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.
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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}
}