Edwin Cuppen

Summary

Publications

  1. pmc Genomic DNA pooling strategy for next-generation sequencing-based rare variant discovery in abdominal aortic aneurysm regions of interest-challenges and limitations
    Magdaléna Harakalová
    Department of Medical Genetics, University Medical Center Utrecht, The Netherlands
    J Cardiovasc Transl Res 4:271-80. 2011
  2. pmc Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat
    Joram D Mul
    Hubrecht Institute KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Obesity (Silver Spring) 20:612-21. 2012
  3. pmc Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classes
    Michal Mokry
    Hubrecht Institute KNAW and University Medical Center, 3584 CT Utrecht, The Netherlands
    Nucleic Acids Res 40:148-58. 2012
  4. pmc Rat traps: filling the toolbox for manipulating the rat genome
    Ruben van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genome Biol 11:217. 2010
  5. pmc Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat
    Joram D Mul
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 6:e19600. 2011
  6. pmc Systematic generation of in vivo G protein-coupled receptor mutants in the rat
    R van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences and University Medical Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands
    Pharmacogenomics J 11:326-36. 2011
  7. pmc A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability
    Jos B Poell
    Hubrecht Institute, University Medical Center Utrecht, Cancer Genomics Center, Utrecht, The Netherlands
    PLoS ONE 7:e43569. 2012
  8. pmc Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain
    Rick van Nuland
    NMR Spectroscopy Research Group, Bijvoet Center for Biomolecular Research, Utrecht University Utrecht, Padualaan 8, Utrecht, CH, 3854, The Netherlands
    Epigenetics Chromatin 6:12. 2013
  9. pmc Improving mammalian genome scaffolding using large insert mate-pair next-generation sequencing
    Sebastiaan van Heesch
    Hubrecht Institute KNAW and University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
    BMC Genomics 14:257. 2013
  10. pmc Identification of factors required for meristem function in Arabidopsis using a novel next generation sequencing fast forward genetics approach
    Michal Mokry
    Hubrecht Institute, Developmental Biology and Stem Cell Research, KNAW and University Medical Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands
    BMC Genomics 12:256. 2011

Detail Information

Publications90

  1. pmc Genomic DNA pooling strategy for next-generation sequencing-based rare variant discovery in abdominal aortic aneurysm regions of interest-challenges and limitations
    Magdaléna Harakalová
    Department of Medical Genetics, University Medical Center Utrecht, The Netherlands
    J Cardiovasc Transl Res 4:271-80. 2011
    ....
  2. pmc Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat
    Joram D Mul
    Hubrecht Institute KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Obesity (Silver Spring) 20:612-21. 2012
    ....
  3. pmc Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classes
    Michal Mokry
    Hubrecht Institute KNAW and University Medical Center, 3584 CT Utrecht, The Netherlands
    Nucleic Acids Res 40:148-58. 2012
    ..These categories are strongly enriched for genes from different functional classes. Our results demonstrate a complementary value in Pol II chip-seq and RNA-seq approaches for better understanding of gene expression regulation...
  4. pmc Rat traps: filling the toolbox for manipulating the rat genome
    Ruben van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genome Biol 11:217. 2010
    ..Here we outline the current status, possibilities and application of these techniques in the rat...
  5. pmc Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat
    Joram D Mul
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 6:e19600. 2011
    ..Thereby it provides a crucial signal by which hypothalamic neural circuits control energy balance and guide limbic brain areas to enhance motivational or incentive-related aspects of food consumption...
  6. pmc Systematic generation of in vivo G protein-coupled receptor mutants in the rat
    R van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences and University Medical Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands
    Pharmacogenomics J 11:326-36. 2011
    ..The mutants presented here may greatly benefit studies to understand specific GPCR function and support the development of novel therapeutic strategies...
  7. pmc A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability
    Jos B Poell
    Hubrecht Institute, University Medical Center Utrecht, Cancer Genomics Center, Utrecht, The Netherlands
    PLoS ONE 7:e43569. 2012
    ..Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy...
  8. pmc Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain
    Rick van Nuland
    NMR Spectroscopy Research Group, Bijvoet Center for Biomolecular Research, Utrecht University Utrecht, Padualaan 8, Utrecht, CH, 3854, The Netherlands
    Epigenetics Chromatin 6:12. 2013
    ....
  9. pmc Improving mammalian genome scaffolding using large insert mate-pair next-generation sequencing
    Sebastiaan van Heesch
    Hubrecht Institute KNAW and University Medical Center Utrecht, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
    BMC Genomics 14:257. 2013
    ..Paired-tag sequencing approaches are commonly used for the analysis of genome structure. However, mammalian genomes have a complex organization with a variety of repetitive elements that complicate comprehensive genome-wide analyses...
  10. pmc Identification of factors required for meristem function in Arabidopsis using a novel next generation sequencing fast forward genetics approach
    Michal Mokry
    Hubrecht Institute, Developmental Biology and Stem Cell Research, KNAW and University Medical Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands
    BMC Genomics 12:256. 2011
    ..Although sequencing of complete genomes now becomes available, discriminating causal mutations from the enormous amounts of background variation remains a major challenge...
  11. pmc Efficient double fragmentation ChIP-seq provides nucleotide resolution protein-DNA binding profiles
    Michal Mokry
    Cancer Genomics Center, Department of Medical Genetics, Hubrecht Institute and University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 5:e15092. 2010
    ..Although optimized for the AB/SOLiD platform, the same approach may be applied to other platforms...
  12. pmc Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals
    Ruben van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Royal Netherlands Academy of Sciences, Utrecht, The Netherlands
    BMC Genomics 9:460. 2008
    ..N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive...
  13. doi request reprint Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis
    Ruben van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Carcinogenesis 29:1290-7. 2008
    ..The MSH6 knockout rat complements existing models for studying genetic instable tumorigenesis as it provides experimental opportunities that are not available or suboptimal in current models...
  14. pmc Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates
    Bart M G Smits
    Hubrecht Laboratory, Functional Genomics Group, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    BMC Genomics 6:170. 2005
    ..Detailed knowledge on genetic variation between strains is important from a biomedical, particularly pharmacogenetic point of view and useful for marker selection for genetic cloning and association studies...
  15. doi request reprint Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ line
    Harma Feitsma
    Hubrecht Institute and Cancer Genomics Center, 3584 CT Utrecht, The Netherlands
    Mutagenesis 23:325-9. 2008
    ..Alternatively, the MMR system in the zebrafish germ line may be saturated very rapidly, thereby having a limited effect on high-dose ENU mutagenesis...
  16. pmc An ENU-mutagenesis screen in the mouse: identification of novel developmental gene functions
    Carolien Wansleeben
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Utrecht, The Netherlands
    PLoS ONE 6:e19357. 2011
    ..Here we describe a phenotype-based screen for recessive mutations affecting embryonic development...
  17. doi request reprint Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats
    Judith R Homberg
    Hubrecht Institute, Uppsalalaan 8, 3584, CT, Utrecht, The Netherlands
    Psychopharmacology (Berl) 200:367-80. 2008
    ..While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood...
  18. doi request reprint Multiplexed array-based and in-solution genomic enrichment for flexible and cost-effective targeted next-generation sequencing
    Magdaléna Harakalová
    Department of Medical Genetics, University Medical Center Utrecht, The Netherlands
    Nat Protoc 6:1870-86. 2011
    ..This protocol gives details for a single-tube procedure, but scaling to a manual or automated 96-well plate format is possible and discussed...
  19. pmc Repertoire and evolution of miRNA genes in four divergent nematode species
    Elzo de Wit
    Hubrecht Institute KNAW and University Medical Center Utrecht, Cancer Genomics Center, Utrecht 3584 CT, The Netherlands
    Genome Res 19:2064-74. 2009
    ..The identification and systematic analysis of small RNA repertoire in four nematode species described here provides a valuable resource for understanding the evolutionary dynamics of miRNA-mediated gene regulation...
  20. doi request reprint Highly Efficient ENU Mutagenesis in Zebrafish
    Ewart de Bruijn
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584, CT, Utrecht, The Netherlands
    Methods Mol Biol 546:3-12. 2009
    ..With this procedure an average germ line mutation load of one mutation every 1.0 x 10(5)-1.5 x 10(5) basepairs is reached routinely in our lab...
  21. pmc CASCAD: a database of annotated candidate single nucleotide polymorphisms associated with expressed sequences
    Victor Guryev
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
    BMC Genomics 6:10. 2005
    ..However, such information is very important for selecting the most promising and useful candidate polymorphisms for use in experimental setups...
  22. doi request reprint Zebrafish with mutations in mismatch repair genes develop neurofibromas and other tumors
    Harma Feitsma
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, Utrecht University, Utrecht, The Netherlands
    Cancer Res 68:5059-66. 2008
    ..Our findings indicate that zebrafish mimic distinct features of the human disease and are complementary to mouse models...
  23. pmc Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer
    Wigard P Kloosterman
    Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands
    Genome Biol 12:R103. 2011
    ..The significance of these clusters for tumor development or metastatic spread is largely unclear...
  24. pmc Discovery of variants unmasked by hemizygous deletions
    Ron Hochstenbach
    Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    Eur J Hum Genet 20:748-53. 2012
    ..Conceivably, inherited deletions may unmask rare pathogenic variants that may exert a phenotypic impact through a recessive mode of gene action...
  25. pmc Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing libraries
    Michal Mokry
    Hubrecht Institute and University Medical Center Utrecht, KNAW, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nucleic Acids Res 38:e116. 2010
    ..Raw sequencing data, alignment files and called SNPs have been submitted into GEO database http://www.ncbi.nlm.nih.gov/geo/ with accession number GSE18542...
  26. ncbi request reprint Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesis
    Bart M G Smits
    Hubrecht Laboratory, Utrecht, The Netherlands
    Pharmacogenet Genomics 16:159-69. 2006
    ..This study aims to provide the tools to manipulate the rat genome in a more directed way...
  27. pmc Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics
    Bart M G Smits
    Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT Utrecht, The Netherlands
    Genetics 170:1887-96. 2005
    ..In addition, we demonstrate proof of principle for the generation and cloning of human disease models in rat using ENU mutagenesis, providing good perspectives for systematic phenotypic screens in the rat...
  28. pmc Efficient target-selected mutagenesis in Caenorhabditis elegans: toward a knockout for every gene
    Edwin Cuppen
    Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
    Genome Res 17:649-58. 2007
    ..For EMS-mutagenized C. elegans, there are only approximately 500,000 NIMs. We show that a NIM genotyping approach employing high-density microarrays can, in principle, be used for the genome-wide identification of C. elegans knockouts...
  29. pmc CONREAL web server: identification and visualization of conserved transcription factor binding sites
    Eugene Berezikov
    Hubrecht Laboratory, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Nucleic Acids Res 33:W447-50. 2005
    ..Comparative analysis using different algorithms can be started by keyword without any prior sequence retrieval. The interface is available at http://conreal.niob.knaw.nl...
  30. doi request reprint Zebrafish as a cancer model
    Harma Feitsma
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cancer Res 6:685-94. 2008
    ..This review aims to provide a comprehensive overview of the state of the art of zebrafish as a model in cancer research. (Mol Cancer Res 2008;6(5):685-94)...
  31. pmc Incomplete segregation of MYH11 variants with thoracic aortic aneurysms and dissections and patent ductus arteriosus
    Magdaléna Harakalová
    Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    Eur J Hum Genet 21:487-93. 2013
    ..Furthermore, our study underscores that segregation analysis remains very important in clinical genetics. Prediction programs and mutation evaluation algorithms need to be interpreted with caution...
  32. pmc Identification of genetic modifiers of behavioral phenotypes in serotonin transporter knockout rats
    Judith Homberg
    Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands
    BMC Genet 11:37. 2010
    ..To gain insight into serotonin transporter (SERT)-specific genetic modifiers, we studied an intercross between the Wistar SERT-/- rat and the behaviorally and genetically divergent Brown Norway rat, and performed a QTL analysis...
  33. doi request reprint X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face
    Magdaléna Harakalová
    Department of Medical Genetics, University Medical Center Utrecht UMCU, Utrecht 3584 EA, The Netherlands
    J Med Genet 49:539-43. 2012
    ..Seven female relatives show a much milder expression of the phenotype...
  34. pmc Genomic and transcriptomic plasticity in treatment-naive ovarian cancer
    Marlous Hoogstraat
    Department of Medical Oncology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
    Genome Res 24:200-11. 2014
    ....
  35. pmc Genetic variation in the zebrafish
    Victor Guryev
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584CT, Utrecht, The Netherlands
    Genome Res 16:491-7. 2006
    ..Overall, the levels and organization of genetic variation between and within commonly used zebrafish strains are markedly different from other laboratory model organisms, which may affect experimental design and interpretation...
  36. pmc Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel
    Marieke Simonis
    Genome Biology Group, Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genome Biol 13:r31. 2012
    ..Recombinant inbred panels are powerful tools to study the cis and trans effects of genetic variation on molecular phenotypes such as gene expression...
  37. pmc A genome-wide SNP panel for mapping and association studies in the rat
    Isaac J Nijman
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    BMC Genomics 9:95. 2008
    ..To facilitate genetic studies like QTL mapping, genetic makers that can be easily typed, like SNPs, are essential...
  38. pmc ALK2 mutation in a patient with Down's syndrome and a congenital heart defect
    Irene C Joziasse
    Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
    Eur J Hum Genet 19:389-93. 2011
    ..These data indicate that in the context of a DS background, ALK2-mediated reduction of BMP signaling may contribute to CHDs...
  39. doi request reprint Mutagenic capacity of endogenous G4 DNA underlies genome instability in FANCJ-defective C. elegans
    Evelien Kruisselbrink
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Curr Biol 18:900-5. 2008
    ..The existence of 376,000 potentially mutagenic G4 DNA sites in the human genome could have major implications for the etiology of hereditary FancJ and nonhereditary cancers...
  40. ncbi request reprint Many inflammatory bowel disease risk loci include regions that regulate gene expression in immune cells and the intestinal epithelium
    Michal Mokry
    Division of Pediatrics, Wilhelmina Children s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
    Gastroenterology 146:1040-7. 2014
    ..These studies have focused mainly on protein-coding genes. We investigated other functional elements in the human genome, such as regulatory regions...
  41. pmc Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling
    Astrid Eijkelenboom
    Department of Molecular Cancer Research, University Medical Centre, Utrecht, The Netherlands
    Mol Syst Biol 9:638. 2013
    ..Combined, our data elucidate how FOXOs regulate gene transcription and provide insight into mechanisms by which FOXOs can induce different gene expression programs depending on chromatin architecture...
  42. doi request reprint Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms
    Wigard P Kloosterman
    Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Cell Rep 1:648-55. 2012
    ..Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements...
  43. doi request reprint A novel mutant allele of Ncx1: a single amino acid substitution leads to cardiac dysfunction
    Carolien Wansleeben
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Int J Dev Biol 54:1465-71. 2010
    ..It provides an in vivo model for this mutation and demonstrates the potential of forward genetic screens in a mammalian system...
  44. doi request reprint Serotonin transporter deficiency increases abdominal fat in female, but not male rats
    Judith R Homberg
    Functional Genomics and Bioinformatics, Hubrecht Institute, University Medical Center Utrecht, Utrecht, The Netherlands
    Obesity (Silver Spring) 18:137-45. 2010
    ....
  45. pmc Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF
    Jurian Schuijers
    Hubrecht Institute KNAW, University Medical Centre Utrecht, Utrecht, The Netherlands
    EMBO J 33:146-56. 2014
    ..Our results indicate that β-catenin is tethered to chromatin overwhelmingly through the TCF/LEF transcription factors in these three systems. ..
  46. ncbi request reprint Rat genetics: the next episode
    Bart M G Smits
    Functional Genomics Group, Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Trends Genet 22:232-40. 2006
    ..Recent developments in single nucleotide polymorphism-based genetic markers and technologies to manipulate the rat genome will undoubtedly be important tools in this next episode...
  47. pmc Single nucleotide polymorphisms associated with rat expressed sequences
    Victor Guryev
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584CT, Utrecht, The Netherlands
    Genome Res 14:1438-43. 2004
    ..Two of these "in silico-identified knockouts" reside in interesting QTL regions. Data are publicly available via a Web interface (http://cascad.niob.knaw.nl), allowing simple and advanced search queries...
  48. pmc Alkylation damage causes MMR-dependent chromosomal instability in vertebrate embryos
    Harma Feitsma
    Hubrecht Institute, Royal Academy of Arts and Sciences and University Medical Centre Utrecht, Cancer Genomics Center, 3584 CT, Utrecht, The Netherlands
    Nucleic Acids Res 36:4047-56. 2008
    ..Taken together, our results suggest that in vivo alkylation damage results in chromosomal instability and cell death due to aberrantly processed MMR-induced stalled replication forks...
  49. pmc Haplotype block structure is conserved across mammals
    Victor Guryev
    Hubrecht Laboratory, Utrecht, The Netherlands
    PLoS Genet 2:e121. 2006
    ....
  50. pmc Mammalian mirtron genes
    Eugene Berezikov
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell 28:328-36. 2007
    ..This notion is supported by our observation of several clade-specific features of mammalian and invertebrate mirtrons...
  51. pmc Cloning and expression of new microRNAs from zebrafish
    Wigard P Kloosterman
    Hubrecht Laboratory, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nucleic Acids Res 34:2558-69. 2006
    ..Most newly discovered miRNAs have low expression levels and are less conserved in other vertebrate species. Our cloning and expression analysis indicates that most abundant and conserved miRNAs in zebrafish are now known...
  52. doi request reprint Distribution and functional impact of DNA copy number variation in the rat
    Victor Guryev
    Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Centre Utrecht, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Nat Genet 40:538-45. 2008
    ..These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease...
  53. pmc Small RNA expression and strain specificity in the rat
    Sam E V Linsen
    Hubrecht Institute KNAW and University Medical Center Utrecht, Cancer Genomics Center, Utrecht, The Netherlands
    BMC Genomics 11:249. 2010
    ..We describe the expression patterns of known and novel micro (mi)RNAs and piwi-interacting (pi)RNAs...
  54. ncbi request reprint Diversity of microRNAs in human and chimpanzee brain
    Eugene Berezikov
    Hubrecht Laboratory KNAW, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Nat Genet 38:1375-7. 2006
    ..These data suggest that evolution of miRNAs is an ongoing process and that along with ancient, highly conserved miRNAs, there are a number of emerging miRNAs...
  55. pmc Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis
    Eugene Berezikov
    Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
    Genome Res 16:1289-98. 2006
    ..Most novel microRNAs candidates are not conserved beyond mammals, and ~10% are taxon-specific. Our analyses indicate that the entire microRNA repertoire is not remotely exhausted...
  56. doi request reprint Mutation discovery by targeted genomic enrichment of multiplexed barcoded samples
    Isaac J Nijman
    Hubrecht Institute, Developmental Biology and Stem Cell Research, Royal Netherlands Academy of Arts and Sciences and the University Medical Center Utrecht, Utrecht, The Netherlands
    Nat Methods 7:913-5. 2010
    ..We screened 770 genes (1.4 megabases) in thirty N-ethyl-N-nitrosourea (ENU)-mutagenized rats and identified known variants at >96% sensitivity as well as new mutations at a false positive rate < 1 in 8 megabases...
  57. pmc A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the rat
    Joram D Mul
    Hubrecht Institute KNAW and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands
    J Biol Chem 286:26781-93. 2011
    ..Although we are cautious in making a direct parallel between the presented rodent model and human disease, our data may provide new insight into the pathogenicity of recently identified human LPIN1 mutations...
  58. pmc Functional microRNA screening using a comprehensive lentiviral human microRNA expression library
    Jos B Poell
    Hubrecht Institute, Cancer Genomics Center, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    BMC Genomics 12:546. 2011
    ..Dissecting the complexities of miRNA function continues to prove challenging as miRNAs are predicted to have thousands of targets, and mRNAs can be targeted by dozens of miRNAs...
  59. doi request reprint NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral sclerosis
    Hylke M Blauw
    Department of Neurology, University Medical Center Utrecht, Heidelberglaan, Utrecht, The Netherlands
    Hum Mol Genet 21:2497-502. 2012
    ..6 years earlier. Our data show that NIPA1 polyalanine repeat expansions are a common risk factor for ALS and modulate disease course...
  60. pmc RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegans
    Ester W Frische
    Department of Physiological Chemistry, Centre for Biomedical Genetics, UMC Utrecht, Utrecht, The Netherlands
    EMBO J 26:5083-92. 2007
    ..Genetic interactions show that the RAP-1 and RAL-1/exocyst pathway also act in parallel during larval stages. Together these data provide in vivo evidence for the exocyst complex as a downstream RAL-1 effector in cell migration...
  61. ncbi request reprint Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility
    Judith R Homberg
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Eur J Neurosci 26:2066-73. 2007
    ....
  62. doi request reprint Primary colorectal cancers and their subsequent hepatic metastases are genetically different: implications for selection of patients for targeted treatment
    Joost S Vermaat
    Department of Medical Oncology, University Medical Center Utrecht, The Netherlands
    Clin Cancer Res 18:688-99. 2012
    ..Here, we analyzed genetic differences between primary colorectal adenocarcinomas (CRC) and their respective hepatic metastasis...
  63. pmc Homozygous and heterozygous p53 knockout rats develop metastasizing sarcomas with high frequency
    Ruben van Boxtel
    Hubrecht Institute for Developmental Biology and Stem Cell Research, Cancer Genomics Center, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands
    Am J Pathol 179:1616-22. 2011
    ..These unique features make this rat highly complementary to other rodent p53 knockout models and a versatile tool for investigating tumorigenesis processes as well as genotoxic studies...
  64. doi request reprint ENU mutagenesis to generate genetically modified rat models
    Ruben van Boxtel
    Hubrect Institute, NIOB KNAW, Utrecht, The Netherlands
    Methods Mol Biol 597:151-67. 2010
    ..Here, we describe the detailed protocols for ENU mutagenesis and mutant retrieval in the rat model organism...
  65. ncbi request reprint Dominant-negative ALK2 allele associates with congenital heart defects
    Kelly A Smith
    Associate Professor, Cardiac Development and Genetics Group, Hubrecht Institute for Developmental Biology and Stem Cell Research, Uppsalalaan 8, 3584 CT Utrecht, Netherlands
    Circulation 119:3062-9. 2009
    ..Despite extensive knowledge of the genetic control of AVS development, few genetic lesions have been identified that are responsible for AVS-associated congenital heart defects...
  66. ncbi request reprint Approaches to microRNA discovery
    Eugene Berezikov
    Hubrecht Laboratory, Uppsalalaan 8, 3584CT Utrecht, The Netherlands
    Nat Genet 38:S2-7. 2006
    ..How can new miRNAs be discovered and distinguished from other types of small RNA? Here we summarize current methods for identifying and validating miRNAs and discuss criteria used to define an miRNA...
  67. doi request reprint Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
    Michael A van Es
    Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands
    Ann Neurol 70:964-73. 2011
    ..We therefore investigated whether ANG variants could predispose to both ALS and PD...
  68. doi request reprint The Atp1a1 gene from inbred Dahl salt sensitive rats does not contain the A1079T missense transversion
    Michal Mokry
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Hypertension 51:922-7. 2008
    ..Although it was possible to readily detect other silent polymorphisms between SS and SR strains in the Atp1a1 gene by all methods used, no evidence for the existence of the A1079T transversion in SS/Jr rats was found...
  69. pmc Rats go genomic
    Bart M G Smits
    Functional Genomics Group, Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genome Biol 7:306. 2006
    ..A report on the meeting 'Rat Genomics and Models', Cold Spring Harbor, USA, 8-11 December 2005...
  70. pmc E2F7 represses a network of oscillating cell cycle genes to control S-phase progression
    Bart Westendorp
    Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
    Nucleic Acids Res 40:3511-23. 2012
    ..These findings provide strong evidence that E2F7 directly controls the downswing of oscillating G(1)/S genes during S-phase progression...
  71. doi request reprint Dominant missense mutations in ABCC9 cause Cantú syndrome
    Magdaléna Harakalová
    Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    Nat Genet 44:793-6. 2012
    ..Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome...
  72. doi request reprint Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline
    Wigard P Kloosterman
    Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Hum Mol Genet 20:1916-24. 2011
    ..We conclude that a similar mechanism may also drive the formation of de novo structural variation in the germline...
  73. doi request reprint Methods for small RNA preparation for digital gene expression profiling by next-generation sequencing
    Sam E V Linsen
    Hubrecht Institute, Utrecht, The Netherlands
    Methods Mol Biol 822:205-17. 2012
    ..In summary, each of these protocols has its advantages and disadvantages with respect to the ease of including barcodes, costs, and outcome...
  74. ncbi request reprint Target-selected mutagenesis of the rat
    Bart M G Smits
    Functional Genomics Group, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genomics 83:332-4. 2004
    ..We here report proof of principle for target-selected mutagenesis as a reverse genetic or knockout approach for the rat...
  75. doi request reprint Generation of genetically modified rodents using random ENU mutagenesis
    Ruben van Boxtel
    Royal Netherlands Academy of Sciences, Hubrecht Institute and University Medical Center Utrecht, Utrecht, The Netherlands
    Methods Mol Biol 693:295-308. 2011
    ..Here, we describe the detailed protocols for ENU mutagenesis and for mutant retrieval...
  76. pmc CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting
    Eugene Berezikov
    Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT, Utrecht, The Netherlands
    Genome Res 14:170-8. 2004
    ..CONREAL is accessible via a Web interface at http://conreal.niob.knaw.nl/...
  77. pmc Efficient target-selected mutagenesis in zebrafish
    Erno Wienholds
    Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genome Res 13:2700-7. 2003
    ..Furthermore,we show that TILLING can be used to detect the full spectrum of ENU-induced mutations in a vertebrate genome with the presence of many naturally occurring polymorphisms...
  78. ncbi request reprint The Wnt/beta-catenin pathway regulates cardiac valve formation
    Adam F L Hurlstone
    Netherlands Institute for Developmental Biology, Hubrecht Laboratory and Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Nature 425:633-7. 2003
    ..Our findings identify a novel role for Wnt/beta-catenin signalling in determining endocardial cell fate...
  79. doi request reprint Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation
    Victor Guryev
    Hubrecht Institute and University Medical Center Utrecht, Cancer Genomics Center, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    FEBS Lett 583:1668-73. 2009
    ....
  80. pmc Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells
    Pantelis Hatzis
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell Biol 28:2732-44. 2008
    ..The TCF4-binding regions significantly correlate with Wnt-responsive gene expression profiles derived from primary human adenomas and often behave as beta-catenin/TCF4-dependent enhancers in transient reporter assays...
  81. doi request reprint FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands
    Ewout J N Groen
    Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan, Utrecht, The Netherlands
    Arch Neurol 67:224-30. 2010
    ..To assess the frequency of FUS mutations in 52 probands with familial amyotrophic lateral sclerosis (FALS) and to provide careful documentation of clinical characteristics...
  82. doi request reprint The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats
    Johnny S W Chan
    Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan, Utrecht, The Netherlands
    J Sex Med 8:97-108. 2011
    ..Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels...
  83. ncbi request reprint Haplotype-based genetics in mice and rats
    Edwin Cuppen
    Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Trends Genet 21:318-22. 2005
    ..However, recent high-density SNP screening in commonly used mouse inbred strains reveals a complex pattern, suggesting that the current expectations for the use of haplotype blocks in genetic mapping will have to be revisited...
  84. pmc Mlh1 deficiency in zebrafish results in male sterility and aneuploid as well as triploid progeny in females
    Harma Feitsma
    Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT, Utrecht, The Netherlands
    Genetics 175:1561-9. 2007
    ..The frequency of triploid progeny of mlh1 mutant females is much higher than could be expected for random chromosome segregation. Together, these results show that multiple solutions exist for meiotic crossover/segregation problems...
  85. pmc Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats
    Judith R Homberg
    Hubrecht Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
    Psychopharmacology (Berl) 195:175-82. 2007
    ....
  86. doi request reprint Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b
    Carolien Wansleeben
    Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Development 137:1067-73. 2010
    ....
  87. doi request reprint Application of exome sequencing in the search for genetic causes of rare disorders of copper metabolism
    Sabine A Fuchs
    Department of Metabolic Diseases, University Medical Center Utrecht, 3508 AB Utrecht, The Netherlands
    Metallomics 4:606-13. 2012
    ..We anticipate that use of these novel techniques will identify the basic defect in the disorders described in this review, as well as in other genetic disorders of metal metabolism, in the next few years...
  88. pmc Genetic variation in coding regions between and within commonly used inbred rat strains
    Bart M G Smits
    Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Genome Res 14:1285-90. 2004
    ..Furthermore, we identified 17 non-synonymous SNPs that may have an effect on protein function and contribute to phenotypic differences between different laboratory strains...
  89. ncbi request reprint Serotonin transporter null mutation and sexual behavior in female rats: 5-HT1A receptor desensitization
    Eelke Snoeren
    Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands
    J Sex Med 7:2424-34. 2010
    ..Heterozygous SERT(+/-) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SERT promoter (5-HTTLPR) polymorphism...
  90. doi request reprint Disclosure of individual genetic data to research participants: the debate reconsidered
    Annelien L Bredenoord
    University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Department of Medical Ethics, Stratenum 6 131, PO Box 85500, 3508 GA Utrecht, The Netherlands
    Trends Genet 27:41-7. 2011
    ....