Somatic retrotransposition alters the genetic landscape of the human brain

Baillie, J. Kenneth, Barnett, Mark W., Upton, Kyle R., Gerhardt, Daniel J., Richmond, Todd A., De Sapio, Fioravante, Brennan. Paul M., Rizzu, Patrizia, Smith, Sarah, Fell, Mark, Talbot, Richard T., Gustincich, Stefano, Freeman, Thomas C., Mattick, John S., Hume, David A., Heutink, Peter, Carninci, Piero, Jeddeloh, Jeffrey A. and Faulkner, Geoffrey J. (2011) Somatic retrotransposition alters the genetic landscape of the human brain. Nature, 479 7374: 534-537. doi:10.1038/nature10531

Author Baillie, J. Kenneth
Barnett, Mark W.
Upton, Kyle R.
Gerhardt, Daniel J.
Richmond, Todd A.
De Sapio, Fioravante
Brennan. Paul M.
Rizzu, Patrizia
Smith, Sarah
Fell, Mark
Talbot, Richard T.
Gustincich, Stefano
Freeman, Thomas C.
Mattick, John S.
Hume, David A.
Heutink, Peter
Carninci, Piero
Jeddeloh, Jeffrey A.
Faulkner, Geoffrey J.
Title Somatic retrotransposition alters the genetic landscape of the human brain
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2011-10-30
Year available 2011
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.1038/nature10531
Open Access Status DOI
Volume 479
Issue 7374
Start page 534
End page 537
Total pages 4
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes1. 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 2,3. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells 4,5, excluding early embryo development and some malignancies 6,7. Recent reports of L1 expression 8,9 and copy number variation 10,11 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 090385/Z/09/Z
Institutional Status UQ
Additional Notes Article in press

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
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Created: Thu, 01 Dec 2011, 01:18:43 EST by Susan Allen on behalf of Institute for Molecular Bioscience