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Research objectives

Genome Biology
Understanding effects of genotypic variation on phenotypic diversity

The research in the Cuppen group focuses on functional and personal genomics. To this end, experimental and bioinformatic approaches are used in model organisms as well as patient material. The general aim is to understand the function of genomic elements and the effects of genetic variation on phenotypic diversity.

DNA sequencing:
The Cuppen group has a long track record in high-throughput DNA sequencing and was the first in Europe to implement AB’s next-generation sequencing technology SOLiD (fig. 1). This platform is now used for (whole) genome resequencing and mutation detection/discovery, but also for small RNA sequencing, ChIP-Seq, and structural variation detection.
New applications and improvements to existing protocols are continuously being developed in close collaboration with several companies. Furthermore, the group is working on a variety of bioinformatic tools for the analysis, interpretation and integration of next-generation sequencing and other types of genomics data.
Next-generation sequencing techniques are used to systematically collect genetic and epi-genetic information in genetic model systems (fig. 2).

Genetic model systems:

We are using two types of genetic models. A) ENU-induced mutants and B) the rat recombinant inbred panel HXB/BXH.
A) We are using a universal approach, target-selected mutagenesis, to inactivate genes in model organisms, including C.elegans, zebrafish and the rat. Random DNA mutations are introduced in the germ line of an organism using chemical (usually ethyl-N-nitrosourea, ENU) mutagenesis. These animals are used to generate a large F1 population that is screened for induced mutations in genes of interest. Currently, we use high-throughput dideoxy sequencing for the discovery of mutations, but we are also exploring next-generation sequencing technology to improve on the efficiency of the procedure.
B) The rat recombinant inbred (RI) panel (fig. 3)is used as a simplified genetic system with a limited amount of genetic variation. The panel consist of 30 inbred lines that are derived from a cross of two inbred rat strains (SHR and BN-Lx). F2 progeny from this cross, which are mosaics of the genetic backgrounds of the parental lines, were incrossed for over 80 generations (M. Pravenec, Prague), resulting in inbred lines that reflect a small outbred population and form a renewable source of genetically identical animals. This panel is now systematically characterized for genome-wide genetic and epi-genetic parameters (using next-generation sequencing technology) to understand the effects of genetic variation (SNPs, structural variation) on phenotypic diversity (e.g.quantitative and qualitative gene expression patterns in various tissues).

Student projects:

Please contact Edwin Cuppen when you are interested in doing a rotation project in any of the above mentioned research areas (either wet-lab or bioinformatic).

About the group leader
Publication list

 
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Figure 1: raw results from SOLiD sequencing. A total of more than 300 million beads can be sequenced in a single run, resulting in more than 10 billion base pairs per experiment

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Figure 2: microRNA expression in various rat tissues and strains as determined by digital gene expression profiling using next-generation sequencing

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Figure 3: schematic overview of the generation of the rat recombinant (RI) panel HXB/BXH