SFB 577:  Molecular Basis of Clinical Variability in Mendelian Disorders

• Subject Area: Medicine
• Term: from 2001 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5484647

The Human Genome Project has an enormous impact on nearly all aspects of medicine. This is convincingly illustrated by the logarithmic increase of the number of genes implicated in Mendelian disorders, and by the rapidly growing possibilities for presymptomatic diagnosis. Very often, however, the predictive value of such molecular diagnoses is seriously limited by clinical variability of these disorders. Therefore, both from the scientific and the medical point of view, the analysis of clinical variability in Mendelian disorders with known primary defects is a major challenge. Conceptual and methodological developments such as the introduction of large scale analysis of gene expression and protein profiles, the development of sophisticated methods to generate animal models for almost any monogenic disorder and the availability of the entire genomic sequence of several model organisms have opened up exciting new possibilities for addressing this urgent problem. The collaborative research centre propose here aims to identify genetic factors that modify the manifestation and course of inherited disorders and to shed light on their pathogenesis. As a platform for interaction between theoretically and clinically oriented experts it will bridge the gap between fundamental genome research and health care.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Autophagic degradation of aggregated huntingtin: a systematic investigation of cellular components and potential pathway modifiers (Project Head Wanker, Erich E. )
• A03 - The effect of mutations on proteome networking (Project Heads Klose, Joachim ;  Mao, Lei )
• A04 - Interactome of Golgi proteins related to hereditary disorders of connective tissues (Project Head Kornak, Uwe )
• A05 - Defining the transcription network of thyroid development to identify candidate genes for thyroid dysgenesis. (Project Head Krude, Heiko )
• A06 - Molecular Pathology and Embryology of HOXD and BMP Related Limb Malformations (Project Heads Mundlos, Stefan ;  Seemann, Petra )
• A08 - Analysis of the Receptor Tyrosine Kinase Ror2: A Central Modulator in the Brachydactyly Disease Family (Project Heads Mundlos, Stefan ;  Stricker, Sigmar )
• A09 - Analysis of phenotypic and functional variances of lamin B receptor mutations (Project Head Hoffmann, Katrin )
• A10 - Mental retardation genes and their interaction (Project Heads Kalscheuer, Vera ;  Kuss, Andreas ;  Ropers, Hans Hilger )
• B01 - Nijmegen Breakage Syndrome (NBS): A link between radiosensitivity, chromosomal instability and immunodeficiency (Project Heads Digweed, Martin J. ;  Sperling, Karl )
• B03 - Molecular genetics of obesity: The contribution of POMC and MC4R gene mutations (Project Heads Biebermann, Heike ;  Grüters-Kieslich, Annette )
• B04 - Genetic variability of mitochondrial disorders (Project Head Schülke-Gerstenfeld, Markus )
• B5 - Clinical Variability of Gamma-Thalassemia: Quality Control of Gene Expression by Nonsense mediated Decay (Project Heads Hentze, Matthias ;  Kulozik, Ph.D., Andreas Eckhard )
• C1 - Norrie disease (ND): Molecular Mechanisms of Pathogenesis and Modulation of Disease Serverity (Project Head Berger, Wolfgang )
• C02 - Protein Monoaminylation: Novel regulatory functions of monoaminergic hormones (Project Head Walther, Diego J. )
• C3 - Downstream Effects of MECP1 Mutations in Rett Syndrome and other Forms of X-linked Mental Retardation studied by cDNA Arrays (Project Heads Nuber, Ulrike ;  Ropers, Hans Hilger )
• C04 - Functional Analysis of the MID1 gene product- a Key to an Understanding of the Clinical Variability of Opitz BBB/G Syndrome (Project Head Schweiger, Susann )
• Z1 - DNA Microarry Center (Project Heads Nuber, Ulrike ;  Sperling, Karl )
• Z02 - Core Facility Proteomics, service and collaboration within the SFB (Project Heads Klose, Joachim ;  Mao, Lei ;  Wanker, Erich E. )
• Z04 - Central tasks of the Collaborative Research Centre (Project Heads Mundlos, Stefan ;  Sperling, Karl )
• Z05 - Central Facility for Animal Model Generation and Characterization (Project Heads Mundlos, Stefan ;  Walther, Diego J. )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Co-Applicant Institution: Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating Institution: Max-Delbrück-Centrum für Molekulare Medizin (MDC); Max-Planck-Institut für molekulare Genetik (MPIMG)
• Spokesperson: Professor Dr. Stefan Mundlos