Medical Genetics

Completion of the human genome project and the massive technical advances in recent years have had a major impact on clarifying genetic causes of a vast number of complex and monogenic diseases.

Our high-profile research facet of medical genetics has made great strides through genetic analysis of CVD and cardiac infarctions, Parkinson’s disease, diverse kinds of dystonia, and the Cornelia de Lange syndrome. Despite such success that came from genome-wide associative and coupling studies, the variants discovered so far could explain only a small fraction of the heritability of most diseases. Hence, this phenomenon of “missing heritability” still needs to be clarified.

Next generation sequencing (NGS) is a highly promising approach to fill this apparent gap. With this new molecular biology technology, it is now possible for a reasonable number of persons to sequence the human genome at a reasonable cost. At our Universität zu Lübeck, we established a
pipeline
in the past few years to evaluate these highly complex data sets.

The functional characterisation
in vitro
and
in vivo
is relevant for identifying genetic variants.
A key technology of relevance is the generation of induced pluripotent stem cells (iPS) and their associated transdifferentiation in the target tissue, such as neurons – a Nobel Prize was awarded in 2012 for this discovery.
The tissues, which have endogenic mutations and are, otherwise, either not accessible or very hard to access can now be accessed for investigating and validating genetic outcomes in human cell models. Over the past few years, the staff at the
Institute for Neurogenetics
has quite successfully set up such a platform to produce and test iPS cells.

In addition to the NGS and iPS platform, we were able to set up another platform for systematic phenotyping of cardiovascular and dermatological knock-out mouse models. Plans over the coming years are to expand the portfolio of functional genomics in Lübeck, by using the zebra fish as another model to research arteriosclerosis and drosophila as models of Parkinson’s disease.