Genome Technology and Genetic Disease (GT&GD)
Human and Clinical Genetics - LUMC

Most recent publications

(modified last June 2010)

PhD thesis from the group

• Accepted for publication recently (ask for details)
  • Sun Y, Almomani R, Aten E, Celli J, Jaap Van Der Heijden JWF, Venselaar H, Robertson SP, Baroncini A, Franco B, Basel-Vanagaite L, Horii E, Drut R, Ariyurek Y, Den Dunnen JT, Breuning MH (2010). Terminal Osseous Dysplasia is caused by a single recurrent mutation in the FLNA gene. Am.J.Hum.Genet., in press.
  • Hestand MS, Klingenhoff A , Scherf M, Ariyurek Y, Ramos Y, Van Workum W, Suzuki M, Werner T, Van Ommen GJB, Den Dunnen JT, Harbers M, 't Hoen PAC (2010). Tissue Specic Transcript Annotation and Expression Proling with Complementary Next-generation Sequencing Technologies. Nucl. Acids Res., in press.
  • Betsalel OT, Rosenberg EH, Almeida LS, Kleefstra T, Schwartz CE, Valayannopoulos V, Abdul-Rahman O, Poplawski N, Vilarinho L, Wolf P, Den Dunnen JT, Jakobs C, Salomons GS (2010). Characterization of novel SLC6A8 variants with the use of splice-site analysis tools 
    and implementation of a newly developed LOVD database. Eur.J.Hum.Genet., in press.
  • Spitali P, Heemskerk H, Vossen RH, Ferlini A, den Dunnen JT, 't Hoen PA, Aartsma-Rus A (2010). Accurate quantification of dystrophin mRNA and exon skipping levels in Duchenne Muscular Dystrophy. Lab Invest,, E-pub ahead.
    
• Reading literature by computer - predicting protein-protein interactions
  Van Haagen HHHBM, 't Hoen PAC, Botelho Bovo A, De Morree A, Van Mulligen EM, Chichester C, Kors JA, Den Dunnen JT, Van Ommen GJB, Van Der Maarel SM, Medina Kern V, Mons B, Schuemie MJ (2009). Novel protein-protein interactions inferred from literature context. PLoS One 11:e7894.1-e7894.8.
  
• Ancestry sensitive DNA markers
  Kersbergen P, van Duijn K, Kloosterman AD, Den Dunnen JT, Kayser M, de Knijff P (2009). Developing a set of ancestry-sensitive DNA markers reflecting continental origins of humans. BMC Genetics 10:69.1-69.13.
  
• Gene variant databases
  • New reference sequence standard
    Dalgleish R, Flicek P, Cunningham F, Astashyn A, Tully RE, Proctor G, Chen Y, McLaren WM, Larsson P, Vaughan BW, Béroud C, Dobson G, Lehväslaiho H, Taschner PE, den Dunnen JT, Devereau A, Birney E, Brookes AJ, Maglott DR (2010). Locus Reference Genomic sequences: an improved basis for describing human DNA variants. Genome Med. 2: 24.1-27.7.
  • A database for L2HGDH
    Steenweg ME, Jakobs C, Errami A, van Dooren SJ, Adeva Bartolomé MT, Aerssens P, Augoustides-Savvapoulou P, Baric I, Baumann M, Bonafé L, Chabrol B, Clarke JT, Clayton P, Coker M, Cooper S, Falik-Zaccai T, Gorman M, Hahn A, Hasanoglu A, King MD, de Klerk HB, Korman SH, Lee C, Meldgaard Lund A, Mejaski-Bosnjak V, Pascual-Castroviejo I, Raadhyaksha A, Rootwelt T, Roubertie A, Ruiz-Falco ML, Scalais E, Schimmel U, Seijo-Martinez M, Suri M, Sykut-Cegielska J, Trefz FK, Uziel G, Valayannopoulos V, Vianey-Saban C, Vlaho S, Vodopiutz J, Wajner M, Walter J, Walter-Derbort C, Yapici Z, Zafeiriou DI, Spreeuwenberg MD, Celli J, den Dunnen JT, van der Knaap MS, Salomons GS (2009). An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study. Hum.Mutat. 31: 380-390.
    
• Next-generation sequencing
  • ChIP-seq - EP300 and CREBBP transcription regulation
    Ramos YF, Hestand MS, Verlaan M, Krabbendam E, Ariyurek Y, van Galen M, van Dam H, van Ommen GJ, den Dunnen JT, Zantema A, 't Hoen PAC (2010). Genome-wide assessment of differential roles for EP300 and CREBBP in transcription regulation. Nucl.Acids Res, E-pub ahead.
  • Out AA, Van Minderhout IJHM, Ariyurek Y, Tops CM, van Galen M, Goeman JJ, Taschner PEM, Schneeberger K, Ossowski S, Breuning MH, Van Ommen GJB, Den Dunnen JT, Devilee P, Hes FJ (2009). Deep-sequencing to reveal new variants in pooled DNA samples. Hum.Mutat 30: 1703-1712.
  • SNP discovery in turkey
    Kerstens HHD, Crooijmans RPMA, Veenendaal A, Dibbits BW, Chin-A-Woeng TFC, Den Dunnen JT, Groenen MAM (2009). Large scale single nucleotide polymorphism discovery in unsequenced genomes using second generation high throughput sequencing technology applied to turkey. BMC Genomics 10:479.1-479.11.
  • SNP discovery in pig
    Amaral AJ, Megens HJ, Kerstens HHD, Heuven HCM, Dibbits B, Richard PMA, Crooijmans RPMA, den Dunnen JT, Groenen MAM (2009). Application of massive parallel sequencing to whole genome SNP discovery in the porcine genome. BMC Genomics, 10: 374.1-374.10.

• Detection of sequence variants
  • High-resolution melting curve analysis (HRMA)
    • Vossen RHAM, Van Duijn M, Daha MR, Den Dunnen JT, Roos A (2010). High-throughput genotyping of mannose-binding lectin variants using high-resolution DNA-melting analysis. Hum.Mutat. 31:  E1286-E1293.
    • Pepers BA, Schut MH, Vossen RH, van Ommen GJ, den Dunnen JT, van Roon-Mom WM (2009). Cost-effective HRMA pre-sequence typing of clone libraries; application to phage display selection. BMC Biotechnol. 9: 50.1-50.6.
    •  Vossen RHAM, Aten E, Roos A, den Dunnen JT (2009). High-Resolution MeltingAnalysis (HRMA) - more than just sequence variant screening. Hum.Mutat. 30: 860-866.
    • Cost-effective and efficient point mutation detecion in DMD
      Almomani R, van der Stoep N, Bakker E, den Dunnen JT, Breuning MH, Ginjaar HB (2009). Rapid and cost effective detection of small mutations in the DMD gene by high resolution melting curve analysis. Neuromuscul.Disord. 19: 383-390.
    • Sequence-based gene expression profiling - improved robustness, resolution and reproducibility
      ’t Hoen PAC, Ariyurek Y, Thygesen HH, Vreugdenhil E, Vossen RHAM, de Menezes RX, Boer JM, van Ommen GJB, den Dunnen JT (2008). Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms. Nucl.Acids Res. 36: e141.1-141.11.
  • Detecting deletions and duplications (CNVs)
    Aten E, White SJ, Kalf ME, Vossen RHAM, Kriek M, Breuning MHB, den Dunnen JT (2008). Methods to detect CNVs in the human genome. Cytogenet.Genome Res.123: 313-321.
    
• Genetic disease
  • Tuberous Sclerosis (TSC)
    Mozaffari M, Hoogeveen-Westerveld M, Kwiatkowski D, Sampson J, Ekong R, Povey S, den Dunnen JT, van den Ouweland A, Dicky Halley H, Nellist M (2009). Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex. BMC Med.Genet. 10: 88.1-88.13.
  • Becker muscular dystrophy (BMD)
    Helderman-van den Enden AT, Straathof CS, Aartsma-Rus A, den Dunnen JT, Verbist BM, Bakker E, Verschuuren JJ, Ginjaar HB (2010). Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients. Neuromuscul.Disord. 20: 251-254.
  • Alzheimer's disease
    Liu F, Ikram MA, Janssens AC, Schuur M, de Koning I, Isaacs A, Struchalin M, Uitterlinden AG, den Dunnen JT, Sleegers K, Bettens K, Van Broeckhoven C, van Swieten J, Hofman A, Oostra BA, Aulchenko YS, Breteler MM, van Duijn CM (2009). A Study of the SORL1 Gene in Alzheimer's Disease and Cognitive Function. J.Alzheimers.Dis. 18: 51-64.
  • Duchenne and Becker muscular dystrophy
    Helderman-van den Enden AT, de Jong R, den Dunnen JT, Houwing-Duistermaat JJ, Kneppers AL, Ginjaar HB, Breuning MH, Bakker E (2009). Recurrence risk due to germline mosaicism: Duchenne and Becker muscular dystrophy. Clin.Genet. 75: 465-472.
  • Split Hand-Foot Malformation
    Aten E, den Hollander N, Ruivenkamp C, Knijnenburg J, van Bokhoven H, den Dunnen JT, Breuning MH (2009). Split Hand-Foot Malformation, Fallot's tetralogy, Mental retardation and a 1Mb 19p deletion - evidence for further heterogeneity?. Am.J.Med.Genet.A. 149A: 975-981.
    
• Exon skipping 
  Aartsma-Rus AM, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen GJ, den Dunnen JT (2009). Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum.Mutat. 30: 293-299.
  
• Collecting gene variants & guidelines
  • den Dunnen JT, Sijmons RH, Andersen PS, Vihinen M, Beckmann JS, Rossetti S, Talbot CC Jr, Hardison RC, Povey S, Cotton RG (2009). Sharing data between LSDBs and central repositories. Hum.Mutat. 30: 493-495.
  • The Human Variome Project - meeting report
    Kaput J, Cotton RG, ..., den Dunnen JT, ... and others (2009). Planning the human variome project: the Spain report. Hum.Mutat. 30: 496-510.
  • Olivier M, Petitjean A, Teague J, Forbes S, Dunnick JK, den Dunnen JT, Langerød A, Wilkinson JM, Vihinen M, Cotton RG, Hainaut P (2009). Somatic mutation databases as tools for molecular epidemiology and molecular pathology of cancer: proposed guidelines for improving data collection, distribution, and integration. Hum.Mutat. 30: 275-282.
    
• Transcription factor binding site analysis - CORE_TF
  Hestand MS, van Galen M, Villerius MP, Van Ommen GJB, Den Dunnen JT, 't Hoen PAC (2008). CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes. BMC Bioniformatics 9: 495.1-495.11.
  
• Colleting human variation - the Human Variome Project (HVP)
  Cotton RG, Auerbach AD, Axton M, Barash CI, Berkovic SF, Brookes AJ, Burn J, Cutting G, den Dunnen JT, Flicek P, Freimer N, Greenblatt MS, Howard HJ, Katz M, Macrae FA, Maglott D, Möslein G, Povey S, Ramesar RS, Richards CS, Seminara D, Smith TD, Sobrido MJ, Solbakk JH, Tanzi RE, Tavtigian SV, Taylor GR, Utsunomiya J, Watson M. (2008). GENETICS: the Human Variome Project.. Science 322: 861-862.
  
• Huntington's disease - gene expression profiling
  van Roon-Mom WMC, Pepers BA, 't Hoen PAC, Verwijmeren CACM, den Dunnen JT, Dorsman JC, van Ommen GJB (2008). Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease. BMC Mol.Biol 9: 84.1-84.13.
  
• Array analysis - reading literature by PC
  Jelier R, 't Hoen PAC, Sterrenburg E, den Dunnen JT, van Ommen GJB, Kors JA, Mons B (2008). Literature-aided meta-analysis of microarray data: a compendium study on muscle development and disease. BMC Bioinformatics 9: 291.1-291.12.
  
• Twins are not identical - consequences for CNV diagnostics
  Bruder CEG, Piotrowski A, Gijsbers ACJ, Andersson R, Erickson S, Diaz de Ståhl T, Menzel U, Sandgren J, Von Tell D, Poplawski A, Crowley M, Crasto C, Partridge EC, Tiwari H, Allison DB, Komorowski J, Van Ommen GJB, Boomsma DI, Pedersen NL, Den Dunnen JT, Wirdefeldt K, Dumanski JP (2008). Phenotypically concordant and discordant monozygotic twins display different DNA Copy-Number-Variation profiles. Am.J.Hum.Genet. 82: 763-771.
  
• A Wiki for proteins and genes    -     WikiProteins
  Mons B, Ashburner M, Chichester C, Van Mulligen E, Weeber M, Den Dunnen JT, Musen M, Cockerill M, Hermjakob H, Packer A, Pacheco R, Lewis S, Berkely A, Melton W, Barris N, Borner K, Meijssen G, Moeller E, Roes PJ, Mons A, Van Ommen GJB, Wales J, Bairoch A (2008). Calling on a million minds for community annotation in WikiProteins (why would key biology databases go Wiki?). Genome Biology 9: R89.1-89.15
  
• Retrieving micro-array datasets    -     MicroarrayRetriever
  Ivliev AE, ’t Hoen PAC, Villerius MP, den Dunnen JT, Bernd W. Brandt BW (2008). Microarray Retriever: a web-based tool for searching and large scale retrieval of public microarray data. Nucl.Acids Res., 36: W327-331.
  
• IGF1R deletion and growth
  Walenkamp MJ, de Muinck Keizer-Schrama SM, de Mos M, Kalf ME, van Duyvenvoorde HA, Boot AM, Kant SG, White SJ, Losekoot M, Den Dunnen JT, Karperien M, Wit JM. (2008). Successful long-term growth hormone therapy in a girl with haploinsufficiency of the IGF-I receptor due to a terminal 15q26.2-qter deletion detected by multiplex ligation probe amplification. J.Clin.Endocrinol.Metab. 93: 2421-2425.
  
• POMGNT1, disease and gene variation databases     -    POMGnT1 gene variation database
  Oliveira J, Soares-Silva I, Fokkema IFAC, Gonçalves A, Cabral A, Diogo L, Galán L, Guimarães A, Fineza I, Den Dunnen JT, Santos R (2008). New synonymous substitution in POMGNT1 promotes exon skipping in a CMD patient. J.Hum.Genet. 53: 565-572.
  
• Platform comparison: gene expression profiling uisng micro-arrays
  Pedotti P, 't Hoen PAC, Vreugdenhil E, Schenk GJ, Vossen RHAM, Ariyurek Y, De Hollander M, Kuiper R, Van Ommen GJB, Den Dunnen JT, Boer JM, De Menezes R (2008). Can subtle changes in gene expression be consistently detected with different microarray platforms?. BMC Genomics 9: 124.1-124.13.
  
• AON exon skipping phase I clinical trial
  Van Deutekom JCT, Janson AA, Ginjaar HB, Frankhuizen WS, Aartsma-Rus A, Bremmer-Bout M, Den Dunnen JT, Koop K, Van Der Kooi AJ, Goemans NM, De Kimpe SJ, Ekhart PF, Venneker EH, Platenburg GJ, Verschuuren JJ, Van Ommen GJB (2007). Local dystrophin restoration with antisense oligonucleotide PRO051. N.Engl.J.Med. 357: 2677-2686.
  
• Serum profiling in mdx mice
  Alagaratnam S, Mertens BJA, Dalebout JC, Deelder AM, Van Ommen GJB, Den Dunnen JT, ’t Hoen PAC (2008). Diagnosis of dystrophy in model mice by serum protein profiling. Proteomics 8: 1552-1563.
  
• Human eye colour gene
  Kayser M, Liu F, Janssens AC, Rivadeneira F, Lao O, Van Duijn K, Vermeulen M, Arp P, Jhamai MM, Van Ijcken WF, Den Dunnen JT, Heath S, Zelenika D, Despriet DD, Klaver CC, Vingerling JR, De Jong PT, Hofman A, Aulchenko YS, Uitterlinden AG, Oostra BA, Van Duijn CM (2008). Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am.J.Hum.Genet. 82: 411-423.
  
• A mouse with the human DMD gene
  't Hoen PAC, de Meijer EJ, Boer JM, Vossen RHAM, Turk R, Maatman RG, Davies KE, Van Ommen GJB, Van Deutekom JCT, Den Dunnen JT (2008). Generation and characterization of transgenic mice with the full-length human DMD gene. J.Biol.Chem. 283: 5899-5907.
  
• Prenatal diagnosis - detection technology
  Boon EMJ, Schlecht HB, Martin P, Daniels G, Vossen RHAM, Den Dunnen JT, Bakker E, Elles R (2007). Y-chromosome detection by real time PCR and Pyrophosphorolysis-Activated Polymerization using free fetal DNA isolated from maternal plasma. Prenat.Diagn. 27: 932-937.
  
• Collecting all mutations 
  • Mutation nomenclature error checking    -     Mutalyzer
    Wildeman M, Van Ophuizen E, Den Dunnen JT, Taschner PEM (2008). Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker. Hum. Mutat. 29: 6-13 
  • Cotton RG, Auerbach AD, Beckmann JS, Blumenfeld OO, Brookes AJ, Brown AF, Carrera P, Cox DW, Gottlieb B, Greenblatt MS, Hilbert P, Lehvaslaiho H, Liang P, Marsh S, Nebert DW, Povey S, Rossetti S, Scriver CR, Summar M, Tolan DR, Verma IC, Vihinen M, Den Dunnen JT (2008). Recommendations for locus-specific databases and their curation. Hum.Mutat. 29: 2-5. 
  • Cotton RG, Auerbach AD, Brown AF, Carrera P, Christodoulou J, Claustres M, Compton J, Cox DW, De Baere E, den Dunnen JT, Greenblatt M, Fujiwara M, Hilbert P, Jani A, Lehvaslaiho H, Nebert DW, Verma I, Vihinen M; Members of the Human Genome Variation Society; Human Variome Project Diagnostic Laboratory Working Group (2007). A structured simple form for ordering genetic tests is needed to ensure coupling of clinical detail (phenotype) with DNA variants (genotype) to ensure utility in publication and databases. Hum.Mutat. 28: 931-932. 
  • The Human Variome Project
    Cotton RG, 2006 Human Variome Project, Appelbe W, Auerbach AD, Becker K, Bodmer W, Boone DJ, Boulyjenkov V, Brahmachari S, Brody L, Brookes A, Brown AF, Byers P, Cantu JM, Cassiman JJ, Claustres M, Concannon P, Cotton RG, den Dunnen JT, Flicek P, Gibbs R, Hall J, Hasler J, Katz M, Kwok PY, Laradi S, Lindblom A, Maglott D, Marsh S, Masimirembwa CM, Minoshima S, de Ramirez AM, Pagon R, Ramesar R, Ravine D, Richards S, Rimoin D, Ring HZ, Scriver CR, Sherry S, Shimizu N, Stein L, Tadmouri GO, Taylor G, Watson M (2007). Recommendations of the 2006 Human Variome Project meeting. Nat.Genet. 39: 433-436.
  • Software to maintain disease-gene mutation databases
    Fokkema IFAC, Den Dunnen JT, Taschner PM (2005). LOVD: easy creation of a locus-specific sequence variation database using an "LSDB-in-a-Box" approach. Hum.Mutat., 26: 63-68. - See the Leiden Muscular Dystrophy pages.
    
• Protein studies in dysferlinopathy patients
  • Huang Y, Laval SH, van Remoortere A, Baudier J, Benaud C, Anderson LVB, Straub V, Deelder AM, Frants RR, den Dunnen JT, Bushby K, van der Maarel sm (2006). AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration. FASEB J, 21: 732-742.
  • Huang Y, Verheesen P, Roussis A, Frankhuizen W, Ginjaar I, Haldane F, Laval S, Anderson LV, Verrips T, Frants RR, de Haard H, Bushby K, den Dunnen JT, van der Maarel SM (2005). Protein studies in dysferlinopathy patients using llama-derived antibody fragments selected by phage display. Eur.J.Hum.Genet. 13: 470-474.
    
• Mutation nomenclature
  Ogino S, Gulley ML, Den Dunnen JT, Wilson RB, Association for Molecular Pathology Training and Education Committee (2007). Standard mutation nomenclature in molecular diagnostics: practical and educational challenges . J.Mol.Diagn. 9: 1-6.
  see Nomenclature for the description of sequence variations at the HGVS site.
  
• Deletions/duplications in the human genome
  • CNV in different populations
    White SJ, Vissers LELM, Geurts Van Kessel AHM, De Menezes RX, Kalay E, Lehesjoki AE, Giordano PC, Van De Vosse E, Breuning MH, Brunner HG, Den Dunnen JT, Veltman JA (2007). Variation of CNV distribution in five different ethnic populations. Cytogenet.Genome Res. 118: 19-30.
  • Combining MLPA and arrayCGH
    Van Tintelen JP, Tio RA, Kerstjens-Frederikse WS, Van Berlo JH, Boven LG, Suurmeijer AJH, White SJ, Den Dunnen JT, Te Meerman GJ, Vos YJ, van der Hout AH, Osinga J, Van Den Berg MP, Van Veldhuisen DJ, Buys CHCM, Hofstra RM, Pinto YM (2007). Severe myocardial fibrosis caused by a deletion of the 5’ end of the lamin A/C gene. J.Am.Coll.Cardiol. 49: 2430-2439.
  • Combining MLPA and arrayCGH
    Kriek M, Knijnenburg J, White SJ, Rosenberg C, den Dunnen JT, van Ommen GJB, Tanke HJ, Breuning MH, Szuhai K (2007). Diagnosis of genetic abnormalities indevelopmentally delayed patients: a new strategy combining MLPA and array-CGH. Am.J.Med.Genet.A 143: 610-614.
  • Methodology
    Den Dunnen JT, White SJ (2006). UNIT 7.14 MLPA and MAPH: sensitive detection of deletions and duplications. Current Protocols in Human Genetics, 7.14.1-7.14.20.
  • Kriek M, White SJ, Szuhai K, Knijnenburg J, van Ommen GJB, den Dunnen JT, Breuning MH (2006). Copy number variation in regions flanked (or unflanked) by duplicons among patients with developmental delay and/or congenital malformations; detection of reciprocal and partial Williams Beuren duplications. Eur.J.Hum.Genet. 14: 180-189.
  • Rosenberg C, Knijnenburg J, Bakker E, Vianna-Morgante A, Sloos WC, Otto PA, Kriek M, Hansson K, Krepisch-Santos AC, Fiegler H, Carter NP, Bijlsma EK, van Haeringen A, Szuhai K, Tanke HJ (2006). Array-CGH detection of micro rearrangements in mentally retarded individuals: clinical significance of imbalances present both in affected children and normal parents. J.Med.Genet., 43: 180-186.
    
• Genetic defect in Peter's Plus syndrome identified
  • Lesnik Oberstein SAJ, Kriek M, White SJ, Kalf ME, Szuhai K, Dunnen JT, Breuning MH, Hennekam RCM (2006). Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am.J.Hum.Genet. 79: 562-566.
    B3GALTL sequence variation database.
    
• Antibody technology
  • Verheesen P, Roussis A, de Haard HJ, Groot AJ, Stam JC, den Dunnen JT, Frants RR, Verkleij AJ, Theo Verrips C, van der Maarel SM (2006). Reliable and controllable antibody fragment selections from camelid non-immune libraries for target validation. Biochim.Biophys.Acta, 1764: 1307-1319.
    
• Rearrangements in the DMD gene
  • Aartsma-Rus A, Van Deutekom JCT, Fokkema IF, Van Ommen GJB, Den Dunnen JT (2006). Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve, 34: 135-144.
    see also: DMD sequence variation database.
  • White SJ, Aartsma-Rus A, Flanigan KM, Weiss RB, Kneppers, ALJ, Lalic T, Janson AAM, Ginjaar HB, Breuning MH, den Dunnen JT (2006). Duplications in the DMD gene. Hum.Mutat., 27: 938-945.
    see also: DMD deletion/duplication database.
  • White SJ, den Dunnen JT (2006). Copy number variation in the genome; the human DMD gene as an example. Cytogenet. Genome Res., 115: 240-246.
    
• Gene expression profiling in muscular dystrophy
  • data analysis
    Vinciotti V, Liu X, Turk R, De Meijer EJ, 't Hoen PAC (2006). Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data. BioInformatics 7: 183.1-183.12.
  • myogenesis
    Sterrenburg E, van der Wees CSC, White SJ, Turk R, de Menezes RX, van Ommen GJB, den Dunnen JT, 't Hoen PAC (2006). Gene expression profiling highlights defective myogenesis in DMD patients and a possible role for bone morphogenetic protein 4. Neurobiol. Dis. 23: 228-236.
  • monitoring AON treatment
    ’t Hoen PAC, van der Wees CGC, Aartsma-Rus A, Turk R, Goyenvalle A, Danos O, Garcia L, van Ommen GJB, den Dunnen JT, van Deutekom JCT (2006). Gene expression profiling to monitor therapeutic and adverse effects of antisense therapies for Duchenne Muscular Dystrophy. Pharmacogenomics 7: 281-297.
    
• Exploring the frontiers of therapeutic exon skipping
  Aartsma-Rus A, Kaman WE, Weij R, den Dunnen JT, van Ommen GJB, van Deutekom JCT  (2006). Exploring the frontiers of therapeutic exon skipping for Duchenne Muscular Dystrophy. Molecular Therapy, 14: 401-407.
  
• A complex chromosome 22 rearrangement
  Kriek M, Szuhai K, Kant S, White SJ, Dauwerse JG, Fiegler H, Carter NP, Knijnenburg J, den Dunnen JT, Tanke H, Breuning MH, Carla Rosenberg C (2006). A complex rearrangement on chromosome 22 affecting both homologues; haplo-insufficiency of the Cat eye critical region has no clinical relevance. Human Genetics, 120: 77-84.
  
• Huntington's disease
  • Cong SY, Pepers BA, Roos RAC, van Ommen GJB, Dorsman JC (2005). Small N-terminal mutant huntingtin fragments, but not wild type, are mainly present in monomeric form: implications for pathogenesis. Exp.Neurol. 199: 257-264.
  • Cong SY, Pepers BA, Roos RAC, van Ommen GJB, Dorsman JC (2005). Epitope mapping of monoclonal antibody 4C8 recognizing the protein huntingtin. Hybridoma (Larchmt) 24: 231-235.
  • Cong SY, Pepers BA, Evert BO, Rubinsztein DC, Roos RAC, van Ommen GJB, Dorsman JCT (2005). Mutant huntingtin represses CBP, but not p300, by binding and protein degradation. Mol.Cell.Neurosci. 30: 12-23.
    
• Gene expression profiling
  • Prorenin in cardiomyocytes
    Saris JJ, 't Hoen PAC, Garrelds IM, Dekkers DH, den Dunnen JT, Lamers JM, Danser JAH (2006). Prorenin induces intracellular signaling in cardiomyocytes independently of angiotensin II. Hypertension 48: 564-571.
  • comparing neuromuscular disorder animal models
    Turk R, Sterrenburg E, van der Wees CGC, de Meijer EJ, de Menezes RX, Groh S, Campbell KP, Noguchi S, van Ommen GJB, den Dunnen JT, 't Hoen PAC (2006). Common pathological mechanisms in mouse models for muscular dystrophies. FASEB Journal, 20: 127-129.
  • gene expression profiling in neuroblastoma  (facilitated by the LGTC)
    de Ruijter AJ, Meinsma RJ, Bosma P, Kemp S, Caron HN, van Kuilenburg AB (2005). Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma. Exp.Cell Res. 309: 451-467. 
  • micro-array data analysis - time series
    Tucker A, Vinciotti V, 't Hoen PAC, Liu X (2005). Bayesian network classifiers for time-series microarray data. In: IDA 2005 (Ed. Famili AF et al.). Springer Verlag Berlin, Heidelberg, pp. 475-485.
  • mdx over time
    Turk R, Sterrenburg E, de Meijer EJ, van Ommen GJB, den Dunnen JT and 't Hoen PAC (2005). Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling. BMC Genomics, 6: 98.1-98.15.
    
• Methodology
  Den Dunnen JT, Beggs, AH (2006). UNIT 9.3 Multiplex PCR for identifying DMD gene deletions. Current Protocols in Human Genetics, 9.3.1-9.3.22.
  
• Exon skipping 
  Aartsma-Rus A, de Winter CL, Janson AAM, Kaman WE, van Ommen GJB, den Dunnen JT, van Deutekom JCT (2006). Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping: indication for steric hindrance of SR protein binding sites. Oligonucleotides 15: 284-297.
  
• Review: genome-wide studies in nutrition research 
  Corthésy-Theulaz I, den Dunnen JT, Ferré, P, Geurts JMW, Müller M, van Belzen N, van Ommen B (2005). Nutrigenomics: the impact of biomics technology on nutrition research. Ann.Nutr.Metab. 49: 355-365.
  
• Detecting deletions and duplications in genomic DNA
  • Copy number variation in the human genome
    Van Ommen GJB (2005). Frequency of new copy number variation in humans. Nat.Genet. 37: 333-334. 
  • MLPA detection of deletions/duplications in the DMD-gene
    Lalic T, Vossen RHAM, Coffa J, Schouten J, Guc-Scekic M, Radivojevic D, Djurisic M, Breuning MH, White SJ, den Dunnen JT (2005). Deletion and duplication screening in the DMD gene using MLPA. Eur.J.Hum.Genet., 13: 1231-1234.
  • Deletions/duplication in the alpha- and beta-globin gene clusters
    Harteveld CL, Voskamp A, Phylipsen M, Akkermans N, Den Dunnen JT, White SJ, Giordano PC (2005). High resolution characterization of 16p13.3 and 11p15.4 rearrangements causing alpha- and beta-thalassemia by three-color Multiplex Ligation-Dependent Probe Amplification. J.Med.Genet. 42: 922-931..
  • Deletions in sarcoglycan genes
    White SJ, Uitte de Willige S, Verbove D, Politano L, Ginjaar I, Breuning MH, den Dunnen JT. (2005). Sarcoglycanopathies and the risk of undetected deletion alleles in diagnosis. Hum.Mutat. 26: 59.1-59.7.
  • Analysis EXT1 and EXT2 genes in multiple osteochondromas
    Vink GR, White SJ, Gabelic S, Hogendoorn PC, Breuning MH, Bakker E (2005). Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations. Eur.J.Hum.Genet. 13: 470-474.
  • Mutation screening in RSTS
    Roelfsema JH, White SJ, Ariyürek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, Den Dunnen JT, Van Ommen GJB, Breuning MH, Hennekam RCM, Peters DJM (2005). Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in the CBP and EP300 gene are both disease causing. Am.J.Hum.Genet. 76: 572-580.
  • Methodology - MAPH / MLPA
    White SJ, Breuning MH and den Dunnen JT (2004). Detecting copy number changes in genomic DNA: MAPH and MLPA. In: Cytometry, 4^th Edition, Methods in Cell Biology, Ch32: 751-768.
  • Two-colour MLPA
    White SJ, Vink GR, Kriek M, Wuyts W, Schouten J, Bakker E, Breuning MH, Den Dunnen JT (2004).Two-colour MLPA; detecting genomic rearrangements in hereditary multiple exostoses. Hum.Mutat., 24: 86-92.
    
• Array-based mutation detection: blood-group typing
  Beiboer SHW, Wieringa-Jelsma T, Maaskant-Van Wijk PA, Van Der Schoot E, Van Zwieten R, Roos D, Den Dunnen JT, De Haas M (2005). Rapid genotyping of blood group antigens by multiplex PCR and DNA microarray. Transfusion, 45: 667-679.
  
• Exon-skipping gene therapy in DMD - review
  van Deutekom JCT (2005). The 'pro-sense' approach to Duchenne muscular dystrophy. Eur.J.Hum.Genet. 13: 518-519.
  
• FRG2 upregulated in FSHD
  Rijkers T, Deidda G, van Koningsbruggen S, van Geel M, Lemmers RJ, van Deutekom JCT, Figlewicz D, Hewitt JE, Padberg GW, Frants RR, van der Maarel SM (2004). FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating primary myoblast cultures of FSHD patients. J.Med.Genet. 41: 826-836.
  
• Mutation detection in the DMD gene
  • Dent KM, Dunn DM, von Niederhausern AC, Kerr L, Bromberg MB, Tuohy T, White SJ, Den Dunnen JT, Weiss RB, Flanigan KM (2005). Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am.J.Med.Genet. 134: 295-298.
  • Buzin CH, Feng J, Yan J, Scaringe W, Liu Q, Den Dunnen JT, Mendell JR, Sommer SS (2005). Mutation rates in the dystrophin gene: A hotspot of mutation at a CpG dinucleotide. Hum.Mutat. 25: 177-188.
    
• BioInformatics - micro-array data analysis
  • Boer JM (2005). Microarrays in colorectal cancer. In: Encyclopedic reference of genomics and proteomics in molecular medicine (Eds. Lehrach H and Ruiz P), Springer Verlag, in press. 
  • de Menezes RX, Boer JM, van Houwelingen JC (2004). Microarray data analysis: a hierarchical t-test to handle heteroscedasticity. Applied Bioinformatics, 3: 229-235.
    
• ArrayCGH on laser capture microdissected samples
  Cardoso J, Molenaar L, de Menezes RX, Rosenberg C, Morreau H, Moslein G, Fodde R, Boer JM (2004). Genomic profiling by DNA amplification of laser capture microdissected tissues and array CGH. Nucl.Acids Res. 32: e146.1-146.13.

• Limited gene expression variation in muscle from different mouse strains
  Turk R, 't Hoen PAC, Sterrenburg E, de Menezes RX, de Meijer EJ, Boer JM, van Ommen GJB and Jden Dunnen JT (2004). Gene expression variation between mouse inbred strains. BMC Genomics 5: 57.
  
• Myoblast differentiation
  Sterrenburg E, Turk R, 't Hoen PAC, Van Deutekom JCT,  Boer JM, Van Ommen GJB,  Den Dunnen JT (2004). Large-scale gene expression analysis of human skeletal myoblast differentiation. Neuromuscul Disord. 14: 507-518.
  
• Large copy number variations in the human genome
  Fredman D, White SJ, Potter S, Eichler EE, Dunnen JT, Brookes AJ (2004). Complex SNP-related sequence variation in segmental genome duplications. Nat.Genet. 36: 861-866.
  
• Exon skipping in a mouse with a human DMD-gene
  M Bremmer-Bout, A Aartsma-Rus, EJ de Meijer, WE Kaman, AAM Janson, RHAM Vossen, GJB van Ommen, JT den Dunnen, and JCT van Deutekom (2004). Targeted exon skipping in transgenic hDMD mice: a model for direct pre-clinical screening of human-specific antisense oligonucleotides. Mol.Ther. 10: 232-240.
  
• Antisense exon skipping technology
  A Aartsma-Rus, WE Kaman, M Bremmer-Bout, AAM Janson, JT den Dunnen, GJB van Ommen and JCT van Deutekom (2004). Comparative analysis of antisense oligonucleotide analogs for targeted DMD exon 46 skipping in muscle cells. Gene Ther. 11: 1391-1398.
  
• Gene expression profiling in leukemia   (facilitated by the LGTC)
  Valk PJ, Verhaak RG, Beijen MA, Erpelinck CA, Barjesteh van Waalwijk van Doorn-Khosrovani S, Boer JM, Beverloo HB, Moorhouse MJ, van der Spek PJ, Lowenberg B, Delwel R. (2004). Prognostically useful gene-expression profiles in acute myeloid leukemia. N.Engl.J.Med. 350: 1617-1628.
  
• Array-based mutation screening
  Van Moorsel CHM, Van Wijngaarden EE, Fokkema IFAC, Den Dunnen JT, Roos D, Van Zwieten R, Giordano PC, Harteveld CL (2004). beta-Globin mutation detection by tagged single-base extension and hybridisation to universal glass and flow-through microarrays. Eur.J.Hum.Genet., 12: 567-573.
  
• Deletions/duplications in mental retardation
  Kriek M, White SJ, Bouma MC, Dauwerse JG, Hansson KBM, Nijhuis JV, Bakker E, Van Ommen GJB, Den Dunnen JT, Breuning MH (2004). Genomic balances in mental retardation. J.Med.Genet. 41: 249-255.
  
• BioInformatics - gene expression array data analysis
  't Hoen PAC, Turk R, Boer JM, Sterrenburg E, de Menezes RX, van Ommen GJB and den Dunnen JT (2004). Intensity-based analysis of two-colour microarrays enables efficient and flexible hybridisation designs. Nucl.Acids Res. 32: e41.1-e41.6.
  
• The DGC in Drosophila
  LC Dekkers, MC van der Plas, PB van Loenen, JT den Dunnen, GJB van Ommen, LG Fradkin, JN Noordermeer (2004). Embryonic expression patterns of the Drosophila Dystrophin Glycoprotein Complex orthologs. Gene Expr.Patterns 4: 153-159.
  
• Noninvasive diagnosis in 96% of DMD patients
  J Yan, J Feng, CH Buzin, W Scaringe, Q Liu, JR Mendell, JT den Dunnen, SS Sommer (2004). Three-tiered noninvasive diagnosis in 96% of patients with Duchenne muscular dystrophy(DMD). Hum.Mutat. 23: 203-204.
  
• Targeted multiple exons skipping in cultured DMD-cells
  Aartsma-Rus, AAM Janson, WE Kaman, M Bremmer-Bout, GJB van Ommen, JT den Dunnen and JCT van Deutekom (2004). Antisense-induced multi-exon skipping for DMD makes more sense. Am.J.Hum.Genet. 74: 83-92.
  
• BioInformatics - gene expression array data analysis
  J Goeman, SA van de Geer, Floor de Kort, HC van Houwelingen (2004). A global test for groups of genes: testing association with a clinical outcome. BioInformatics 20: 93-99.
  
• Point mutation detection in the DMD-gene: DGGE
  Hofstra RMW, Mulder IM, Vossen RHAM, de Koning-Gans PAM, Kraak M, Ginjaar HB, van der Hout AH, Bakker E, Buys CHCM, van Ommen GJB, van Essen AJ, den Dunnen JT (2004). Whole gene DGGE-based mutation scanning of the dystrophin gene in DMD/BMD patients. Hum.Mutat. 23: 57-66.
  
• Review on DMD gene therapy
  Van Deutekom JCT and Van Ommen GJB. Advances in Duchenne Muscular Dystrophy gene therapy (2003). Nature Rev.Genet. 4:  774-784.
  
• Technology - Aggregation of embryonic stem cells
  Maatman R, Gertsenstein M, de Meijer E, Nagy A, Vintersten K (2003). Aggregation of embryos and embryonic stem cells. Methods Mol.Biol. 209: 201-230.
  
• MAPH as alternative for FISH
  White SJ, van Ommen GJB, den Dunnen JT and Breuning MH (2003). An alternative for FISH - detecting deletion and duplication carriers within 24 hours. J.Med.Genet. 40: e113.1-e113.4.
  
• OPMD
  Van Koningsbruggen S, de Haard H, de Kievit P, Dirks RW, van Remoortere A, Groot AJ, van Engelen BG, den Dunnen JT, Verrips CT, Frants RR, van der Maarel SM (2003). Llama-derived phage display antibodies in the dissection of the human disease oculopharyngeal muscular dystrophy. J.Immunol.Methods 279: 149-161.
  
• Mosaicism in DMD; germline and somatic
  Essen AJ, Mulder IM, Vlies Pv P, Hout AH, Buys CH, Hofstra RM, Dunnen JT (2003). Detection of point mutation in dystrophin gene reveals somatic and germline mosaicism in the mother of a patient with Duchenne muscular dystrophy. Am.J.Med.Genet. 118A: 296-298.
  
• Describing sequence variants  (see also Human Genome Variation Society)
  JT den Dunnen, MH Paalman MH (2003). Standardizing mutation nomenclature: why bother ?. Hum.Mutat. 22: 181-182.
  
• GeneHopper: linking genes across species and platforms
  Svensson BAT, Kreeft AJ, van Ommen GJB, den Dunnen JT, Boer JM (2003). GeneHopper: a web-based search engine to link gene expression platforms through GenBank accession numbers. Genome Biology 4: R35.
  
• Targeted exon skipping in cultured cells of DMD-patients
  Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, den Dunnen JT, Baas F, van Ommen GJ, van Deutekom JCT (2003). Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients. Hum.Mol.Genet. 12: 907-914.
  
• Fluorescent amino-allyl labelling of cRNA
  't Hoen PAC, de Kort F, van Ommen GJB, den Dunnen JT (2003). Fluorescent labelling of cRNA for microarray applications. Nucl.Acids Res. 31: e20.1-e20.8
  
• A common reference for cDNA microarray hybridizations
  Sterrenburg et al. (2002). A common reference for cDNA microarray hybridizations. Nucl.Acids Res.30: e116.1-e.116.6.
  
• MAPH for improved deletion/duplication detection in the DMD-gene
  White S et al. (2002) Comprehensive detection of genomic duplications and deletions in the DMD gene, by use of multiplex amplifiable probe hybridization. Am.J.Hum.Genet. 71: 365-374.
  
• Targeted exon skipping in the DMD-gene
  Aartsma-Rus A et al. (2002) Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy. Neuromuscul Disord. 12: S71.
  
• Toxicity of expanded single-amino-acid stretches 
  Dorsman JC et al. (2002) Strong aggregation and increased toxicity of polyleucine over polyglutamine stretches in mammalian cells. Hum.Mol.Genet. 11: 1487-1496.
  
• Expression profiling in mdx-muscle
  Boer JM et al (2002) Expression profiling in stably regenerating skeletal muscle of dystrophin-deficient mdx mice. Neuromuscul.Disord. 12: S118.
  
• Improved cloning of long trinucleotide repeat sequences
  Dorsman JC, Bremmer-Bout M, Pepers B, van Ommen GJB, den Dunnen JT (2002) Interruption of perfect CAG repeats by CAA triplets significantly improves the stability of glutamine-encoding repeat sequences. BioTechniques 33: 976-978.
  
• Long-term persistence of donor nuclei in a DMD patient 
  Gussoni E et al. (2002). Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J.Clin.Invest. 110: 807-814.
  
• The dystrophin gene and DMD / BMD - a mini review
  Den Dunnen JT et al. (2002) Het dystrofine gen, betrokken bij Duchenne en Becker spierdystrofie. Ned.Tijdschr.Geneesk. 146: 364-367. 
  
• Point mutation detection in the DMD-gene: DHPLC
  Bennett RR et al. (2001) Detection of mutations in the dystrophin gene via automated DHPLC screening and direct sequencing. BMC Genet. 2: 17.
  
• Detecting point mutations in the DMD-gene
  Den Dunnen JT (2001) Point mutation detection in the dystrophin gene. In: Bushby KMD, Anderson LVB (eds.). Muscular Dystrophy; methods and protocols. Humana Press, Totowa, pp. 85-109. 
   
• New adenoviral vectors - improved myoD-induced in vitro myogenesis
  Havenga MJ et al (2002) Exploiting the natural diversity in adenovirus tropism for therapy and prevention of disease. J.Virol. 76: 4612-4620.
  
• WHSC1L1, a new gene closely resembling WHSC1
  Stec eI t al. (2001) WHSC1L1, a gene on human chromosome 8p11.2, closely resembles the WHSC1 gene and maps to a duplicated region shared with 4p16.3. Genomics 76: 5-8. 
  
• Mutation nomenclature
  Den Dunnen JT & Antonarakis SE (2001) Nomenclature for the description of human sequence variations. Hum.Genet. 109: 121-124.
  
• Restoration of dystrophin expression in DMD patient cells
  Van Deutekom JCT et al. (2001) Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum.Mol.Genet. 10: 1547-1554.
  
• Exon trapping
  Wapenaar MC and Den Dunnen JT (2001) Exon trapping. Application of a large-insert multiple-exon-trapping system. Methods Mol.Biol. 175: 201-215.
  
• The PWWP protein domain: for protein-protein interaction ?
  Stec I et al. (2001) The PWWP domain: a potential protein-protein interaction domain in nuclear proteins influencing differentiation? FEBS Lett. 473: 1-5.
  
• Nonsense mutation in Becker patient
  Ginjaar HB et al. (2000) Dystrophin nonsense mutation induces different levels of exon 29 skipping and leads to variable phenotypes within one BMD family. Eur.J.Hum.Genet.8: :793-796.
  
• Mutation nomenclature
  Den Dunnen JT & Antonarakis SE (2000) Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum.Mutat.15: 7-12.
  
• Making muscle cells for (prenatal) diagnosis
  Roest PA et al. (1999) New possibilities for prenatal diagnosis of muscular dystrophies: forced myogenesis with an adenoviral MyoD-vector. Lancet 353 (9154): 727-728.
  
• Protein Truncation Test
  den Dunnen JT & Van Ommen GJB (1999) The protein truncation test: A review. Hum Mutat. 14: 95-102.
  
• Mutation detection in Emery-Dreifuss muscular dystrophy (EMD)
  De Koning Gans et al. (1999) A protein truncation test for Emery-Dreifuss muscular dystrophy (EMD): detection of N-terminal truncating mutations. Neuromuscul Disord. 9: 247-250.

PhD thesis from the group

• Ellen Sterrenburg (2007) - Application of microarray-based gene expression profiling technology to neuromuscular disorders
• Rolf Turk (2006) - Molecular mechanisms in muscular dystrophy : a gene expression profiling study
• Yanchao Huang (2006) - Molecular dissection of the dysferlin protein complex in skeletal muscle
• Stefan White (2006) - Detecting copy number changes in genomic DNA - MAPH and MLPA
• Shuyan Cong (2006) - 
• Annemieke Aartsma-Rus (2005) - Development of an antisense-mediated exon skipping therapy for Duchenne Muscular Dystrophy
• Pauline Roest (1997) - Development and use of the protein truncation test and forced myo-differentiation in the study and diagnosis of muscular dystrophy

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