Publication Date:
2011-11-01
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224101/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224101/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- 090385/Wellcome Trust/United Kingdom -- 090385/Z/09/Z/Wellcome Trust/United Kingdom -- BB/H005935/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2011 Oct 30;479(7374):534-7. doi: 10.1038/nature10531.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22037309" target="_blank"〉PubMed〈/a〉
Keywords:
Alu Elements/genetics
;
Base Sequence/genetics
;
Brain/*metabolism
;
Caudate Nucleus/metabolism
;
Clonal Evolution/genetics
;
DNA Copy Number Variations/genetics
;
Epistasis, Genetic
;
Genome, Human/genetics
;
Germ-Line Mutation/*genetics
;
Hippocampus/metabolism
;
Histone Deacetylase 1/genetics
;
Humans
;
Mosaicism
;
Mutagenesis, Insertional/*genetics
;
Nerve Tissue Proteins/genetics
;
Organ Specificity/genetics
;
Polymerase Chain Reaction
;
Retroelements/*genetics
;
Transcription Factors/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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