University Medical Center Groningen: Department of Genetics

Our Department of Genetics
was founded 65 years ago, in 1951. We have about 250 people
working here. The main emphasis is
on complex genetic diseases: How genetic variation translates
into phenotypic variation. We use patient materials
and a big population biobank… …of 167,000 people at the moment. Which we leverage with a lot of
‘omics’ data. We cover the full path from gene dis-
covery to implementation in the clinic. A nice example is preconception testing. We’re developing a test so couples
can test, before they start a family… …whether they both carry
a severe mutation… …and have a high chance of having
a child with a severe disease. This is currently being implemented
in the clinic, with the help of GPs. I work on a project for determining
the diagnosis in critically ill new-borns… …in the neonatal ICUs.
We sequence their whole genome… …and we focus on older genes
involved in Mendelian diseases. Intensive treatment has a very high
impact on parents and children. Especially critically ill, young children. If you can use rapid whole
genome sequencing… …you shorten the period of uncertainty
for parents… …but also for the medical staff. This period for rapid whole genome
sequencing is now about two weeks. We aim to reduce that
to only a few days. When we have a diagnosis,
medical decisions can be made. Like stopping treatment
or even intensifying treatment… …when you know the prognosis is good. We’re getting out of the comfort zone
of standard clinical genetics. We have to work on the practicalities… …but also on the ethical and legal
aspects associated with this. It’s important to realise that genetics
will be increasingly important… …for many medical disciplines. It will
also become much more complex. There are so many genetic risk factors
to take into consideration… …and also the interaction with
all sorts of environmental risk factors. It will be difficult to weigh all these
things and make clinical decisions. We’re developing several things
to support that. We’re building a virtual clinic
for genomic medicine… …so students can more easily study
these complex things. We’re also developing
decision-support systems. First within our pharmaco-genetics
programme. It’s important to help the clinicians
decide, in real time, in their offices… …what the best course of action is. Epidermolysis Bullosa
is a devastating skin disorder. Patients get blisters from birth, all over
the body, accompanied by scarring. There are many different forms
of Epidermolysis Bullosa. The most severe forms are fatal
within one or two years. There is currently no cure for EB.
The treatment is mainly symptomatic. We’re trying to remove part of the gene
by using specific RNA molecules. So we try to remove the part
where the mutation is located… …and restore the expression of the
protein that is absent in the patient. We’ve done successful experiments
in cells and in mice. They showed very promising results. So I’m hopeful that we can bring
this approach, exon skipping… …to the clinic in a couple of years. The main focus of my research
in clinical dysmorphology… …is children with rare chromosome
disorders and Charge syndrome. I also study the implementation of new
genetic techniques in diagnostics… …of children with developmental delay
and congenital abnormalities. We need to compare all these different
chromosome abnormalities… …and the clinical outcome, to predict
what can be expected in a specific child. This piece of art was made by a child
with a chromosome 6 disorder. Our social media project started with
a chromosome 6 Facebook group… …of parents who met via the Internet. With this Facebook group we
successfully collected information… …of children with chromosome 6
abnormalities worldwide. Within months we had more informa-
tion than was available in the literature. In the last few years, thousands of
genetic risk factors have been found… …that cause disease, but for many
it’s still unclear how they cause it. We currently don’t know
what kind of cell types are affected… …or what kind of pathways
are disrupted. My group aims to take
a systems genetics approach… …that uses a lot of public data. We also rely on Lifelines-Deep,
a cohort of 1,500 individuals… …from whom we have collected a lot of
different molecular information… …including gene expression, methyl-
ation, microbiome, metabolite data. Right now there’s a real explosion
of very interesting big data. It’s this unique combination
of data generation, and also… …the development of novel tools and
methods to analyse these data… …that permits us to answer
very interesting medical questions. Our department has a lot of people
of many nationalities and disciplines. That helps to think about problems
in a different way. We don’t have any offices.
Everybody has a flexible working place. You could be next to somebody working
on something completely different. And the following day
it’s another person again. That really helps to think
about problems in different ways. The future of our department is
really to move into precision medicine. It no longer matters whether we’re
dealing with families or single patients. Whether it’s a complex genetic disease
or a more Mendelian disease. We really want to use genome
sequence data to help people… …in either their treatment
or the diagnosis of their disease.

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