Results Genetics of the brain

The key objective of this research team was to uncover the complex etiology of pathological brain dysfunction, for dementia and milder age related cognitive decline, by focusing on genetic mechanisms.


We tackled the tasks related to the work package 1, genetics of healthy and diseased brain. We have focused on methodology development to identify early markers of neurodegeneration with non-invasive tests in order to provide very early diagnostics with focus on Parkinson’s disease. The best test is monitoring the onset and the progress of the disease by searching for marker present in the peripheral blood. We have used two methods developed by RIKEN, namely CAGE (cap-analysis gene expression) and nanoCAGE (a miniaturization of CAGE that works with tiny amount of samples) and have explored the peripheral blood transcriptome from early patients and control, identifying an interesting locus, likely to be an enhancer region that control important neighboring genes. In the process, we have optimized and published a method to increase the reproducibility of the CAGE assay. Since we have noted that noncoding RNAs are involved as early biomarkers and are involved as regulatory molecules in other various biological phenomena, we have also further characterized a class of non-coding RNAs essential for DNA repair (published in Nature) and further identified a large class of non-coding RNAs deriving from retrotransposon elements. We have also provided a broad map of expressed RNA in brain of aging patients and have made this resource public for other users. Altogether, we have deepened our knowledge of noncoding RNA expression in health and diseases, focused on methods towards early diagnostic based on genomics exploration.

  1. L Pardo, P Rizzu, M Francescatto, M Vitezic, G Leday, J Sanchez, A Khamis, H Takahashi, W van den Berg, Y Medvedeva, M van de Wiel, C Daub, P Carninci, P Heutink. Regional differences in gene expression and promoter usage in aged human brains, Neurobiology of Aging, 34(7), 1825-1836 (2013) Jul
  2. D Tang, C Plessy, M Salimullah, A Suzuki, R Calligaris, S Gustincich, P Carninci. Suppression of barcode bias in high-throughput transcriptome analyses utilizing template switching, Nucleic Acids Research, 41, 1-12 (2012) Nov
  3. S Francia, F Michelini, A Saxena, D Tang, MJ De Hoon, A Viviana, M Mione, P Carninci, F d’Adda di Fagagna.
    Site-specific DICER and DROSHA RNA products control the DNA damage response, Nature, 488, 231-235 (2012) Aug

    (Review Articles)

  4. A Saxena, D Tang, P Carninci. piRNAs warrant investigation in Rett Syndrome: An Omics Perspective, Disease Markers, 33, 261-275 (2012) Sep
  5. B Lenhard, A Sandelin, P Carninci. Metazoan promoters: emerging characteristics and insights into transcriptional regulation, Nature Reviews Genetics, 13, 233-245 (2012) Apr
  • Research teams

    To reach its objectives, the BrainTrain research program is composed of 5 scientific Research Teams, see list below, with 3 trainees each.
  • Genetics of the brain

    The increasing prevalence for neurodegenerative disease in our aging population poses a growing problem for healthcare.
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  • The synaptic interactome

    Many brain disorders are to be considered 'synaptic diseases" or 'synaptopathies' and cellular function of synapses.
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  • Functional genomic of the synapse

    The synapse is a specialized structure between two neurons at which basal neuronal communication takes place.
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  • Synaptic plasticity

    In neuropsychiatric disorders associated with reduced cognitive abilities, such as age-related cognitive decline, but also mental retardation, the ability of synapses to alter their strength is strongly affected.
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  • Transmission and behavioral function

    The etiology of many disorders including age-related cognitive decline and neurodegenerative disorders such as dementia and Parkinson’s disease is still poorly understood.
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