Meet some of our invited speakers

A professor Molecular Cytogenetics at the University of Leuven and also faculty member of the European Genetics foundation heading the Constitutional Cytogenetics unit of the Center of Human Genetics, Leuven, Belgium and coordinating the genomic core at the University Hospital. Dr. Joris R. Vermeesch graduated at the University of Nebraska, Lincoln, USA for his studies on telomere biochemistry. Subsequently Dr. Joris R. Vermeesch joined the Center of Human Genetics in Leuven, Belgium during which period he was mainly interested in the structure and evolution of telomeres and centromeres and the development of a human artificial chromosome. Before taking up his current position, Dr. Joris R. Vermeesch was head of the genomics unit in the basic research division of Aventis CropScience and responsible for large scale genome analyses in several crops. Dr. Joris R. Vermeesch is currently president-elect of the Belgium Society of Human Genetics.

Research interests
The laboratory has three focus areas. First, the laboratory is at the forefront of genomic technology development and implementation. During the last five years, the laboratory focused on implementing array CGH in molecular diagnostics and on novel applications of array CGH. A major area of attention is the detection of genome wide CNV and SNP detection in single cells. Currently, the laboratory is developing methods massive parallel sequencing applications in preimplantation, prenatal and postnatal diagnosis. Second, in collaboration with clinical geneticists, the laboratory actively seeks to define the molecular causes of developmental, mental and behavioural disturbances. The group is partner of the SymbioSys, the systems biology center of excellence in computational biology to mine high throughput data analysis tools and to identify novel gene functions through data fusion methods. Third, based on the large cytogenetic screens, the laboratory is interested in understanding the mechanisms underlying chromosomal instability.

Research interests of Dr. Joris R. Vermeesch are: The constitutional cytogenetics laboratory, embedded within the clinical genetics unit of the university hospital, is responsible for the chromosome analysis for preimplantation, prenatal and postnatal diagnosis. Aberrant chromosome number and/or morphology are associated with miscarriages, congenital malformations, developmental disorders, mental retardation, behavioural problems and infertility. The identification of such chromosomal aberrations helps the diagnosis, determines the molecular cause of many disorders and helps family planning in affected families. Besides it’s routine diagnostic activities the laboratory is actively involved in research. The research activities focus on two areas. On the one hand, the laboratory is involved with the development of novel technologies in the area of chromosome analysis and genomics. On the other hand, in collaboration with the clinical geneticists, the laboratory actively seeks to define the molecular causes of developmental, mental and behavioural disturbances. To this end the laboratory takes advantage of the many chromosomal aberrations that are identified in patients and the advent of the human genome project. The international collaborative human genome project has provided us with the sequence of the human genome, the identification of the putative genes within our genome and with the tools to analyse this genome. Using these tools, we can readily analyse chromosomal aberrations at the molecular level and identify the genes causing the observed phenotypic aberrations.

Anna is head of Bioinformatics at the Medical Genetics Centre Munich and a research coordinator for the German Human Genome Archive (GHGA) at the Helmholtz Munich. Since 2019 she is also a scientific collaborator at UCSC Genome Browser.

She has a PhD in human genetics and is a specialist in the field of genome sequencing and data analysis with a strong background in the clinical genetics of Rare Diseases. She has many years of experience in interdisciplinary management of laboratory technology, bioinformatics, and scientific development in academic, clinical and private practice environments.

Anna is an advocate for the use of best practices in FAIR data management and sharing strategies to maximize the use of OMICS data and improve the diagnosis of genetic disorders. She has contributed to publications on guidelines for utilization of next-generation sequencing approaches in clinical genetics testing and she is assessor of the External Quality Assessment scheme for Charcot-Marie-Tooth disease within the European Genetics Quality Network (EMQN) framework. She strongly believes in the power of education and is therefore an active member of the HUGO Education Committee and an instructor at the Variant Effect Prediction Training Course (VEPTC).

Professor Christian Gilissen's group develops and applies bioinformatics methods to gain insight into the causes and mechanisms of genetic disorders such as intellectual disability.

1. The development and application of bioinformatics methods and new technologies to better identify genetic variation

Next-generation sequencing techniques such as exome or whole genome sequencing have become the standard techniques for  genetic testing and research. In addition, new technologies that allows us to better identify variation in the human genome are steadily developed. Our department is at the forefront of testing and implementing these technologies. With all of these technologies, new bioinformatics methods are required and we have done performed various studies showing the clinical utility of novel techniques, or developing novel methods that improve on variant identification of existing technologies:

Accurate detection of clinically relevant uniparental disomy from exome sequencing data. Yauy K, de Leeuw N, Yntema, HG, Pfundt R#, Gilissen C#. Genet Med. 2019 Nov 26. PMID:31767986.

Comparison of Exome and Genome Sequencing Technologies for the Complete Capture of Protein Coding Regions.Lelieveld SH, Spielmann M, Mundlos S, Veltman JA, Gilissen C. Hum Mutat. 2015 May 14. PMID: 25973577.

Genome sequencing identifies major causes of severe intellectual disability.Gilissen C*, Hehir-Kwa JY*, … Brunner HG#, Vissers LELM#, Veltman JA#. Nature. 2014 Jul 17;511(7509):344-7. PMID: 24896178.

A Post-Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases. Neveling K*, Feenstra I*, Gilissen C*, … Scheffer H, Nelen MR. Hum Mutat. 2013 Dec;34(12):1721-6. PMID: 24123792.

In ongoing studies we’re investigating the potential of long-read sequencing technologies for medical genetics, and the recycling of exome sequencing data for identifying novel types of genetic variation.

2. The development and application of bioinformatics data-integration methods to understand the effect of genetic variation in the context of human disease, in order to identify the genetic cause of disease

With the availability of large datasets of genetics information, we can try and understand more about the biology of disease by performing large scale data-integration, either integrating different large genetic datasets, or by combining genetics with other types of biological data. We have worked on using statistical approaches to identify candidate genes in which mutations give rise to neurodevelopmental disorders:

Integrating healthcare and research genetic data empowers the discovery of 49 novel developmental disorders.Joanna Kaplanis*, Kaitlin E. Samocha*, Laurens Wiel*, Zhancheng Zhang*,  … Matthew E. Hurles#, Christian Gilissen#, Kyle Retterer#. bioRxiv 797787; doi: https://doi.org/10.1101/797787

Spatial Clustering of de Novo Missense Mutations Identifies Candidate Neurodevelopmental Disorder-Associated Genes. Lelieveld SH*, Wiel L*, … Vissers LELM#, Gilissen C#. Am J Hum Genet. 2017 Aug 30. PMID: 28867141.

Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH*, Reijnders MRF*, … , Vissers LELM#, Brunner HG#, Gilissen C#. Nat Neurosci. 2016 Aug 1. PMID: 27479843.

3. Bioinformatic investigations into the biological mechanisms that underlie new mutations in humans

De novo mutations are a frequent cause of human disease, such as neurodevelopmental disorders but are also the drivers of human evolution. However, we still know very little about why and how exactly these types of mutations arise. Through bioinformatics analysis of large whole genome sequencing datasets we try to identify patterns of these de novo mutations that give us insight into the likely underlying mechanisms that cause these mutations to occur:

De Novo Mutations Reflect Development and Aging of the Human Germline.Goldmann JM, Veltman JA, Gilissen C. Trends Genet. 2019 Oct 11. PMID: 31610893.

Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double strand-break incidence.Goldmann JM*, Seplyarskiy VB*, Wong WSW*, Vilboux T, Neerincx PB, Bodian DL, Solomon BD, Veltman JA, Deeken JF, Gilissen C#, Niederhuber JE#. Nat Genet. 2018 Mar 5. PMID: 29507425.

Parent-of-origin specific signatures of de novo mutations. Goldmann JM*, Wong WSW*, Pinelli M, Farrah T, Bodian D, Stittrich AB, Glusman G, Vissers LELM, Hoischen A, Roach JC, Vockley JG, Veltman JA, Solomon BD, Gilissen C#, Niederhuber JE#. Nat Genet. 2016 Jul 20. PMID: 27322544. 

Patient care

This research group is strongly connected to the division of Genome Diagnostics that offers state-of-the-art genetic testing for patients with genetic disorders. This allows us to test and validate new bioinformatic methods on large cohorts of patient data, but also facilitates the quick adoption of new techniques into patient care.
 

Johan den Dunnen studied biology at the Catholic University Nijmegen (Nederland). In the same university he received his PhD in Molecular Biology for his work on the "Evolution of eye-lens crystallin genes". After his PhD he moved to the department of Human Genetics (Leiden University) and became involved in the search for the gene causing Duchenne/Becker muscular dystrophy. He is currently employed at the Center for Human and Clinical Genetics (Leiden University Medical Center, Leiden, Nederland), studying genetic disease in general and neuromuscular disorders (DMD/BMD, LGMD) in particular. As professor in "Medical Genomics" he focuses on the use of new high-throughput technology in research and diagnosis of genetic disease, in particular the development of methods to detect DNA variants and the application of next generation sequencing. To spread the laboratories knowledge on hereditary muscle disease he initiated the "Leiden Muscular Dystrophy pages" (http://www.DMD.nl). As part of these efforts he currently curates over 50 gene sequence variant databases. His group developed the freely available LSDB-in-a-Box software package LOVD, the Mutalyzer tool (HGVS sequence variant description) and he participates in the EU FP7 Gen2Phen project (WP leader for gene variant databases [LSDBs]). 

Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven Belgium

Thierry Voet graduated with a Master in Bioscience Engineering: Cell and Gene Biotechnology from the University of Leuven (KU Leuven, Belgium), and holds an inter-university post-graduate in Human Genetics. Following his PhD in the Human Genome Laboratory at KU Leuven, he pioneered single-cell microarray analyses, and in 2010, he joined in the Cancer Genome Project at the Wellcome Sanger Institute (Cambridge, UK) to explore next-generation sequencing technologies for single-cell genomics, which led to an Associate Faculty membership. In 2014, he became Associate Professor at KU Leuven following a tenure track, and was appointed Professor in 2017 and Full Professor in 2022. Recently, he founded the interdisciplinary KU Leuven Institute for Single Cell Omics (LISCO) together with 33 colleagues, of which he is also director. His research focuses on (1) the development of methods for single-cell and spatial multi-omics, and (2) their application to study the biology of cellular heterogeneity in human development, aging and disease.

Andreas Laner, PhD

Head of Genomics Program

Areas of Specialization

• Genetics of hereditary cancer syndromes
• Next-generation sequencing applications
• Interpretation and classification of sequence variants

Education & Experience

• Diploma in Biology, Ludwig Maximilian University, Munich
• PhD, Ludwig Maximilian University, Munich

Professional affiliations

• MGZ Munich, Head of Genomics Applications
• Member, European Society of Human Genetics
• Curator, Leiden Open Variation Database
• Organizational Committee, Variant Effect Prediction Training Course, Crete 2016
• Scientific Program Committee, 14th International Symposium on Variants in the Genome, Santiago de Compostela 2017