Human and Clinical Genetics, Leiden University Medical Center

Genome Technology & Genetic Disease

(modified last September, 2008)

We always welcome the help of students and stagiaires. For detailed information on the current possibilities please contact us.

Current research subjects

• Genome Technology
• BioInformatics  -  see Bioinformatics tools and support
• Microarray Analysis Group  (Judith Boer)
  • analysis of microarray data for gene expression, methylation, and DNA copy number
    • yearly course: "Analysis of microarray gene expression data"
  • integration of multiple sources of high-throughput omics data
• Bioinformatics Support Group  (Peter Taschner)
  • computer analysis of sequenced DNA, data mining, database searches (molecular biology, molecular genetics and molecular medicine)
  • Mutalyzer (MUTAtion anaLYZER) - determine the effect of sequence variations in disease genes (pathogenic or not) 
• Leiden Muscular Dystrophy pages  (Johan den Dunnen)
  • Locus-Specific gene variation DataBases (LSDBs)
    • LOVD (Leiden Open source DNA Variation Database)
  • from genotype to phenotype
    • EU 7^th framework Gen2Phen project
• Biosemantics  (Barend Mons)  -  see http://www.biosemantics.org
• develop and validate advanced techniques for the processing and analysis of large, complex, and heterogeneous medical and biological data sets  -  in collaboration with Medical Informatics, ErasmusMC, ROTTERDAM, Nederland)
• New technologies  (Johan den Dunnen)
• improvement of mutation-directed DNA-diagnosis to facilitate counseling and prevention of genetic diseases
  • point mutation scanning  -  MCA  (high-resolution Melting Curve Analysis)
  • detecting one in a million  -  PAP  (pyrophosphorolysis-activated polymerization)
  • deletion/duplication detection  -  array, MLPA
  • SNP-typing
• next-generations sequencing
  towards sequencing complete human genomes (see first female DNA sequence)
  • current applications; gene expression profiling (SAGE-like signature sequencing, CAGE sequencing [5', 3' RNA ends], whole transcript, micro-RNA profiling), captured sequences (ChIP sequencing, methylation sequencing, nucleosomal DNA, RNA-IP, viral integration), SNP discovery, re-sequencing (mtDNA, candidate disease gene/region [long-range PCR, array-hyb capture, pooled sample pooling], microbial genomes, human genome), deep-sequencing (viral mutation load, viral evolution, metagenomics (archeological samples, gut flora, species diversity), de novo sequencing (bacteria, simple eukaryotes (moulds)
    all these applications include development of bioinformatic analysis (analysis pipe line construction)
• copy number variation in the human genome (arrayCGH / MLPA):
• genomics / transcriptomics facility (Leiden Genome Technology Center)
• DNA-sequencing
  • next-generation sequencing (Illumina/Solex technology)
• clone distribution / screening of DNA-clone libraries (YAC, PAC, cosmid, cDNA)
• array technology (DNA and protein)
  • Array-on-Demand Technology in collaboration with FlexGen (LEIDEN, Nederland)
  • Flow-Through Micro-arrays in collaboration with PamGene. (DEN BOSCH, Nederland)
• SNP-typing & discovery
• real-time PCR
  • Biomark (Fluidigm); 96 x 96 qPCR, digital PCR, MCA
• high resolution Melting Curve Analysis

• Genetic disease
  apply new technology to unravel the cause of genetic disease and to improve mutation-directed DNA-diagnosis to facilitate their counseling and prevention
• Neurodegenerative disorders  (Willeke van Roon)
  • Huntington's disease (HD)
• Neuromuscular disorders    (Peter-Bram 't Hoen)
  (focused on Duchenne/Becker and Limb-Girdle muscular dystrophy, the Leiden Muscular Dystrophy pages)
• Muscle regeneration and differentitation
  • Development of experimentally validated computational models for muscle differentiation in health and disease
  • MyoD-induced myo-differentiation
• Meta-analysis of microarray studies on muscle development and disesase
• Therapy for muscular dystrophies
  • "Integration of two promising therapeutic approaches for Duchenne muscular dystrophy: antisense oligonucleotide-mediated gene correction and myostatin inhibition" funded by Duchenne Parent Project
  • Project coordinator: "Towards broad clinical and technological application of gene expression engineering by exon skipping" funded by SENTER (IOP Genomics programme)
  • Development of diagnostic markers and markers for disease progression "Developing mass spectrometry-based protein profiling to improve diagnosis of muscular dystrophies"  funded (2005-2007) by Prinses Beatrix Fonds
• Others
  • Xp22  -  Keratosis follicularis spinulosa decalvans (see OMIM)
    unravel the cause of KFSD, in collaboration with Prof.dr. M.H. Breuning (Clinical Genetics, LUMC, LEIDEN, Nederland) and  JC Oosterwijk (Clinical Genetics, Groningen University Medical Centre, GRONINGEN, Nederland)
  • mental retardation
    unravel the causes of mental retardation, in collaboration with Prof.dr. M.H. Breuning (Clinical Genetics, LUMC, LEIDEN, Nederland)