The LUMC group has extensive experience in RNA-based gene expression profiling (incl. whole genome exon and tiling arrays), Chromatine Immuno-Precipitation, re-sequencing, SNP-typing and the detection of Copy Number Variation (deletions and duplications), using both arrays and massive parallel sequencing technologies as well as with the associated data analysis (bioinformatics).
LUMC participates in several activities in the project, performing such research as the detection of quantitative changes in the genome (Copy Number Variation). Many techniques were developed to identify these changes, incl. Pulsed-Filed Gel-Electrophoresis, multiplex amplifiable probe hybridization (MAPH), multiplex ligation-dependent probe amplification (MLPA), micro-arrays (incl. flow-through) and beads. The group has a patent on Array-on-Demand (AoD), currently developed in collaboration with FlexGen (Leiden, NL). This technology facilitates the free design and production of arrays with the simple input of oligonucleotide sequences (up to > 60 nucleotides and of different length when desired). This technology is ideal when designing first arrays (both for CNV detection and re-sequencing), giving the possibility to quickly, in-house and economically test several design formats, before a more definitive array is produced in larger quantities. Recent results, based on mtDNA re-sequencing using FlexGen arrays, indicate that data quality is at least similar to that of other array formats.
Johan Den Dunnen
Johan den Dunnen (PhD) is professor in Medical Genomics and a staff member at the departments of Human and Clinical Genetics. He has a long-standing interest in research and diagnosis of DMD and introduced several diagnostic techniques, incl. pulsed-field gel-electrophoresis and the Protein Truncation Test. He initiated the Leiden Muscular Dystrophy pages www.DMD.nl, curates the DMD mutation database (storing all DMD mutations published and submitted worldwide) and he established the LOVD system to collect and display gene variants, which will be employed to set up the Dutch DMD patient registry. Finally, he is the original autor intellectualis of the exon skipping approach and has supervised the generation of the hDMD mouse model, containing a full copy of the human DMD gene in the mouse genome. The human gene functionally compensates the lack of mouse dystrophin in the mdx mouse, so hDMD/mdx mice are healthy. This mouse models allows testing human specific AONs in vivo.