Kenneth J 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: Somatic retrotransposition alters the genetic landscape of the human brain. In: Nature, 479 (7374), pp. 534–537, 2011.

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.

BibTeX (Download)

@article{Baillie2011-cw,
title = {Somatic retrotransposition alters the genetic landscape of the  human brain},
author = {Kenneth J Baillie and Mark W Barnett and Kyle R Upton and Daniel J Gerhardt and Todd A Richmond and Fioravante De Sapio and Paul M Brennan and Patrizia Rizzu and Sarah Smith and Mark Fell and Richard T Talbot and Stefano Gustincich and Thomas C Freeman and John S Mattick and David A Hume and Peter Heutink and Piero Carninci and Jeffrey A Jeddeloh and Geoffrey J Faulkner},
url = {http://dx.doi.org/10.1038/nature10531},
year  = {2011},
date = {2011-10-01},
journal = {Nature},
volume = {479},
number = {7374},
pages = {534--537},
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.},
keywords = {Faulknerlab, Major_Publication},
pubstate = {published},
tppubtype = {article}
}