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Transposable elements occur more frequently in autism-risk genes: Implications for the role of genomic instability in autism

Translational Neuroscience volume 4, pages 172–202 (2013)Cite this article

Abstract

An extremely large number of genes have been associated with autism. The functions of these genes span numerous domains and prove challenging in the search for commonalities underlying the conditions. In this study, we instead looked at characteristics of the genes themselves, specifically in the nature of their transposable element content. Utilizing available sequence databases, we compared occurrence of transposons in autismrisk genes to randomized controls and found that transposable content was significantly greater in our autism group. These results suggest a relationship between transposable element content and autism-risk genes and have implications for the stability of those genomic regions.

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References

  1. Kazazian H.H.Jr., Mobile DNA: Finding treasure in junk, FT Press Science, New Jersey, 2011

    Google Scholar 

  2. Tassabehji M., Strachan T., Anderson M., Campbell R.D., Collier S., Lako M., Identification of a novel family of human endogenous retroviruses and characterization of one family member, HERV-k(C4), located in the complement C4 gene cluster, Nucleic Acids Res., 1991, 22, 5211–5217

    Article  Google Scholar 

  3. Xu L.M., Li J.R., Huang Y., Zhao M., Tang X., Wei L., AutismKB: an evidence-based knowledgebase of autism genetics, Nucleic Acids Res., 2012, 40, D1016–D1022

    PubMed  Article  CAS  Google Scholar 

  4. Pinto D., Pagnamenta A.T., Keli L., Anney R., Merico D., Regan R., et al., Functional impact of global rare copy number variation in autism spectrum disorder, Nature, 2010, 466, 368–372

    PubMed  Article  CAS  Google Scholar 

  5. Shlien A., Tabori U., Marshall C.R., Pienkowska M., Feuk L., Novokmet A., et al., Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome, Proc. Natl. Acad. Sci. USA, 2008, 105, 11264–11269

    PubMed  Article  CAS  Google Scholar 

  6. Verkerk A.J., Pieretti M., Sutcliffe J.S., Fu Y.H., Kuhl D.P., Pizzuti A., et al., Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome, Cell, 1991, 65, 905–914

    PubMed  Article  CAS  Google Scholar 

  7. Liu Y., Hock J. M., Van Beneden R. J., Li X., Aberrant overexpression of FOXM1 transcription factor plays a critical role in lung carcinogenesis induced by low doses of arsenic, Mol. Carcinogen., 2012, Epub ahead of print, doi: 10.1002/mc.21989

    Google Scholar 

  8. Schmidt J. M., Good R.T., Appleton B., Sherrard H., Raymant G.C., Bogwitz M.R., et al., Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus, PLoS Genet., 2010, 6, e1000998

    PubMed  Article  Google Scholar 

  9. McGinnis W., Shermoen A.W., Beckendorf S.K., A transposable element inserted just 5’ to a Drosophila glue protein gene alters gene expression and chromatin structure, Cell, 1983, 34, 75–84

    PubMed  Article  CAS  Google Scholar 

  10. Hoffman-Liebermann B., Liebermann D., Troutt A., Kedes L.H., Cohen S.N., Human homologs of TU transposon sequences: polypurine/polypyrimidine sequence elements that can alter DNA conformation in vitro and in vivo, Mol. Cell. Biol., 1986, 6, 3622–3642

    Google Scholar 

  11. Hedges D.J., Deininger P.L., Inviting instability: transposable elements, double-strand breaks, and the maintenance of genome integrity, Mutat. Res., 2007, 616, 46–59

    PubMed  Article  CAS  Google Scholar 

  12. Thomas-Chollier M., Sand O., Turatsinze J.V., Janky R., Defrance M., Vervisch E., et al., RSAT: regulatory sequence analysis tools, Nucleic Acids Res., 2008, 36, W119–W127

    PubMed  Article  CAS  Google Scholar 

  13. Flicek P., Amode M.R., Barrell D., Beal K., Brent S., Carvalho-Silva D., et al., Ensembl 2012., Nucleic Acids Res., 2012, 40, D84–D90

    PubMed  Article  CAS  Google Scholar 

  14. Levy A., Sela N., Ast G., TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates, Nucleic Acids Res., 2008, 36, D47-D52

  15. International Schizophrenia Consortium, Rare chromosomal deletions and duplications increase risk of schizophrenia, Nature, 2008, 455, 237–241

    Article  Google Scholar 

  16. Shlien A., Malkin D., Copy number variations and cancer, Genome Med., 2009, 1, 62

    PubMed  Article  Google Scholar 

  17. Cross-Disorder Group of the Psychiatric Genomics Consortium, Smoller J.W., Craddock N., Kendler K., Lee P.H., Naele B.M., et al., Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis, Lancet, 2013, 381, 1372-1379

  18. Girirajan S., Dennis M.Y., Baker C., Malig M., Coe B.P., Campbell C.D., et al., Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder, Am. J. Hum. Genet., 2013, 92, 221–237

    PubMed  Article  CAS  Google Scholar 

  19. Millan M. J., An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy, Neuropharmacology, 2012, 68, 2–82

    PubMed  Article  Google Scholar 

  20. Shulha H.P., Cheung I., Whittle C., Wang J., Virgil D., Lin C.L., et al., Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons, Arch. Gen. Psychiat., 2012, 69, 314–324

    PubMed  Article  CAS  Google Scholar 

  21. Yuan J., Pu M., Zhang Z., Lou Z., Histone H3-K56 acetylation is important for genomic stability in mammals, Cell Cycle, 2009, 8, 1747–1753

    PubMed  Article  CAS  Google Scholar 

  22. Slotkin R. K., Martienssen R., Transposable elements and the epigenetic regulation of the genome, Nat. Rev. Genet., 2007, 8, 272–285

    PubMed  Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky, USA

    Emily L. Williams, Hong Li & Mengsheng Qiu

  2. Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, Kentucky, USA

    Manuel F. Casanova & Andrew E. Switala

Authors
  1. Emily L. Williams
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  2. Manuel F. Casanova
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  3. Andrew E. Switala
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  4. Hong Li
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  5. Mengsheng Qiu
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Corresponding author

Correspondence to Emily L. Williams.

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Williams, E.L., Casanova, M.F., Switala, A.E. et al. Transposable elements occur more frequently in autism-risk genes: Implications for the role of genomic instability in autism. Translat.Neurosci. 4, 172–202 (2013). https://doi.org/10.2478/s13380-013-0113-6

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  • DOI: https://doi.org/10.2478/s13380-013-0113-6

Keywords

  • Autism-risk genes
  • Autism spectrum disorders
  • Genomic instability
  • Transposons