Research Groups

Genome Structure Ageing

The primary interest of the group led by Victor Guryev is to study structural changes of genome and their role in ageing.
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    Position

    Group Leader of the Laboratory of Genome Structure and Ageing

    Research fields

    Genomics, Bioinformatics

    PhD Students
    Tristan de Jong
  • It is well known that diseases acquired with age (such as cancer) are frequently accompanied by dramatic changes in the genome structure. The striking recurrence of the characteristic pattern of genome changes for each disease type underlines that they are strongly linked to the disease development. However, what is not clear is to what degree these aberrations are causal for the disease and/or represent its consequences. With the recent advent of genome-wide methods for genome profiling, answers for those question fall within reach of modern Genomics. Further, effects of existing structural changes on disease predisposition, accumulation of genome changes with age and their somatic mosaicism require thorough investigation. These studies will help us to better understand disease progression, enhance our diagnostic methods and improve treatment strategies. The team will combine recent technological advances, such as high-throughput sequencing and bioinformatics expertise to investigate dynamics of genome changes in populations and individual organisms. Exploration of genome alterations in model organisms and comparisons with data from human genomes will advance our understanding of formation, evolution and consequences of age-related changes in our genomes.
    • Sin O, de Jong T, Kudron M , Zaini A , Aprile FA , Seinstra R, Mata-Cabana A, Stroo E, Willinge Prins R, Martineau C, Wang HH, Hogewerf W, Steinhof A, Wanker EE, Vendruscolo M, Calkhoven CF, Reinke V, Guryev V, Nollen EAA. (2017) Identification of an RNA Pol III-associated regulator of small non-coding RNAs that is linked with disease-associated protein agregation. Molecular Cell.
    • Hehir-Kwa JY, Marschall T, Kloosterman WP, Francioli LC, Baaijens JA, Dijkstra LJ, Abdellaoui A, Koval V, Thung DT, Wardenaar R, Renkens I, Coe BP, Deelen P, de Ligt J, Lameijer EW, van Dijk F, Hormozdiari F, The Genome of the Netherlands Consortium, Uitterlinden AG, van Duijn CM, Eichler EE, de Bakker PIW, Swertz MA, Wijmenga C, van Ommen GB, Slagboom PE, Boomsma DI, Schönhuth A, Ye K, Guryev V. (2016) A high-quality human reference panel reveals the complexity and distribution of genomic structural variants. Nature Communications.
    • Porubský D, Sanders AD, van Wietmarschen N, Falconer E, Hills M, Spierings DC, Bevova MR, Guryev V, Lansdorp PM. (2016) Direct chromosome-length haplotyping by single-cell sequencing. Genome Research.
    • Janssens GE, Meinema AC, González J, Wolters JC, Schmidt A, Guryev V, Bischoff R, Wit EC, Veenhoff LM, Heinemann M. (2015) Protein biogenesis machinery is a driver of replicative aging in yeast. eLife.
    • Chereji RV, Kan T-W, Grudniewska MK, Romashchenko AV, Berezikov E, Zhimulev IF, Guryev V, Morozov AV, & Moshkin YM. (2015) Genome-wide profiling of nucleosome sensitivity and chromatin accessibility in Drosophila melanogaster. Nucleic Acids Research.
    • Bischoff R, Permentier H, Guryev V, Horvatovich P. (2015) Genomic variability and protein species - Improving sequence coverage for proteogenomics. Journal of Proteomics.
    • van der Sligte NE, Scherpen FJG, Ter Elst A, Guryev V, van Leeuwen FN, de Bont ESJM. (2015) Effect of IKZF1 deletions on signal transduction pathways in Philadelphia chromosome negative pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Experimental Hematology & Oncology.
    • Francioli LC, Polak PP, Koren A, Menelaou A, Chun S, Renkens I, van Duijn CM, Swertz M, Wijmenga C, van Ommen G, Slagboom PE, Boomsma DI, Ye K, Guryev V, Arndt PF, Kloosterman WP, de Bakker PIW, Sunyaev SR. (2015)  Genome-wide patterns and properties of de novo mutations in humans. Nature Genetics.
    • Franke L, el Bannoudi H, Jansen DTSL, Kok K, Trynka G, Diogo D, Swertz M, Fransen K, Knevel R, Gutierrez-Achury J, Ärlestig L , Greenberg JD, Kremer J, Pappas DA, Kanterakis A, Weersma RK, van der Helm-van Mil AHM, Guryev V, Rantapää-Dahlqvist S, Gregersen PK, Plenge RM, Wijmenga C, Huizinga TWJ, Ioan-Facsinay A, Toes REM,  Zhernakova A. (2015) Association analysis of copy numbers of FC-gamma receptor genes for rheumatoid arthritis and other immune-mediated phenotypes. European Journal of Human Genetics.
    • van der Sligte NE, Kampen KR, ter Elst A, Scherpen FJG, Meeuwsen-de Boer TGJ, Guryev V, van Leeuwen FN, Kornblau SM, de Bont ESJM. (2015) Essential role for cyclic-AMP responsive element binding protein 1 (CREB) in the survival of acute lymphoblastic leukemia. Oncotarget.
    • Hermsen R, de Ligt J, Spee W, Blokzijl F, Schäfer S, Adami E, Boymans S, Flink S, van Boxtel R, van der Weide RH, Aitman T, Hübner N, Simonis M, Tabakoff B, Guryev V,  Cuppen E. (2015) Genomic landscape of rat strain and substrain variation. BMC Genomics.
    • Kloosterman WP, Francioli LC, Hormozdiari F, Marschall T, Hehir-Kwa JY, Abdellaoui A, Lameijer E-W, Moed MH, Koval V, Renkens I, van Roosmalen MJ, Arp P, Karssen LC, Coe BP, Handsaker RE, Suchiman ED, Cuppen E, Thung DT, McVey M, Wendl MC, Uitterlinden A, van Duijn CM, Swertz MA, Wijmenga C, van Ommen GB, Slagboom PE, Boomsma DI, Schönhuth A, Eichler  EE, de Bakker PIW, Ye K, Guryev V. (2015)  Characteristics of de novo structural changes in the human genome. Genome Research.
    • Samanas NB, Commers TW, Dennison KL, Harenda QE, Kurz SG, Lachel CM, Wavrin KL, Bowler M, Nijman IJ, Guryev V, Cuppen E, Hubner N, Sullivan R, Vezina CM, Shull JD. (2015) Genetic Etiology of Renal Agenesis: Fine Mapping of Renag1 and Identification of Kit as the Candidate Functional Gene. Plos One.
    • van der Sligte NE, Scherpen FJG, Meeuwsen-de Boer TGJ, Lourens HJ, Ter Elst A, Diks SH, Guryev V, Peppelenbosch MP, van Leeuwen FN, de Bont ESJM. (2015) Kinase activity profiling reveals active signal transduction pathways in pediatric acute lymphoblastic leukemia: A new approach for target discovery. Proteomics.
    • Junker JP, Noël ES, Guryev V, Peterson KA, Shah G, Huisken J, McMahon AP, Berezikov E, Bakkers J, van Oudenaarden, A. (2014) Genome-wide RNA Tomography in the Zebrafish Embryo. Cell.
    • Sampson AK, Mohammed D, Beattie W, Graham D, Kenyon CJ, Al-Dujaili EAS, Guryev V, Mcbride MW,  Dominiczak AF. (2014) Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat. Journal of Hypertension.
    • Baud A, Guryev V, Hummel O, Johannesson M, Flint J. (2014) Genomes and phenomes of a population of outbred rats and its progenitors. Scientific Data.
    • Kampen KR, Ter Elst A, Mahmud, H, Scherpen FJG, Diks SH, Peppelenbosch MP, de Haas V, Guryev V, de Bont ESJM. (2013) Insights in dynamic kinome reprogramming as a consequence of MEK inhibition in MLL-rearranged AML. Leukemia.
    • Low TY, van Heesch S, van den Toorn H, Giansanti P, Cristobal A, Toonen P, Schafer S, Hübner N, van Breukelen B, Mohammed S, Cuppen E, Heck AJ, Guryev V. (2013) Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics analysis. Cell Reports.
    • Ye K, Beekman M, Lameijer E-W, Zhang Y, Moed MH, van den Akker EB, Deelen J, Houwing-Duistermaat JJ, Kremer D, Anvar SY, Laros JFJ, Jones D, Raine K, Blackburne B, Potluri S, Long Q, Guryev V, van der Breggen R, Westendorp RGJ, ’t Hoen PAC, den Dunnen J, van Ommen GJB, Willemsen G, Pitts SJ, Cox DR, Ning Z, Boomsma DI, Slagboom PE. (2013) Aging as accelerated accumulation of somatic variants: whole-genome sequencing of centenarian and middle-aged monozygotic twin pairs. Twin Research and Human Genetics : The Official Journal of the International Society for Twin Studies.
    • Atanur SS, Diaz AG, Maratou K, Sarkis A, Rotival M, Game L, Tschannen MR, Kaisaki PJ, Otto GW, Ma MCJ, Keane TM, Hummel O, Saar K, Chen W, Guryev V, Gopalakrishnan K, Garrett MR, Joe B, Citterio L, Bianchi G, McBride  M, Dominiczak A, Adams DJ, Serikawa T, Flicek P, Cuppen E, Hubner N, Petretto E, Gauguier D, Kwitek A, Jacob H, Aitman TJ. (2013) Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. Cell.
    • Boomsma DI, Wijmenga C, Slagboom EP, Swertz MA, Karssen LC, Abdellaoui  A, Ye K, Guryev V, Vermaat M, van Dijk F, Francioli LC, Hottenga, JJ, Laros JFJ, Li Q, Li Y, Cao H, Chen R, Du Y, Li N, Cao S, van Setten J, Menelaou A, Pulit SL, Hehir-Kwa JY, Beekman M, Elbers CC, Byelas H, de Craen AJM, Deelen P, Dijkstra M, den Dunnen JT, de Knijff P, Houwing-Duistermaat J, Koval V, Estrada K, Hofman A, Kanterakis A, Enckevort D, van Duijn CM. (2013) The Genome of the Netherlands: design, and project goals. European Journal of Human Genetics.
    • Rat Genome Sequencing and Mapping Consortium. (2013) Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nature Genetics.
    • van Heesch S, Mokry M, Boskova V, Junker W, Mehon R, Toonen P, de Bruijn E, Shull JD, Aitman TJ, Cuppen E, Guryev V. (2013) Systematic biases in DNA copy number originate from isolation procedures. Genome Biology.
    • van Heesch S, Kloosterman WP, Lansu N, Ruzius FP, Levandowsky E, Lee CC, Zhou S, Goldstein S, Schwartz DC, Harkins TT, Guryev V, Cuppen E. (2013) Improving mammalian genome scaffolding using large insert mate-pair next-generation sequencing. BMC Genomics.
    • Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbergen E, Renkens I, Duran K, Ballarati L, Vergult S, Giardino D, Hansson K, Ruivenkamp CAL, Jager M, van Haeringen A, Ippel EF, Haaf T, Passarge E, Hochstenbach R, Menten B, Larizza L, Guryev V, Poot M,and Cuppen E (2012) Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell reports.
    • Clark MD, Guryev V, Bruijn Ed, Nijman IJ, Tada M, Wilson C, Deloukas P, Postlethwait JH, Cuppen E, Stemple DL. (2011) Single nucleotide polymorphism (SNP) panels for rapid positional cloning in zebrafish. Methods in Cell Biology.
    • Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijn E, Bakker SC, Letteboer T, van Nesselrooij B, Hochstenbach R, Poot M, Cuppen E. (2011) Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Human molecular genetics.
    • Atanur SS, Birol I, et al.. (2010) The genome sequence of the spontaneously hypertensive rat: Analysis and functional significance. Genome research.
    • Mokry M, Feitsma H, Nijman IJ, de Bruijn E, van der Zaag PJ, Guryev V, Cuppen E. (2010) Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing libraries. Nucleic Acids Research.
    • Pontier DB, Kruisselbrink E, Guryev V, Tijsterman M.. (2009) Isolation of deletion alleles by G4 DNA-induced mutagenesis. Nature Methods.
    • Guryev V, Cuppen E. (2009) Next-generation sequencing approaches in genetic rodent model systems to study functional effects of human genetic variation. FEBS letters.
    • Kruisselbrink E, Guryev V, Brouwer K, Pontier DB, Cuppen E, Tijsterman M. (2008) Mutagenic capacity of endogenous G4 DNA underlies genome instability in FANCJ-defective C. elegans. Current Biology.
    • Guryev V, Saar K, Adamovic T, Verheul M, van Heesch SA, Cook S, Pravenec M, Aitman T, Jacob H, Shull JD, Hubner N, Cuppen E. (2008) Distribution and functional impact of DNA copy number variation in the rat. Nature genetics.
    • STAR Consortium. (2008) SNP and haplotype mapping for genetic analysis in the rat. Nature genetics.
    • Cuppen E, Gort E, Hazendonk E, Mudde J, van de Belt J, Nijman IJ, Guryev V, Plasterk RH. (2007) Efficient target-selected mutagenesis in Caenorhabditis elegans: toward a knockout for every gene. Genome Research.
    • Berezikov E, Guryev V, Cuppen E. (2007) Exploring conservation of transcription factor binding sites with CONREAL. Methods in Molecular Biology.
    • Guryev V, Smits BM, van de Belt J, Verheul M, Hubner N, Cuppen E. (2006) Haplotype block structure is conserved across mammals. PLoS Genetics.
    • Guryev V, Koudijs MJ, Berezikov E, Johnson SL, Plasterk RH, van Eeden FJ, Cuppen E. (2006) Genetic variation in the zebrafish. Genome research.
    • Berezikov E, Guryev V, Cuppen E. (2005) CONREAL web server: identification and visualization of conserved transcription factor binding sites. Nucleic Acids Research.
    • Smits BM, Peters TA, Mul JD, Croes HJ, Fransen JA, Beynon AJ, Guryev V, Plasterk RH, Cuppen E. (2005) Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics. Genetics.
    • Guryev V, Berezikov E, Cuppen E. (2005) CASCAD: a database of annotated candidate single nucleotide polymorphisms associated with expressed sequences. BMC Genomics.
    • Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E. (2005) Phylogenetic shadowing and computational identification of human microRNA genes. Cell.
    • Guryev V, Berezikov E, Malik R, Plasterk RH, Cuppen E. (2004) Single nucleotide polymorphisms associated with rat expressed sequences. Genome research.
    • Berezikov E, Guryev V, Plasterk RH, Cuppen E. (2003) CONREAL: conserved regulatory elements anchored alignment algorithm for identification of transcription factor binding sites by phylogenetic footprinting. Genome research.
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