Somatic retrotransposition alters the genetic landscape of the human brain
By J. Baillie, M. Barnett, K. Upton, D. J. Gerhardt, Todd A. Richmond, Fioravante De Sapio, Paul M. Brennan, P. Rizzu, Sarah Smith, M. Fell and 9 more. Nature, 2011
694 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Plant Science
View Paper: https://www.semanticscholar.org/paper/6f6246809c19f888b185c84a5c7d87eb4f8c488d
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Genetics
In Molecular Biology
- Kevin V. Morris
- John S. Mattick
- Philipp Kapranov
- Marcel E. Dinger
- Howard Y. Chang
- Igor V. Makunin
- Debashish Chowdhury
- Tim R. Mercer
In Plant Science
Citations in the corpus
- Transposition Driven Genomic Heterogeneity in the Drosophila Brain: A Dissertation (2012, neutral): “2 Several reports have indicated that specific regions of the mammalian brain, most evidently the hippocampus, might be particularly predisposed to LINE-1 (L1) element retrotransposition (Coufal et al., 2009; Baillie et al., 2011).”
- The rise of regulatory RNA (2014, background): “…and snoRNA-derived small RNAs, the roles of piRNAs in retrotransposon dynamics and the remodelling of the genome by retrotransposons in the brain 114 , the mechanisms and extent of RNA-mediated trans-generational epigenetic inheritance 342 , the locations of RNA binding sites (RNA-DNA duplexes…”
- Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use (2016, background): “some alter the genetic landscape of the human brain (203,204), another has influenced maize domestication (205) and many are important in genome dynamics and evolution.”