Mobilizing diversity: transposable element insertions in genetic variation and disease

Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. .
Mobile DNA (Impact Factor: 2.43). 09/2010; 1(1):21. DOI: 10.1186/1759-8753-1-21
Source: PubMed

ABSTRACT 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.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer is the second leading cause of death in women. New therapies have emerged in the last decade that target hormone receptors in breast cancer but despite encouraging results and survi val statistics, breast cancer remains a leading cause of death, mainly due to frequent therapeutic escape or limited treatment options. Thus, it is imperati ve to find new therapeutic strategies to treat breast cancer. It is increasingly evident that the activation of normally silent mutagenic retroelements occurs at an early stage of breast cancer and is significantly associated with lymph node metastasis. Our recent study found that the existing antiretroviral drug, efavirenz, can be used as anticancer agents by inhibiting the activity of tumor-promoting retroelements, leading to a reduction in the rate of cancer proliferation and promoting cancer cell differentiation. Newly emerging data revealed that efavirenz modulates the expression of cellular genes and miRNAs that can restore normal cellular functions. Because it is an existing drug with known safety profiles and pharmacokinetics, this antiretroviral drug coul d be rapi dly utilized for treatment of breast cancer than they originally intended. Cancer Cell & Microenvironment 2014; 1: e319 doi: 10.14800/ccm.319; © 2014 by Danny Rangasamy. Retro elements, including endogenous retroviruses and retrotransposons, are endogenous mobile DNA elements that utilize reverse transcriptase and RNA intermediates to relocate within the genome [1] . Although nearly half of the human genome is made up of retro elements, only a fraction of retro elements is intact and functionally active because of mutations and truncation at their 5'end. Among the retro elements, L1 elements are the largest class of retrotransposons, of which about 80-100 copies present in human cells are classified as highly active or retro transposition competent elements [2]
  • Source
    [Show abstract] [Hide abstract]
    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.
    Molecular Biology and Evolution 03/2015; DOI:10.1093/molbev/msv062 · 14.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the molecular basis of ageing remains a fundamental problem in biology. In multicellular organisms, while the soma undergoes a progressive deterioration over the lifespan, the germ line is essentially immortal as it interconnects the subsequent generations. Genomic instability in somatic cells increases with age, and accumulating evidence indicates that the disintegration of somatic genomes is accompanied by the mobilisation of transposable elements (TEs) that, when mobilised, can be mutagenic by disrupting coding or regulatory sequences. In contrast, TEs are effectively silenced in the germ line by the Piwi-piRNA system. Here, we propose that TE repression transmits the persistent proliferation capacity and the non-ageing phenotype (e.g., preservation of genomic integrity) of the germ line. The Piwi-piRNA pathway also operates in tumorous cells and in somatic cells of certain organisms, including hydras, which likewise exhibit immortality. However, in somatic cells lacking the Piwi-piRNA pathway, gradual chromatin decondensation increasingly allows the mobilisation of TEs as the organism ages. This can explain why the mortality rate rises exponentially throughout the adult life in most animal species, including humans.
    Cellular and Molecular Life Sciences CMLS 04/2015; 72(10). DOI:10.1007/s00018-015-1896-0 · 5.86 Impact Factor

Preview (2 Sources)

Available from