Interchromosomal translocation in neural progenitor cells exposed to L1 retrotransposition

LINE-1 (L1) elements are a class of transposons, comprising approximately 19% and 21% of the mouse and human genomes, respectively. L1 retrotransposons can reverse transcribe their own RNA sequence into a de novo DNA copy integrated into a new genomic location. This activity, known as retrotransposi...

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Published inGenetics and molecular biology Vol. 46; no. 1; p. e20220268
Main Author Muotri, Alysson R
Format Journal Article
LanguageEnglish
Portuguese
Published Brazil Sociedade Brasileira de Genética 01.01.2023
Subjects
BIOCHEMISTRY & MOLECULAR BIOLOGY
brain mosaicism
Cellular, Molecular and Developmental Genetics
GENETICS & HEREDITY
L1 retrotransposition
neural progenitor cells
translocations
translocations
brain mosaicism
L1 retrotransposition
neural progenitor cells
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Summary:LINE-1 (L1) elements are a class of transposons, comprising approximately 19% and 21% of the mouse and human genomes, respectively. L1 retrotransposons can reverse transcribe their own RNA sequence into a de novo DNA copy integrated into a new genomic location. This activity, known as retrotransposition, may induce genomic alterations, such as insertions and deletions. Interestingly, L1s can retrotranspose and generate more de novo L1 copies in brains than in other somatic tissues. Here, we describe for the first time interchromosomal translocation triggered by ectopic L1 retrotransposition in neural progenitor cells. Such an observation adds to the studies in neurological and psychiatric diseases that exhibited variation in L1 activity between diseased brains compared with controls, suggesting that L1 activity could be detrimental when de-regulated.
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Associate Editor: Carlos F. M. Menck
Conflict of Interest: ARM is a co-founder and has an equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis, focusing on therapeutic applications customized for autism spectrum disorders and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, following its conflict of interest policies.
Author Contribution: All the experiments were designed, performed, and interpreted by ARM.
ISSN:1415-4757
1678-4685
1678-4685
DOI:10.1590/1678-4685-gmb-2022-0268