Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Understanding schizophrenia: the role of LINE-1 retrotransposition in disease aetiology (#512)

Marie-Jeanne H.C. Kempen 1 , Gabriela-Oana Bodea 1 , Sandra Richardson 1 , Francisco Sanchez Luque 1 2 , Chunyu Liu 3 , Elliot Gershon 3 , Geoffrey J. Faulkner 1 4
  1. Mater Research Institute - University of Queensland, Brisbane, QLD, Australia
  2. Pfizer-Universidad de Granada-Junta de Andalucia Centre for Genomics and Oncological Research (Genyo). P.T. Ciencias de la Salud, Granada, Spain
  3. Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, Illinois, USA
  4. Queensland Brain Institute - University of Queensland, St. Lucia, Queensland, Australia

Long interspersed nuclear element 1 (LINE-1 or L1) is an autonomous retrotransposon that uses a “copy and paste” mechanism to retrotranspose in mammalian genomes. L1 makes up ~17% of the human genome and occur most frequently in the brain. L1 mobilization has the potential to impact the genome structure and alter gene activity. Environmental factors, including stress, were found to enhance L1 activity, suggesting a potential role for L1 in the pathophysiology of disorders in which gene-environment interactions play a major role such as Schizophrenia (SCZ). Recently, Bundo et al. (2014) found an increased copy number variation (CNV) of L1 in the cortex of SCZ patients, compared to controls, as well as in the cortex of two animal models of SCZ. However, the mechanism and extent of L1 mobilization impacting the SCZ phenotype remains largely unexplored. The present study aims to deepen our understanding of how L1 contributes to the SCZ using cutting edge genomics and molecular biology approaches. Firstly, human SCZ and control samples were subjected to retrotransposon capture sequencing, a novel high-throughput sequencing approach, to identify the genomic location and structural characteristics of L1 insertions.  Using this technique, we were able to distinguish putative somatic, polymorphic and fixed L1 insertions. Further, we analysed the L1 content of different brain regions by means of qPCR L1 CNV assay in a SCZ mouse model which recapitulates the influence of environmental factors, such as viral infection, in utero on SCZ development. Developmental timing of in utero exposure to such environmental factors has been shown to differentially impact SCZ symptoms. We are currently investigating whether the established distinction in SCZ phenotype can be related to changes in L1 levels. In this way we aim to shed more light on the involvement of L1 in the development of SCZ symptoms.