Document Type

Article

Publication Date

11-19-2022

Publication Title

Nat Commun

Keywords

JGM, Humans, DNA Transposable Elements, Genome, Human, Gene Rearrangement, DNA Copy Number Variations, Tripartite Motif Proteins, Ubiquitin-Protein Ligases

JAX Source

Nat Commun. 2022;13(1):7115

Volume

13

Issue

1

First Page

7115

Last Page

7115

ISSN

2041-1723

PMID

36402840

DOI

https://doi.org/10.1038/s41467-022-34810-8

Grant

This work was supported in part by the National Institutes of Health grants R00GM120453 and R35GM133600 from the NIGMS, P30CA034196 from the NCI, and startup funds from the University of Connecticut Health and The Jackson Laboratory to Christine R. Beck.

Abstract

Transposable elements constitute about half of human genomes, and their role in generating human variation through retrotransposition is broadly studied and appreciated. Structural variants mediated by transposons, which we call transposable element-mediated rearrangements (TEMRs), are less well studied, and the mechanisms leading to their formation as well as their broader impact on human diversity are poorly understood. Here, we identify 493 unique TEMRs across the genomes of three individuals. While homology directed repair is the dominant driver of TEMRs, our sequence-resolved TEMR resource allows us to identify complex inversion breakpoints, triplications or other high copy number polymorphisms, and additional complexities. TEMRs are enriched in genic loci and can create potentially important risk alleles such as a deletion in TRIM65, a known cancer biomarker and therapeutic target. These findings expand our understanding of this important class of structural variation, the mechanisms responsible for their formation, and establish them as an important driver of human diversity.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

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