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Center director: Prof. Niels Tommerup tommerup@imbg.ku.dk

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| Hans-Hilger Ropers, Vera Kalscheuer; from Max Planck Institute for Molecular Genetics, Berlin, Germany |
| Disease-associated balanced chromosome rearrangements |
| Mental retardation is present in 2 to 3 percent of the population, either as an isolated finding or as part of a syndrome or broader disorder. Causes of MR are numerous and include genetic and environmental factors. Identification of families with mentally retarded males has led to the mapping and cloning of a number of X-linked recessive loci and relevant genes for mental retardation. However, there has been little progress in the identification of autosomal genes for mental retardation. In collaboration with the Mendelian Cytogenetic Network and many associated laboratories, we systematically investigate autosomal and X;autosomal translocations. Molecular cytogenetic analysis of the breakpoints is a prerequisite for the identification of disrupted genes and disturbed gene regulation |
| Poul Jennum, Stine Knudsen; from Søvnlaboratoriet, Klinisk neurofysiologisk afdeling, KAS Glostrup, Denmark |
| Sleep disorders and genetics |
In the project we search for genetic causes of sleep disorders by molecular cytogenetic and DNA array screening of patients with balanced chromosomal rearrangements identified in Mendelian Cytogenetics Network database (MCNdb) (http://www.mcndb.org). We have identified two balanced translocations associated with sleep disturbances, including one with a breakpoint within a region where association studies have suggested a candidate locus.
By molecular mapping of the involved chromosomal breakpoints we will identify and characterize novel candidate genes for abnormal sleep |
| Christian Pilebæk Hansen, lægelig direktør; from The Danish Epilepsy Centre, Dianalund, Denmark |
| Epilepsy and Genetics |
| The Danish Epilepsy Centre, Dianalund specializes in the treatment of epilepsy in patients referred from all regions of Denmark and the Faroe Islands. In the project Epilepsy and Genetics we search for novel genetic causes of various forms of epilepsy (complex partial epilepsy; juvenile myoclonic epilepsy; epilepsy associated with specific congenital brain malformations) |
| Inger Kjær, Dorrit Nolting; from Odontologisk Institut |
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| By combining the expertice of Dorrit Nolting in histology and histochemistry with the expertice of WJC in DNA, RNA and LNA based in situ hybridization, we have established a joint laboratory for tissue in situ hybridization. In collaboration with Sakari Kauppinen and Asli Silahtoroglu from WJC and the group of Ronald Plasterk, Utrecht, The Netherlands, the laboratory establish a murine expression atlas of microRNA genes. Together with ph.d.-students at WJC, the laboratory establish the expression patterns of selected candidate disease genes identified from cloned translocation breakpoints.
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| Teit Johansen from NsGene A/S |
| Gene expression and neurological/neuro-developmental disorders |
| NsGene A/S is a privately held Danish biotechnology company dedicated to developing cell and gene-based therapies for the treatment of CNS disorders. From well-dissected human fetal neural tissues, NsGene and its academic partners are applying GeneChip® technology to generate a gene expression database of 39,000 genes expressed during human central nervous system development. Differentially expressed genes from this database will be cross-referenced with known loci and translocation breakpoints associated with neurological and neuro-developmental disorders |
| Elena Grigorenko from Yale University |
| A IARU research collaboration on the genetics of dyslexia |
| Wilhelm Johannsen Centre for Functional Genome Research has initiated a collaboration with Dr. Elena Grigorenko at Child Study Center, Yale University, with the aim to identify genetic factors involved in dyslexia. By linkage analysis the Yale group has pointed to several chromosomal regions that may harbour genetic factors involved in dyslexia. By combining these data with translocations that have been identified in Danish individuals with dyslexia, we aim to identify some of these dyslexia genes. This study is a collaboration between two scientific groups from members of the International Alliance of Research Universities (IARU) |
| Network Coordinator Dr. Andreas Ladurner from European Molecular Biology Laboratory (EMBL) |
| The Marie Curie Research Training Network "Chromatin Plasticity" |
The Marie Curie Research Training Network Chromatin Plasticity aims to reveal novel mechanisms in the regulation of chromatin structure and to prepare the next generation of European scientists to the highest standards.
Our overall scientific objective is to understand chromatin plasticity. Specifically, we will study chromatin modifications, nuclear architecture, cell-fate decisions, targeted recombination, centromere function, non-coding siRNA/miRNA transcripts in mammalian epigenetics, alternative splicing and chromatin structure, and a histone variant that binds NAD metabolites. The complexity and novelty of the underlying molecular events, combined with rapid specialization in the field, call for a collaborative endeavor using complementary in vitro and in vivo approaches. Our innovative and interdisciplinary network will integrate distinct approaches (structural biology, biophysics, mouse genetics, cell biology, immunology, molecular biology, high-resolution microscopy and bioinformatics) to examine fundamental epigenetic processes and their links to human disease and therapy.
The Chromatin Plasticity network will examine these mechanisms in mammalian chromatin and disease, focusing on six areas of research:
* Role of non-coding RNAs in mammalian heterochromatin
* Regulation of human chromatin by metabolites
* Chromatin regulation during lymphoid development
* Epigenetic control of lineage decisions by transcriptional regulators
* Development of ChIP-on-Chip data analysis tools and best practice
* Novel tools and therapies for the epigenetic regulation of human disease
In addition to our specific scientific goals, we will implement a comprehensive plan for scientific and career development through collaborative exchanges, training visits, by sharing and joint development of expertise, tools and reagents, and through focused scientific workshops and career development meetings. In doing so, the network will provide wide-ranging opportunities contributing to the development of the next generation of European researchers and life science employees |
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