Somatic retrotransposition alters the genetic landscape of the human brain View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-11

AUTHORS

J. Kenneth Baillie, Mark W. Barnett, Kyle R. Upton, Daniel J. Gerhardt, Todd A. Richmond, Fioravante De Sapio, Paul M. Brennan, Patrizia Rizzu, Sarah Smith, Mark Fell, Richard T. Talbot, Stefano Gustincich, Thomas C. Freeman, John S. Mattick, David A. Hume, Peter Heutink, Piero Carninci, Jeffrey A. Jeddeloh, Geoffrey J. Faulkner

ABSTRACT

Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes. More... »

PAGES

534

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature10531

DOI

http://dx.doi.org/10.1038/nature10531

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022999884

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22037309


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