Translational Neuroscience

, Volume 4, Issue 2, pp 172–202 | Cite as

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

  • Emily L. WilliamsEmail author
  • Manuel F. Casanova
  • Andrew E. Switala
  • Hong Li
  • Mengsheng Qiu
Research Article


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.


Autism-risk genes Autism spectrum disorders Genomic instability Transposons 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Kazazian H.H.Jr., Mobile DNA: Finding treasure in junk, FT Press Science, New Jersey, 2011Google Scholar
  2. [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, 5211–5217CrossRefGoogle Scholar
  3. [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–D1022PubMedCrossRefGoogle Scholar
  4. [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, 368–372PubMedCrossRefGoogle Scholar
  5. [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, 11264–11269PubMedCrossRefGoogle Scholar
  6. [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, 905–914PubMedCrossRefGoogle Scholar
  7. [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.21989Google Scholar
  8. [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, e1000998PubMedCrossRefGoogle Scholar
  9. [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, 75–84PubMedCrossRefGoogle Scholar
  10. [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, 3622–3642Google Scholar
  11. [11]
    Hedges D.J., Deininger P.L., Inviting instability: transposable elements, double-strand breaks, and the maintenance of genome integrity, Mutat. Res., 2007, 616, 46–59PubMedCrossRefGoogle Scholar
  12. [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–W127PubMedCrossRefGoogle Scholar
  13. [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–D90PubMedCrossRefGoogle Scholar
  14. [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-D52Google Scholar
  15. [15]
    International Schizophrenia Consortium, Rare chromosomal deletions and duplications increase risk of schizophrenia, Nature, 2008, 455, 237–241CrossRefGoogle Scholar
  16. [16]
    Shlien A., Malkin D., Copy number variations and cancer, Genome Med., 2009, 1, 62PubMedCrossRefGoogle Scholar
  17. [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, 1372-1379Google Scholar
  18. [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, 221–237PubMedCrossRefGoogle Scholar
  19. [19]
    Millan M. J., An epigenetic framework for neurodevelopmental disorders: from pathogenesis to potential therapy, Neuropharmacology, 2012, 68, 2–82PubMedCrossRefGoogle Scholar
  20. [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, 314–324PubMedCrossRefGoogle Scholar
  21. [21]
    Yuan J., Pu M., Zhang Z., Lou Z., Histone H3-K56 acetylation is important for genomic stability in mammals, Cell Cycle, 2009, 8, 1747–1753PubMedCrossRefGoogle Scholar
  22. [22]
    Slotkin R. K., Martienssen R., Transposable elements and the epigenetic regulation of the genome, Nat. Rev. Genet., 2007, 8, 272–285PubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Wien 2013

Authors and Affiliations

  • Emily L. Williams
    • 1
    Email author
  • Manuel F. Casanova
    • 2
  • Andrew E. Switala
    • 2
  • Hong Li
    • 1
  • Mengsheng Qiu
    • 1
  1. 1.Department of Anatomical Sciences and NeurobiologyUniversity of Louisville School of MedicineLouisvilleUSA
  2. 2.Department of Psychiatry and Behavioral SciencesUniversity of Louisville School of MedicineLouisvilleUSA

Personalised recommendations