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Genomic Structural Variants in Nervous System Disorders pp 197–227Cite as

Locus-Specific DNA Methylation Profiling of Human LINE-1 Retrotransposons

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Part of the book series: Neuromethods ((NM,volume 182))

Abstract

Long Interspersed Element 1 (LINE-1 or L1) retrotransposons are the only active and autonomous mobile genetic elements present in the human genome. They are responsible for insertional mutagenesis traced to the germline and early embryo, cancer cells and healthy somatic tissues, such as the brain. L1 insertions can therefore impact both the heritable and somatic genome, with the potential to lead to pathogenesis in either context. The mobility of any given L1 copy is highly dependent on its ability to escape epigenetic repression and be transcribed to produce the intermediary RNA necessary for retrotransposition. L1 transcription is typically driven by an internal promoter encoded within the L1 5′ untranslated region, which contains a CpG island that is in turn subject to epigenetic silencing mediated by DNA methylation. In each of us, there are ~350 transcriptional units of the most recent (and potentially mobile) L1s, with many of these only being found in small human populations. In certain cell types, such as neurons, somatic L1 insertions can arise and incorporate new L1 transcriptional units. The technique presented here allows en masse DNA methylation profiling of multiple L1s in a manner allowing locus-specific resolution of individual L1 copies escaping repression in the brain, other healthy tissues, cancer biopsies, and cultured neural cells, among others.

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Acknowledgments

F.J.S-L. acknowledges the support of the Fundación Pública Andaluza “Progreso y Salud” and the Junta de Andalucía EMERGIA Grant (20_00225). M.H.C.K acknowledges the support of the College of Medicine and Veterinary Medicine (University of Edinburgh). G.J.F. acknowledges the support of a CSL Centenary Fellowship, an NHMRC Investigator Grant (GNT1173711), and the Mater Foundation.

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Authors and Affiliations

  1. GENYO, Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research, PTS Granada, Granada, Spain

    Francisco J. Sanchez-Luque

  2. MRC Human Genetics Unit, Institute of Genetics and Cancer (IGC), University of Edinburgh, Western General Hospital Campus, Edinburgh, UK

    Francisco J. Sanchez-Luque & Marie-Jeanne H. C. Kempen

  3. Mater Research Institute, University of Queensland, Woolloongabba, QLD, Australia

    Geoffrey J. Faulkner

  4. Queensland Brain Institute, University of Queensland, St. Lucia, QLD, Australia

    Geoffrey J. Faulkner

  5. Institute of Parasitology and Biomedicine Lopez-Neyra, Spanish National Research Council (CSIC), PTS Granada, Granada, Spain

    Francisco J. Sanchez-Luque

Authors
  1. Francisco J. Sanchez-Luque
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  2. Marie-Jeanne H. C. Kempen
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  3. Geoffrey J. Faulkner
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Corresponding author

Correspondence to Francisco J. Sanchez-Luque .

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Editors and Affiliations

  1. Queen Square Institute of Neurology, University College London, London, UK

    Christos Proukakis

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Sanchez-Luque, F.J., Kempen, MJ.H.C., Faulkner, G.J. (2022). Locus-Specific DNA Methylation Profiling of Human LINE-1 Retrotransposons. In: Proukakis, C. (eds) Genomic Structural Variants in Nervous System Disorders. Neuromethods, vol 182. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2357-2_11

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  • DOI: https://doi.org/10.1007/978-1-0716-2357-2_11

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2356-5

  • Online ISBN: 978-1-0716-2357-2

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