Research Topics
Genomes and Genes | Edwin CuppenSummaryAffiliation: Netherlands Institute of Ecology Country: The Netherlands Publications
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Detail Information
Publications
Generation of medaka gene knockout models by target-selected mutagenesisYoshihito Taniguchi
Department of Radiation Genetics, CREST, Japan Science and Technology Laboratory, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
Genome Biol 7:R116. 2006..The current cryopreserved resource is expected to contain knockouts for most medaka genes...
Rats go genomicBart 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...
Efficient target-selected mutagenesis in Caenorhabditis elegans: toward a knockout for every geneEdwin 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...
Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidatesBart 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...
Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesisRuben 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...
Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesisBart M G Smits
Hubrecht Laboratory, Utrecht, The Netherlands
Pharmacogenet Genomics 16:159-69. 2006..The resulting induced rat models will be powerful tools for studying many aspects of a wide variety of human diseases...
Mismatch repair deficiency does not enhance ENU mutagenesis in the zebrafish germ lineHarma 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...
CASCAD: a database of annotated candidate single nucleotide polymorphisms associated with expressed sequencesVictor 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...
Highly Efficient ENU Mutagenesis in ZebrafishEwart 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...
Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing librariesMichal 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...
Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout ratsJudith 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...
Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward geneticsBart 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...
CONREAL web server: identification and visualization of conserved transcription factor binding sitesEugene 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...
Zebrafish as a cancer modelHarma 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)...
Single nucleotide polymorphisms associated with rat expressed sequencesVictor 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...
Identification of genetic modifiers of behavioral phenotypes in serotonin transporter knockout ratsJudith 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...
Mammalian mirtron genesEugene 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...
Haplotype block structure is conserved across mammalsVictor Guryev
Hubrecht Laboratory, Utrecht, The Netherlands
PLoS Genet 2:e121. 2006....
Genetic variation in the zebrafishVictor 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...
Rat genetics: the next episodeBart 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...
Distribution and functional impact of DNA copy number variation in the ratVictor 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...
Rat traps: filling the toolbox for manipulating the rat genomeRuben 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...
A genome-wide SNP panel for mapping and association studies in the ratIsaac 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...
Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysisEugene 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...
A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodystrophy in the ratJoram 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...
Diversity of microRNAs in human and chimpanzee brainEugene 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...
Dominant-negative ALK2 allele associates with congenital heart defectsKelly 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...
Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibilityJudith R Homberg
Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Eur J Neurosci 26:2066-73. 2007....
Cloning and expression of new microRNAs from zebrafishWigard 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...
Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classesMichal 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...
Mutagenic capacity of endogenous G4 DNA underlies genome instability in FANCJ-defective C. elegansEvelien 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...
Genetic variation in coding regions between and within commonly used inbred rat strainsBart 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...
Approaches to microRNA discoveryEugene 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...
Efficient target-selected mutagenesis in zebrafishErno 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...
GENOTRACE: cDNA-based local GENOme assembly from TRACE archivesEugene Berezikov
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
Bioinformatics 18:1396-7. 2002..AVAILABILITY: The package and examples of output files can be downloaded from http://rat.niob.knaw.nl/GENOTRACE..
Identification of factors required for meristem function in Arabidopsis using a novel next generation sequencing fast forward genetics approachMichal 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...
The Atp1a1 gene from inbred Dahl salt sensitive rats does not contain the A1079T missense transversionMichal 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...
Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animalsRuben 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...
Target-selected mutagenesis of the ratBart 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...
The Wnt/beta-catenin pathway regulates cardiac valve formationAdam 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...
Mlh1 deficiency in zebrafish results in male sterility and aneuploid as well as triploid progeny in femalesHarma 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...
Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variationVictor Guryev
Hubrecht Institute and University Medical Center Utrecht, Cancer Genomics Center, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
FEBS Lett 583:1668-73. 2009....
CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprintingEugene 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/...
Haplotype-based genetics in mice and ratsEdwin 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...
Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cellsPantelis 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...
Functional microRNA screening using a comprehensive lentiviral human microRNA expression libraryJos 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...
Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent ratsJudith R Homberg
Hubrecht Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands
Psychopharmacology (Berl) 195:175-82. 2007....
The microRNA-producing enzyme Dicer1 is essential for zebrafish developmentErno Wienholds
Department of Functional Genomics, Hubrecht Laboratory, 3584 CT Utrecht, The Netherlands
Nat Genet 35:217-8. 2003..This resulted in developmental arrest around day 10. These results indicate that miRNA-producing Dicer1 is essential for vertebrate development...
Hyperactivation of the G12-mediated signaling pathway in Caenorhabditis elegans induces a developmental growth arrest via protein kinase CAlexander M van der Linden
Hubrecht Laboratory, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Curr Biol 13:516-21. 2003..elegans. Taken together, our findings provide a potential molecular mechanism for the transforming capability of G(12) proteins...
Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24bCarolien Wansleeben
Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Development 137:1067-73. 2010....
Phylogenetic shadowing and computational identification of human microRNA genesEugene Berezikov
Cell 120:21-4. 2005..Taken together, these results suggest the presence of significantly higher numbers of miRNAs in the human genome than previously estimated...
Exploring conservation of transcription factor binding sites with CONREALEugene Berezikov
Hubrecht Laboratory
Methods Mol Biol 395:437-48. 2007..The web tool is particularly suited for the analysis of individual genes or genomic regions, although the underlying algorithm can also be used in high-throughput promoter analysis...
Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1Marcelo C Leal
Science Faculty, Department Biology, Section Endocrinology and Metabolism, Utrecht University, Kruyt Building, Room Z 203, Padualaan 8, NL 3584 CH Utrecht, The Netherlands
Cell Tissue Res 332:133-9. 2008....
Zebrafish with mutations in mismatch repair genes develop neurofibromas and other tumorsHarma 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...
Progress and prospects in rat genetics: a community viewTimothy J Aitman
Medical Research Council Clinical Sciences Centre and Imperial College London, Du Cane Road, London W12 0NN, UK
Nat Genet 40:516-22. 2008..Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research...
Alkylation damage causes MMR-dependent chromosomal instability in vertebrate embryosHarma 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...
SNP and haplotype mapping for genetic analysis in the ratKathrin Saar
Max Delbruck Center for Molecular Medicine, Robert Rossle Strae 10, 13125 Berlin, Germany
Nat Genet 40:560-6. 2008..We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies...
Blood pressure in mutant rats lacking the 5-hydroxytryptamine transporterJudith Homberg
Hypertension 48:e115-6; author reply e117. 2006
RAP-1 and the RAL-1/exocyst pathway coordinate hypodermal cell organization in Caenorhabditis elegansEster 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...
Stress-induced hyperthermia and basal body temperature are mediated by different 5-HT(1A) receptor populations: a study in SERT knockout ratsJocelien D A Olivier
Department Cognitive Neuroscience Psychoneuropharmacology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Eur J Pharmacol 590:190-7. 2008..It is concluded that the SERT knockout rat reveals that 5-HT(1A) receptors modulating stress-induced hyperthermia belong to a population of receptors that differs from that involved in hypothermia...
Serotonin transporter dosage modulates long-term decision-making in rat and humanJudith R Homberg
Department of Cognitive Neuroscience, Donders Centre for Neuroscience, UMC St Radboud, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands
Neuropharmacology 55:80-4. 2008....
Mouse microRNA profiles determined with a new and sensitive cloning methodShuji Takada
Division of Functional Genomics, Jichi Medical University, 3311 1 Yakushiji, Shimotsukeshi, Tochigi 329 0498, Japan
Nucleic Acids Res 34:e115. 2006..Our data thus indicate that the total number of miRNAs in vertebrates is larger than previously appreciated and that the expression of these molecules is tightly controlled in a tissue- and developmental stage-specific manner...
