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Institute of Human Genetics University Hospital Heidelberg Director: Prof. Dr. med. Claus R. Bartram Im Neuenheimer Feld 366, 69120 HEIDELBERG © Medienzentrum UniversitätsKlinikum HD © Medienzentrum UniversitätsKlinikum HD © Medienzentrum UniversitätsKlinikum HD Institute of Human Genetics Organigram Division of Developmental Genetics Research Group Dr. Schneider Prof. Steinbeisser RESEARCH RESEARCH Research Group Dr. Runz Research Group PD Dr. Niesler Institute of Human Genetics Department of Human Molecular Genetics Department of Human Genetics Prof. Bartram Outpatient Clinic Director Prof. Bartram Prof. Rappold Service Sectors PD Dr. Dr. Moog Research Group Dr. Endris LABORATORY DIAGNOSTICS Molecular Genetics Molecular Cytogenetics Cytogenetics Dr. Hinderhofer Prof. Jauch Prof. Janssen Institute of Human Genetics The University of Heidelberg is the oldest in Germany; one of the four founding faculties in 1386 was the Medical Faculty of Heidelberg. The institute represents the field of human genetics in terms of patient care, research and teaching. The two departments of the institute, Human Genetics and Human Molecular Genetics, are composed of several research groups and diagnostic laboratories. Contact Dept. of Human Genetics: Prof. Dr. med. Claus R. Bartram Im Neuenheimer Feld 366, 69120 Heidelberg Fon: +49 (0) 6221 56 51 51 Fax: +49 (0) 6221 56 51 55 [email protected] Outpatient Clinic: PD Dr. Dr. med. Ute Moog Im Neuenheimer Feld 344a, 69120 Heidelberg Fon: +49 (0) 6221 -56 5082 (direct), -56 5087 (office) Fax: +49 (0) 6221 56 5080 [email protected] Over 600 years of education and research in medicine have had multiple implications for our faculty: tradition, experience, and a deep founded responsibility to conquer the incredible challenges that medicine of the 21st century presents. Dept. of Human Molecular Genetics: Prof. Dr. rer. nat. Gudrun Rappold Im Neuenheimer Feld 366, 69120 Heidelberg Fon: +49 (0) 6221 -56 5059 (direct), -56 5153 (office) Fax: +49 (0) 6221 56 51 55 [email protected] Institute of Human Genetics The Institute of Human Genetics was established in 1962 under the direction of Prof. Friedrich Vogel. It is extensively involved in the teaching of students of medicine and biology in Heidelberg, as well as in the specialist training in human genetics. © Medienzentrum UniversitätsKlinikum HD Research activities focus on tumour genetics, developmental genetics as well as on functional gene analysis and neurogenetics. Human genetics is regarded as the prototype of an interdisciplinary specialty designed to function as a bridge between basic research and clinical medicine. With ever increasing rapidity the genetic basis of more and more diseases can be explained and this has led to interchanges with practically all medical fields. The growing need for professional counselling expertise and diagnostic services in the field of medical genetics accounted for the specialist training in human genetics. Quality Assurance Head: Dr. U. Barth To control and maintain our high standards in diagnostic testing the institute has implemented a quality management system. The diagnostic laboratories have been accredited since April 2007 according to DIN EN ISO 15189. © Medienzentrum UniversitätsKlinikum HD Genetic counselling, including inpatient consultations of the Department of Human Genetics, is provided by the Outpatient Clinic. The clinical sector is supported by the diagnostic laboratories for Cytogenetics Molecular Cytogenetics Molecular Genetics To fulfil the requirements of standard and to prove our testing competence internal and external audits are regularly carried out. We also continuously attend in National and European external quality assessment schemes. Genetic Counselling and Laboratory Diagnostics Outpatient Clinic Head: PD Dr. Dr. U. Moog The outpatient clinic of the Institute of Human Genetics offers counselling and diagnostic services for persons with (possibly) genetic disorders. These services are available to both patients of the University Hospital Heidelberg and to those living in this and other regions. Several specialists in clinical genetics, residents in training, social workers and non-medical colleagues are working in the outpatient clinic. tact patient support groups or other counselling services. t Clinical Genetics is a discipline working increasingly in an interdisciplinary setting. For this reason, apart from consultations in the genetic outpatient clinic, multidisciplinary consultations in the Pediatric Department and the Department of Gynaecology of the University Hospital, as well as with several other disciplines working on hereditary tumour syndromes, have been established. In addition, the clinical geneticists of the outpatient clinic serve as consultants in all departments of the University Hospital. The outpatient clinic is open to all persons who possibly are affected by a genetic disease or who are afraid that such disorders may affect their (future) children. In principle, people can address questions regarding every genetic disease to the outpatient clinic. Main efforts and areas of particular clinical expertise are - diagnoses of genetic syndromes and dysmorphology - hereditary tumour-disposition syndromes, e.g. hereditary breast cancer and hereditary colorectal cancer - psychomotor retardation /intellectual disability in children and adults - inborn errors of metabolism - neurological disorders of children and adults - predictive diagnostic testing, e.g. for neurodegenerative diseases - genetics of reproductive medicine - risks during pregnancies and prenatal diagnosis Often questions are asked about very rare disorders of great diversity, for example, rare muscle disorders or metabolic diseases. A visit at the genetic outpatient clinic aims to establish an exact diagnosis by clinical and laboratory investigations, and to provide information about the particular disorder and the recurrence risk. If necessary, we help to con- In addition, special methods are employed for chromosome breakage analysis (e.g. for Fanconi anaemia and Bloom’s syndrome), the establishment of lymphoblastic cell lines (EBV immortalisation), microdissection of chromosomes and DOP-PCR. Laboratory for Molecular Cytogenetics A novel seminar program “Clinical Genetics” has been developed for medical students in their clinical part. Using a broad spectrum of didactic methods, these seminars, together with a clinically oriented main lecture, allow the transfer of well-founded basic knowledge as well as an understanding of the role of genetics in all aspects of modern medicine. Laboratory for Cytogenetics Head: Prof. Dr. J.W.G. Janssen Classical genetics is engaged with the identification of numerical and structural aberrations of prophase and metaphase chromosomes in pre- and postnatal diagnostics and haematopoietic tumours (leukemias). Each year about 2000 patient samples are cytogenetically analysed. We perform chromosome analyses on blood as well as on amnion cells, chorionic villi, cord blood, foetal cells, fibroblasts and bone marrow. Head: Prof. Dr. A. Jauch In addition to conventional cytogenetic methods, fluorescence in situ hybridization (FISH) can be applied for the detection of numerical and structural chromosome aberrations in clinical and tumour diagnostics. FISH allows the visualization of specific chromosomes or chromosomal subregions in individual colours under a fluorescence microscope. The particular advantages of FISH are the high sensitivity (i.e. detection of microdeletion syndromes) as well as the possibility to study chromosomal aberrations directly in interphase nuclei (“interphase cytogenetics“). Genetic Counselling and Laboratory Diagnostics Laboratory for Molecular Diagnostics Hereditary Cancer Predisposition Head: Dr. K. Hinderhofer Dr. Christian Sutter Certain inherited diseases are caused by mutations in the genome. They can be identified by molecular genetic procedures. The Laboratory for Molecular Diagnostics of the Institute of Human Genetics offers molecular genetic testing of numerous diseases. The diagnostic spectrum consist of inherited metabolic diseases; neuropediatric disorders (e.g. fragile X syndrome, Angelman/Prader-Willi syndrome); oncogenetic diseases (e.g. hereditary breast cancer, familial colon cancer); inherited amyloidosis. In addition to testing of hereditary diseases, the laboratory also offers molecular testing of frequent translocations and mutations in leukemic diseases. The directory of tests offered is available on our web page: www.klinikum.uni-heidelberg.de/ Leistungsverzeichnis.112813.0.html?&L=en In a sequencing core (head: Dr. C. Sutter) sequence or fragment analyses are provided inhouse and for the University Hospital using two 16-capillary DNA sequencers. In addition automated Sanger sequencing is carried out at high throughput on a robotic liquid handling platform. Approximately 5% of all cases of breast and ovarian cancer occur on a hereditary basis (Hereditary Breast and Ovarian Cancer). In up to 50% of these cases a causative genetic alteration (mutation) is found in the high risk genes BRCA1 and BRCA2 which is dominantly inherited. Since 1996 we have been offering BRCA1/2 molecular genetic analysis. Not only breast and ovarian cancer but also nearly 5-8% of the bowel cancer cases are inherited. It is 2–5% of these cases that are caused by HNPCC (Hereditary Nonpolyposis Colorectal Cancer) and 0.5-1% by FAP (Familial Adenomatous Polyposis). Both diseases are inherited in a dominant way. Nearly 0.3% of the cases are caused by MAP (MUTYH associated Polyposis) which is recessively inherited. Less than 1% of the cases occur due to rare tumor predisposition syndromes such as Juvenile Polyposis, Peutz-Jeghers-Disease, and Cowden’s disease. Since the end of 2002 we have been offering molecular genetic diagnostics to detect genetic alterations of the APC gene causative for FAP. Since 2003 we have been offering diagnostics regarding alterations of the MUTYH gene (MAP), and since 2008, diagnostics with regard to MLH1 and MSH2 gene mutations which are causative for HNPCC, have been offered as well. Furthermore, we offer a molecular genetic service for Tuberous Sclerosis (TSC), a rare disorder of mostly benign tumors affecting multiple organs even in early childhood. Analyses of the two genes related to the disease, TSC1 and TSC2 have been carried out in our labs since 1996. In addition, since 2006 we have been offering molecular diagnostics of rare endocrine tumor disorders with dominant inheritance (Multiple Endocrine Neoplasia, MEN) such as MEN1 (MEN1 gene) and MEN2 (RET gene). Leukemia, MRD (minimal residual disease) Dr. Rolf Köhler Acute Lymphoblastic Leukemia (ALL) is the most common of childhood malignancies, representing 30 - 35 % of all cases of cancer in children under the age of 15. In about 98% of children affected by this disease, an intensive polychemotherapy treatment, applied over a time period of only 4 weeks, generally leads to a complete remission, with malignant cells falling below the detection limit of conventional diagnostic methods. (< 1-5% maligant cells left in the bone marrow). Assuming a malignant cell population of 1012 by the time of initial diagnosis, a reduction by two orders of magnitude (i.e. 10 -2) means that quite a considerable number of malignant cells, which cannot be identified by means of conventional detection methods, (e.g. morphology, immunophenotyping, cytogenetics and Southern Blot- Analysis) may still remain. The ´Real-Time´ quantitative PCR-Technology (RQ-PCR) results to be a much more sensitive method for detecting minute levels of malignant cells (minimal residual MRD). The identification of suitable DNA markers representing the genetic fingerprinting of leukemic cells, enables us to detect cancer cells among normal lymphocytes at a ratio down to 1 in 10 000 (10-4) or even 1 in a million (10-6). As a marker system we use clone-specific Immunoglobulin (Ig) and T-Cell-Receptor (TCR) gene arrangements, whose probes were designed in a patient and clone-specific way and ideally have a detection limit of ≤ 10-4. Picture: RQ-PCR-Experiments of a Gene-arrangement (by means of a probe with a detection limit of 10-5 and measuring at two different points of time during the +treatment (R1 and R2); MNC (monuclear cell background). The highly sensitive molecular diagnostic evidence of minimal residual disease by means of RQ-PCR (as pictured) is currently the most important histopathological parameter and allows for a precise estimation of an individual risk of recurrence. Based on this information a more adequate treatment regarding the risk of the individual patient is possible. Research Department of Human Molecular Genetics Director: Prof. Dr. G. Rappold The focus of our research interest is on the molecular elucidation of human disease with a special focus on growth and neuronal disorders. To uncover the basic mechanisms on the causes of these disorders, our work employs different cell culture and animal models as well as differentiated stem cells. We would like to understand how mutations correlate with disease, how genes are regulated and how they contribute to differentiation and development. By integrating genetic, molecular, biochemical and cell biological approaches, the basic understanding and function of these proteins and their roles in the relevant networks will be established. Research Projects: Developmental Genes and Growth Factors Project leader: Prof. Dr. G. Rappold Short stature is a growth disorder with often unknown genetic causes. Defects in early developmental genes may be responsible for this kind of growth disorder. The most frequent cause of idiopathic short stature up to date concerns the SHOX gene that we isolated and characterized in our department. Gene defects of the homeobox transcription factor SHOX can be found in syndromal (LériWeill, Langer and Turner syndrome) and nonsyndromal (idiopathic) short stature. At the present time we are analyzing different cell systems and animal models (mouse, frog, chicken) to better understand the function of SHOX during bone development and the exploitation of the molecular signal pathway. The characterization of regulatory processes as well as the identification of different target genes activated by SHOX through si-RNA, microarray and ChIP methods, are topics of thorough research. They are supposed to help us understand the SHOX-dependent early developmental biological processes In the course of an international clinical trial carried out by the company Eli Lilly, we were able to show that SHOX deficiency is a type of short stature which can be treated very well and which was issued the orphan drug status in the United States. We established a central SHOX database here in our institute. Supported by the Deutsche Forschungsgemeinschaft (DFG), our research group is currently analyzing further new candidate genes for infant growth. The Homeobox Gene SHOX 2 Head: Dr. K. Schneider SHOX and SHOX2 are highly homologous genes that belong to a small group of homeobox transcription factors with essential functions during early embryogenesis, especially in limb, heart and brain development. By combining different animal models (transgenic and knock-out mice, frog, zebrafish and chick) as well as cell culture systems (mouse embryonic stem cells, primary chondrocytes and fibroblasts) we investigate the role of SHOX2 during different developmental processes. Insights from our work with the Shox2 knockout mouse model may contribute to the current understanding of cardiac arrhythmia. In addition, we aim to identify and further characterise the SHOX2-dependent signalling cascades by using cellular, molecular and biochemical approaches. Based on the high homology to SHOX, we are particularly interested in similarities, interactions and redundant functions of the two transcription factors as well as differences driven by highly specific factors and regulatory mechanisms during early development. Our work is funded by the Deutsche Forschungsgemeinschaft and the Eliteprogramm for Postdocs of the Landesstiftung BadenWürttemberg. Research Genetic Causes of Mental Retardation Project leader: Dr. V. Endris In the past few years research on genetic causes of mental retardation has made a lot of progress. Mental retardation is defined as retardation of the mental development that manifests itself in delayed cognitive, linguistic and social skills. About 3% of the population is affected by different degrees of severity of mental retardation, which can be measured by means of intelligence tests. It is our goal to determine and characterize genes with defects leading to mental retardation. Besides molecular genetic and neurobiological techniques, we have developed – in cooperation with the Mannheim ZI – an animal (mouse) model simulating a genetic mutation, which has originally been found in man. With the aid of this model, we intend to determine the exact mechanisms leading to mental retardation in patients suffering from this genetic defect. Our work is supported by “CellNetworks” and the SFB 488 (Special Research Unit) and – within the ‘Exzellenzcluster’ – funded by the DFG. Neurogastrointestinal and psychiatric disorders Head: PD Dr. B. Niesler Within the German Mental Retardation Networks (MRNET) – funded by the BMBF -, we are carrying out genome-wide SNP-chip analyses to determine DNA losses and gains in patients with mental retardation. One of these genes which – in a mutated form – leads to a defective connection of brain cells (neurons), is the “Mental disorder-associated GAP” protein, MEGAP Functional analyses have shown that MEGAP plays an important role in both formation and locomotion of neurons. The serotonin (5-Hydroxytryptamin, 5-HT) signalling system plays a key role in the modulation of bidirectional brain-gut interactions involved in cognition, emotions, emesis and digestive functions. Although alterations within the serotonergic system are assumed to contribute to conditions like irritable bowel syndrome (IBS) and eating disorders, its role in their pathomechanism still remains enigmatic. Patients often concomitantly suffer from anxiety and depression. 5-HT3 receptor antagonists are beneficial in the treatment of these conditions, but not all patients respond satisfyingly. We therefore hypothesized that 5HT3 receptor variants may influence 5-HT3 signalling in the brain-gut axis and thereby modify susceptibility to both, neurogastrointestinal and psychiatric disorders. Our main research focus in the past comprised the serotonin receptor system, in particular the serotonin type 3 receptor (5-HT3 R) diversity and its role in the aetiology of neuropsychiatric and neurogastrointestinal disorders. In our efforts to elucidate the heterogeneity of 5-HT3 receptors, we isolated and characterized three novel 5-HT3 (HTR3) genes. We have identified HTR3 variants involved in depression and anxiety as well as anorexia and IBS and in individual drug response (in particular, chemotherapy induced nausea and vomiting) which may serve as pharmacogenetic and biomarkers in the future. To gain further insight into the pathomechanism of disease and the role of 5-HT3 receptors, we established 5-HT3 antibodies and confirmed expression of all 5-HT3 receptor subunits in the human enteric nervous system, the little brain of the gut, and the gut mucosa. We have recently established the German IBSNet, in which five centers collect IBS samples to unravel genetic causes of IBS. We are currently characterising 5-HT3 receptor distribution and composition in the human gastrointestinal tract and the brain in order to identify tissue specific subtypes which we aim to target by microRNAs (transcript level) and specific drugs or antibodies (protein level) in order to establish novel treatment strategies for complex disorders such as neurogastrointestinal and psychiatric diseases. Our research is currently funded by Dr. Karl und Gerhard Schiller Foundation, the German Cancer Aid and the German Research Foundation. Research Department of Human Genetics Division Developmental Genetics Head: Prof. Dr. H. Steinbeisser Research in Human Genetics requires the establishment of model systems that allow experimental analyses of genes and gene products. The human system however, has only limited options for such functional and mechanistic analyses. The division Developmental Genetics uses amphibian embryos as experimental models to analyze the function of genes which not only control embryogenesis, but are also responsible for hereditary diseases of man. Our favored animal model is the clawed toad Xenopus laevis, whose embryos can be obtained in large numbers. Due to their large size they can easily be manipulated experimentally. Our project on the regulation of Wnt signaling is part of a research consortium called “Mechanisms, functions and evolution of Wntsignaling pathways” (FOR 1036) funded by the German Research Association (DFG). Research groups of the medical-and biological faculty of the universities Heidelberg and Karlsruhe are involved in this research network. Other important signaling molecules that we are working on are the Insulin-like growth factor binding proteins (IGFBPs), which not only modulate the IGF signaling pathway, but also interact with other regulatory modules within the cell. The interactions of the Wnt- and IGFsignaling pathways are analyzed in the context of embryogenesis and in the differentiation of pluripotent cells. This project is part of the DFG-funded Special Research Unit (SFB 873) “Maintenance and Differentiation of Stem Cells in Development and Disease”. Our research focuses on the analysis of signal transduction networks, which control cell differentiation and cell movements. Our goals are to describe new components of the signal cascades and to carry out functional analyses of mutated human proteins identified in patients. The Wnt-signaling pathways and their influence on cell adhesion and cell movement are at the center of our research. Wnt-mediated signals are necessary to establish the body axis of the embryo. Incorrect regulation of this signaling pathway can cause tumors, in particular in the intestinal tract. Molecular Genetics of Metabolism Head: Dr. H. Runz Elevated blood cholesterol levels are a major risk factor for atherosclerosis and premature death of coronary heart disease. Conversely, low levels of cholesterol in blood correlate with a reduced risk for these disorders, which constitute a leading cause of death in industrialized countries. Blood cholesterol levels are tightly regulated by cells, which take up cholesterol from the bloodstream. Our research aims to contribute to a better understanding of the molecular mechanisms how cells keep cholesterol levels balanced. In a long run, this may serve to develop new tools for diagnostics as well as therapy of cholesterol-related disorders. A main focus of our research is the identification and functional characterization of disease-relevant regulatory factors of cellular cholesterol homeostasis. For this, we apply (i) gene expression analyses in disease-relevant cell models, (ii) cell biological experiments that allow us to functionally allocate newly identified genes to the molecular network of known lipid regulatory mechanisms, and (iii) mutation analyses in patient samples. For the identification of novel candidate genes we follow a cell-based functional genome analysis strategy that involves automated microscopy and RNAinterference (RNAi) experiments. Within the framework of the Molecular Medicine Partnership Unit (MMPU), we use siRNA-microarrays that allow functional analyses of multiple genes at once and at a high throughput. Research Newly identified candidates are further characterized on a molecular level in order to understand how they contribute to cholesterolregulatory cellular processes or related medical conditions. A special interest of our group is the identification of disease modifying factors in NiemannPick Type C (NPC) disease. NPC disease is a rare autosomal-recessive lysosomal storage disease that is caused by mutations in NPC1 and NPC2 genes. Frequently, the disease presents in early childhood with visceral symptoms and fatal dysfunction of the central nervous system. Molecular Cytogenetics Group Identification of chromosomal instability in transgenic mice and embryonic stem cells of the mouse. Prof. Dr. A. Jauch The research of the molecular cytogenetic group focus on the application of molecularcytogenetic methods (fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and M-FISH for human and mouse) to identify chromosome aberrations which are involved in the developement and progression of tumour entities. Actual research topics: Identification of a new, in skin carcinogenesis relevant genetic aberration and its potential origin (in colaboration with Prof. Dr. P. Boukamp (DKFZ), funded by the Tumorzentrum Heidelberg/Mannheim 2008-2010) Tumour Genetics Prof. Dr. C.R. Bartram Relevance of chromosomal and centrosomal aberrations for the prognosis and pathogenesis in multiple myeloma (in cola- With our research we aim to understand which factors on a clinical, genetic and cellular level contribute to the highly variable course of NPC-disease. In cells, NPC disease is characterized by an accumulation of cholesterol in lysosomes. Using functional genomics, we analyze which genes are important for a cholesterol distribution that resembles, worsens or ameliorates this NPC cellular phenotype. boration with Prof. Dr. A. Krämer (DKFZ) and PD Dr. K. Neben (Innere Medizin V) funded by the Tumorzentrum Heidelberg/Mannheim 2008-2010) Characterization of chromosomal instability in malignant hematopoetic stem cells pathogenetic and prognostic relevance (in colaboration with Prof. Dr. A. Krämer (DKFZ) and Dr. H. Löffler (Innere Medizin V), funded by the Deutsche Krebshilfe 2008-2010). This working group is involved in various national and international joint collaborative projects and is currently focussing its research on two main areas: Genome-wide SNP Chip analyses (SNP= single nucleotide polymorphism) have enabled us to detect gains and losses of genetic material in malignant cells of patients suffering from acute lymphoblastic leukemia, helped us to identify genes that are causative in the development of leukemia, as well as proven successful when correlating genetic data with clinical diagnoses. Parallel to this, we use this high-throughput method in order to identify sequence variants or genes which may be indicative of a higher personal predisposition to leukemia. Secondly, our group makes use of a similar range of techniques in order to isolate genes or DNA markers playing an important role in the hereditary disposition for breast cancer. Apart from the well-known genes BRCA 1 and BRCA 2, which have a decisive influence on tumour development in about 30 % of the families with a genetic predisposition for cancer, we identify those genes which- taken on their ownonly have a minor influence on the disposition for cancer, however, which can provide invaluable insights into tumour development as well as its clinical relevance. Research Clinical Genetics 65, BC Research projects and studies PD Dr. Dr. U. Moog Research activities within Clinical Genetics serve as a link between patient care and basic molecular research. They focus on identifying the genetic background of various diseases and on their functional characterization. A general prerequisite is the availability of clinically well characterized patient cohorts established by standardized examinations with concerted clinical criteria, often comprising dysmorphic signs, and the systematic registration of clinical data. Care is taken to assure that patients are in consent and properly informed. Identification of autosomal genes for psychomotor retardation within MRNET (German Mental Retardation Network) Study of the prevalence of inborn errors of metabolism as a cause of mental retardation Genotype-phenotype correlation in mucopolysaccharidosis IIIB Pathogenesis of rare neurocutaneous disorders (Encephalocraniocutaneous Lipomatosis, Oculocerebrocutaneous Syndrome) Genetic Epidemiology Amongst the clinical genetic research activities, diseases of particular interest are those that cause psychomotor retardation in children. This includes a group of inborn errors of metabolism and of rare syndromes. Dr. C. Fischer Genetic Epidemiology employs statistical methods in order to systematically investigate the role and interaction of genetic and environmental risk factors as regards the development and progression of diseases. Our studies are either based on families with a hereditary disposition for a specific disease, or we obtain random samples from not related patients with healthy controls. The objective of our working group is the statistical maintenance of linkage analyses and association studies. This ranges from the initial sample size calculations to the evaluation of the data and interpretation of the results. 55, BC 52, BC 53, BC 43, BC ? Another focus of our work is to assess and calculate the risk of individual families to develop certain diseases. Families consulting our Genetic Councelling often wish to obtain information as regards the probablility to develop specific diseases, e.g. breast cancer, later in life. Say, if the genes BRCA1 and BRCA2 show no evidence of molecular mutations, it is possible to give an estimation of the probability to develop the disease. These calculations are based on information about the age of both ill and healthy family members, previous diseases or cancer as well as other environmental risk factors. A biological-statistical modelling plays an important part in this. The result of the calculations directly influences the respective medical treatment of advice seeking individuals. The probability to develop a disease can define high-risk groups, which clearly benefit from a more frequent screening programme or other prophylactic treatments such as surgeries. Teaching The Institute of Human Genetics is extensively involved in the teaching of students of medicine and biology in Heidelberg, as well as in the specialist training in human genetics and genetic epidemiology and in promoting the junior staff in special programmes. In addition to the extensive range of teaching for medical students courses in the field of human genetics and human molecular genetics are also offered at the Faculty of Biosciences, where Profs. Bartram, Buselmaier and Steinbeisser are co-opted members. Courses of study at the Faculty of Biosciences: Within the framework bridging the Life Sciences and the Humanities, interdisciplinary doctoral theses are supervised via the "Marsilius Kolleg" or the "Interdisciplinary Forum for Bioscience and Cultural Studies". I Teaching for Medical Students Teaching for Biology Students Within the realm of medicine, human genetics has a double bridging-function. On the one hand, it is linked with the basic subjects of the Life Sciences and on the other, to the clinical disciplines. In this respect, human genetics is one of the few subjects to be found in the preclinical as well as the HeiCuMed clinical curriculum. Traditionally, the Institute of Human Genetics always had a good relationship with the Faculty of Biosciences. Currently there are 16 (science) students from the Faculty of Biosciences who are working on their doctoral thesis in the Institute of Human Genetics. Together with the Department of Cell Biology, the Institute of Human Genetics organises a teaching unit which was formerly known as “Biology for Physicans”. This consists of a series of lectures on “The Basics of Human Genetics” plus a practical course. The students are divided into small groups and each student spends 3 full days with this group performing various experiments. Explicit reference is made to clinically relevant aspects. The vast majority of the students pass the Human Genetics part of the integrated (written) examination in their first attempt and later, when it comes to the preliminary medical examination the Heidelberg students have for many years consistently lead national rankings in this field. In the final academic year, Human Genetics appears again as a compulsory subject and is graded in the final state examination. Here the questions are centered on genetic counselling as well as molecular genetic and cytogenetic diagnostics. In additon, there are extensive discussions on ethical aspects of, for example, prenatal diagnostics and the clarification of disposition for disease among individuals who are (still) healthy (predictive diagnositcs). The presentation of patients is an important part of the “Clinical Genetics” lectures and this serves to illustrate that medicine has to do with sick people and not diseases (L. Krehl). A substantial part of the course content receives extensive coverage in the module Human Genetics where students work in small groups over a two-week period. The various working groups in the institute participate in the curricula for the Bachelor, Master and Diploma degree courses in the form of seminars, lectures and practical courses. The spectrum of offerings ranges from courses (seminars and lectures) dealing with current topics in the fields of human genetics, molecular genetics and developmental genetics to a three week practical course for biology students with intensive supervision by several working groups of the institute eagerly imparting theoretical and practical knowledge. Within the framework of the International “Hoffmann-Berling Graduate Schule” the Institute of Human Genetics offers a structured training programme for doctoral students. © Photos Media Center University Hospital Heidelberg Last update: January 2011