Mission and vision

By the year 2020, whole-genome sequencing will be a standard tool in medical research. Any patient being referred to a physician for diagnosis has their entire genome sequenced prior to any other diagnostic procedure. The focus of medical genetic research will therefore be on clinical interpretation of sequence data, integration with functional studies, and translation into clinical applications. The complexity of disease etiology makes large-scale integrated approaches essential, yet it requires medical research to be done on a much larger scale.

In the coming years consortia of collaborative public and private parties will be initiated to tackle specific medical challenges. It is the mission of the Genomic Disorders Group to play a leading role within these large consortia, specifically for the detection and interpretation of rare genetic variation underlying disease, as well as for translation into clinical applications. The primary focus of the Genomic Disorders Group is on mental disorders with rare monogenetic inheritance, with possible extension to other (more complex) disorders. The Genomic Disorders Group will take a leading role in national and European medical sequence consortia and will be the driving force for a virtual centre of expertise on medical genome sequencing.

Main research themes:

The identification of the genetic cause of a disease enables molecular diagnosis and carrier testing in the patient and his or her family. This is of great importance for patient management and family counseling, and serves as a starting point for therapeutic interventions. Novel sequencing technologies in combination with novel bioinformatic approaches now for the first time allow us to rapidly and affordably study the entire genome of a patient and look for pathogenic variation. Approaches such as whole genome and whole exome sequencing are changing at least three areas in human genetics in which our Genomic Disorders group is involved:

Speeding up Mendelian disease gene identification

There are thousands of clinically well-defined syndromes for which the genetic cause is not yet known. The majority of disease genes causing these syndromes will be identified by these unbiased genome sequencing approaches in the coming 3 years and it is our group's ambition to contribute significantly to this disease gene identification process.

Understanding the genetic causes of common neurodevelopmental disorders such as intellectual disability, autism and schizophrenia

For a long time it was unclear why these diseases associated with reduced fitness remain so frequent in our population. Our group recently showed by using a family-based exome sequencing approach that rare de novo mutations may play a pivotal role in these diseases. In the coming years we aim to provide critical knowledge on the frequency, location, risk factors and consequences of de novo mutations in health and disease.

Improving genome diagnosis

Whole genome sequencing can be performed as a high throughput test for all genetic diseases. This significantly reduces the complexity of the genetic diagnostic setting in which each disease gene requires a different test and different forms of genomic variation require different assays (i.e. Sanger sequencing for point mutations, genomic microarrays for genomic copy number variation). This will significantly improve the diagnostic yield both in rare genetic disorders for which disease genes were unknown and/or genetic testing was not offered, as well as in genetically heterogeneous diseases for which this is the only comprehensive assay. Together with our colleagues from genome diagnostics we want to be frontrunners in the diagnostic implementation of novel genomics technologies such as whole exome and whole genome sequencing.

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