Download Institute of Human Genetics - UniversitätsKlinikum Heidelberg

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
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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.
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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