Kazazian, HH ;

Balzer, MA ;

Moran, JV .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (06) :1431-1437

[62] Embryonic stem cell potency fluctuates with endogenous retrovirus activity [J].

Macfarlan, Todd S. ;

Gifford, Wesley D. ;

Driscoll, Shawn ;

Lettieri, Karen ;

Rowe, Helen M. ;

Bonanomi, Dario ;

Firth, Amy ;

Singer, Oded ;

Trono, Didier ;

Pfaff, Samuel L. .

NATURE, 2012, 487 (7405) :57-+

[63] Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons [J].

Maksakova, IA ;

Mager, DL .

JOURNAL OF VIROLOGY, 2005, 79 (22) :13865-13874

[64] Preferential Epigenetic Suppression of the Autonomous MusD over the Nonautonomous ETn Mouse Retrotransposons [J].

Maksakova, Irina A. ;

Zhang, Ying ;

Mager, Dixie L. .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (09) :2456-2468

[65] BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity [J].

Martins, Airton C. ;

Lopez-Granero, Caridad ;

Ferrer, Beatriz ;

Tinkov, Alexey A. ;

Skalny, Anatoly V. ;

Paoliello, Monica M. B. ;

Aschner, Michael .

BIOMOLECULES, 2021, 11 (12)

[66] The Ensembl Variant Effect Predictor [J].

McLaren, William ;

Gil, Laurent ;

Hunt, Sarah E. ;

Riat, Harpreet Singh ;

Ritchie, Graham R. S. ;

Thormann, Anja ;

Flicek, Paul ;

Cunningham, Fiona .

GENOME BIOLOGY, 2016, 17

[67] Tissue-specific usage of transposable element-derived promoters in mouse development [J].

Miao, Benpeng ;

Fu, Shuhua ;

Lyu, Cheng ;

Gontarz, Paul ;

Wang, Ting ;

Zhang, Bo .

GENOME BIOLOGY, 2020, 21 (01)

[68] A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development [J].

Modzelewski, Andrew J. ;

Shao, Wanqing ;

Chen, Jingqi ;

Lee, Angus ;

Qi, Xin ;

Noon, Mackenzie ;

Tjokro, Kristy ;

Sales, Gabriele ;

Biton, Anne ;

Anand, Aparna ;

Speed, Terence P. ;

Xuan, Zhenyu ;

Wang, Ting ;

Risso, Davide ;

He, Lin .

CELL, 2021, 184 (22) :5541-+

[69] Epigenetic inheritance at the agouti locus in the mouse [J].

Morgan, HD ;

Sutherland, HGE ;

Martin, DIK ;

Whitelaw, E .

NATURE GENETICS, 1999, 23 (03) :314-318

[70] The genomic landscape shaped by selection on transposable elements across 18 mouse strains [J].

Nellaker, Christoffer ;

Keane, Thomas M. ;

Yalcin, Binnaz ;

Wong, Kim ;

Agam, Avigail ;

Belgard, T. Grant ;

Flint, Jonathan ;

Adams, David J. ;

Frankel, Wayne N. ;

Ponting, Chris P. .

GENOME BIOLOGY, 2012, 13 (06) :R45

← 2 3 4 5 6 7 8 9 10 11 →