Translational Genomics

Translational Genomics

The Translational Genomics team focuses on the evaluation and optimization of novel genomic technologies for diagnostic implementation for the study of human genetic disease. Research has led to improved patient care by the implementation of array CGH for patients with intellectual disability (ID) into routine diagnostics as well as by the identification of novel syndromes and disease-causing genes.

In 2008, an obtained VENI grant was used to apply next generation sequencing to identify novel disease genes. The team was the first to use family-based whole exome sequencing for the identification of de novo mutations creating a paradigm shift in the field of medical genetics. Also, the achieved results provided a founding base to assess the diagnostic yield of exome sequencing in a routine diagnostic setting. The next frontiers in routine clinical diagnosis will, amongst others, include the implementation of whole genome sequencing as well as improving the clinical interpretation of (non-coding) genetic variation.

Projects:

1. NWO VENI This research project focuses on how the combinations of genetic mutations can result in intellectual disability.

2. ZONMW TOP aims to extend a database with 10,000 clinically well characterized ID patients, to develop a universally applicable method that judges the likelihood of any conserved candidate gene to be an ID gene, generate disease-relevant functional data on at least a 100 candidate genes and validate 30-40 novel ID genes with specific ID phenotypes.

Key publications:

Understanding the Psychosocial Effects of WES Test Results on Parents of Children with Rare Diseases. Krabbenborg L, Vissers LE, Schieving J, Kleefstra T, Kamsteeg EJ, Veltman JA, Willemsen MA, Van der Burg S.
J Genet Couns. 2016 Apr 20. [Epub ahead of print]

Standardized phenotyping enhances Mendelian disease gene identification. Vissers LE, Veltman JA.
Nat Genet. 2015 Oct 28;47(11):1222-4. doi: 10.1038/ng.3425.

Genetic studies in intellectual disability and related disorders. Vissers LE, Gilissen C, Veltman JA.
Nat Rev Genet. 2016 Jan;17(1):9-18. doi: 10.1038/nrg3999. Epub 2015 Oct 27.

Whole-genome sequence variation, population structure and demographic history of the Dutch population Genome of the Netherlands Consortium.
Nat Genet. 2014 Aug;46(8):818-25. doi: 10.1038/ng.3021. Epub 2014 Jun 29.

Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome Vissers LE1, Bonetti M2, Paardekooper Overman J2, Nillesen WM3, Frints SG4, de Ligt J1, Zampino G5, Justino A6, Machado JC6, Schepens M3, Brunner HG1, Veltman JA1, Scheffer H3, Gros P7, Costa JL6, Tartaglia M8, van der Burgt I3, Yntema HG9, den Hertog J10.
Eur J Hum Genet. 2014 Jun 18. doi: 10.1038/ejhg.2014.115. [Epub ahead of print]