By the year 2020, whole-genome sequencing will be a standard tool in medical research. Many patients being referred to a physician for a diagnosis have their genome sequenced as a first tier diagnostic test, and in addition a growing group of people will have their genome sequenced as part of a personalized disease prevention strategy. The focus of medical genetic research will be on clinical interpretation of sequence data, integration with functional studies, and translation into clinical applications.
The Genomics Disorders Group is part of the Department of Human Genetics of the Radboudumc, one of the largest departments of human genetics in Europe. Our group has a long standing interest in using state-of-the-art genomics technologies and bioinformatics approaches to detect and interpret rare genomic variation in disease, with a particular focus on de novo mutations and structural genomic variation. We use both common and rare forms of intellectual disability as model disorders in our research. In collaboration, we expand this to other disorders such as chronic immune disorders and male infertility. Our ambition is to play a significant role in genomic medicine. We aim to achieve this by improving our understanding of the causes underlying genomic disorders and by translating our technological, biological and bioinformatic expertise into routine clinical applications. We are strongly embedded in both the research and diagnostic divisions of our department, allowing both a rapid and a reliable implementation of novel genomics approaches in clinical care.
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 two areas in human genetics in which our Genomic Disorders group is involved:
Understanding the genetic causes of severe early-onset disorders such as intellectual disability
For a long time it was unclear why these diseases associated with reduced fitness remain so frequent in our population. Our group recently showed that rare de novo mutations may play a pivotal role in severe intellectual disability. 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. We will continue to study the role of de novo mutations in intellectual disability, but will also expand this to male infertility and other disorders with an impact on fitness. In addition, we will expand our research to study more complex forms of inheritance.
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. 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.