O'Donnell, K. A. & Burns, K. H. Mobilizing diversity: transposable element insertions in genetic variation and disease. Mob. DNA 1, 21

Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. .
Mobile DNA (Impact Factor: 2.11). 09/2010; 1(1):21. DOI: 10.1186/1759-8753-1-21
Source: PubMed


Transposable elements (TEs) comprise a large fraction of mammalian genomes. A number of these elements are actively jumping in our genomes today. As a consequence, these insertions provide a source of genetic variation and, in rare cases, these events cause mutations that lead to disease. Yet, the extent to which these elements impact their host genomes is not completely understood. This review will summarize our current understanding of the mechanisms underlying transposon regulation and the contribution of TE insertions to genetic diversity in the germline and in somatic cells. Finally, traditional methods and emerging technologies for identifying transposon insertions will be considered.

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    • "For over 100 million years, Long Interspersed Nuclear Elements 1 (known as LINE-1 or L1), from the L1 clade, have sculpted Metatheria and Eutheria genomes, representing between 15 to 20% of the DNA, while being almost absent in Prototheria genomes (Smit 1996; Lander et al. 2001; Lindblad-Toh et al. 2005; Mandal and Kazazian 2008; Warren et al. 2008). In the human genome, L1 is believed to be the only autonomous mobile element remaining active, and it continues to have a mutagenic impact by various mechanisms including insertion, duplication, deletion and recombination (Deininger et al. 2003; Chen et al. 2005; Babushok and Kazazian 2007; Jurka et al. 2007; Muotri et al. 2007; Cordaux and Batzer 2009; Xing et al. 2009; Beck et al. 2010; Ewing and Kazazian 2010; Huang et al. 2010; Iskow et al. 2010; O'Donnell and Burns 2010; Baillie et al. 2011). Although never observed, HERV-K, an LTR retrotransposon, may theoretically be active since functional copies have the potential to exist in individual genomes (Dewannieux et al. 2006; Ruprecht et al. 2008; Hohn et al. 2013). "
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    ABSTRACT: Transposable elements comprise more than 45% of the human genome and LINE-1 (L1) is the only autonomous mobile element remaining active. Since its identification, it has been proposed that L1 contributes to the mobilization and amplification of other cellular RNAs and more recently, experimental demonstrations of this function has been described for many transcripts such as Alu, a non-autonomous mobile element, cellular mRNAs or small non-coding RNAs. Detailed examination of the mobilization of various cellular RNAs revealed distinct pathways by which they could be recruited during retrotransposition; template choice or template switching. Here, by analysing genomic structures and retrotransposition signatures associated to small nuclear RNA (snRNA) sequences, we identified distinct recruiting steps during the L1 retrotransposition cycle for the formation of snRNA-processed pseudogenes. Interestingly, some of the identified recruiting steps take place in the nucleus. Moreover, after comparison to other vertebrate genomes, we established that snRNA amplification by template switching is common to many LINE families from several LINE clades. Finally, we suggest that U6 snRNA copies can serve as markers of L1 retrotransposition dynamics in mammalian genomes. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Full-text · Article · Mar 2015 · Molecular Biology and Evolution
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    • "Furthermore, some of the recent integrated TEs are capable of producing new copies in the human genome. These de novo TE insertions have the potential to cause a genomic difference among human populations and even human individuals, which could be related to human phenotypes and diseases [20]. "
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    ABSTRACT: Since the advent of whole-genome sequencing, transposable elements (TEs), just thought to be 'junk' DNA, have been noticed because of their numerous copies in various eukaryotic genomes. Many studies about TEs have been conducted to discover their functions in their host genomes. Based on the results of those studies, it has been generally accepted that they have a function to cause genomic and genetic variations. However, their infinite functions are not fully elucidated. Through various mechanisms, including de novo TE insertions, TE insertion-mediated deletions, and recombination events, they manipulate their host genomes. In this review, we focus on Alu, L1, human endogenous retrovirus, and short interspersed element/variable number of tandem repeats/Alu (SVA) elements and discuss how they have affected primate genomes, especially the human and chimpanzee genomes, since their divergence.
    Full-text · Article · Dec 2012
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    • "Furthermore, large-scale studies have expanded the pool of human disorders resulting from retrotransposon-mediated insertional mutagenesis. Recent reviews have discussed the technical aspects of these new methods [5-8]. We focus here on the known, as well as inferred, potential health impact of their novel findings. "
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    ABSTRACT: Perhaps as much as two-thirds of the mammalian genome is composed of mobile genetic elements ('jumping genes'), a fraction of which is still active or can be reactivated. By their sheer number and mobility, retrotransposons, DNA transposons and endogenous retroviruses have shaped our genotype and phenotype both on an evolutionary scale and on an individual level. Notably, at least the non-long terminal repeat retrotransposons are still able to cause disease by insertional mutagenesis, recombination, providing enzymatic activities for other mobile DNA, and perhaps by transcriptional overactivation and epigenetic effects. Currently, there are nearly 100 examples of known retroelement insertions that cause disease. In this review, we highlight those genome-scale technologies that have expanded our knowledge of the diseases that these mobile elements can elicit, and we discuss the potential impact of these findings for medicine. It is now likely that at least some types of cancer and neurological disorders arise as a result of retrotransposon mutagenesis.
    Full-text · Article · Feb 2012 · Genome Medicine
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