Genetic Instability and Ageing

We have developed novel techniques including single cell DNA (strand) sequencing techniques that allow accurate identification of numerical chromosomal abnormalities and specific sister chromatids in individual cells. For studies of telomere attrition and numerical chromosomal abnormalities in aging specific cells are analysed by flow cytometry and sorted as single cells. Such cells include cells from participants in the LifeLines project in Groningen (160,000 individuals). Studies of human cells are complemented using cells from patients and studies in suitable mouse models. We are specifically interested to measure telomere dysfunction and aneuploidy in stem cells and more differentiated cell types, to identify genetic and other factors regulating human leukocyte telomere length and to study the role of genetic instability and chromosomal abnormalities in cells in relation to normal human ageing and specific diseases.

• Kazemier HG, Paeschke K, Lansdorp PM. (2017) Guanine quadruplex monoclonal antibody 1H6 cross-reacts with restrained thymidine-rich single stranded DNA. Nucleic Acids Research.
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• 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.    
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• Sanders AD, Hills M, Porubský D, Guryev V, Falconer E, Lansdorp PM. (2016) Characterizing polymorphic inversions in human genomes by single-cell sequencing. Genome Research.  
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• van den Bos H, Spierings DC, Taudt AS, Bakker B, Porubský D, Falconer E, Novoa C, Halsema N, Kazemier HG, Hoekstra-Wakker K, Guryev V, den Dunnen WF, Foijer F, Tatché MC, Boddeke HW, Lansdorp PM. (2016) Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons. Genome Biology.
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• Lansdorp PM. (2016) Telomeres on Steroids — Turning Back the Mitotic Clock? New England Journal of Medicine.
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• van Wietmarschen N, Lansdorp PM. (2016) Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells. Nucleic Acids Research.
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• Hoffmann RF, Moshkin YM, Mouton S, Grzeschik NA, Kalicharan RD, Kuipers J, Wolters AH, Nishida K, Romashchenko AV, Postberg J, Lipps H, Berezikov E, Sibon OC, Giepmans BN, Lansdorp PM. (2015) Guanine quadruplex structures localize to heterochromatin. Nucleic Acids Research.
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• Bakker B, van der Bos H, Lansdorp PM, Foijer F. (2015) How to count chromosomes in a cell: An overview of current and novel technologies. Bioessays.
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• Buganim Y, Markoulaki S, van Wietmarschen N, Hoke H, Wu T, Ganz K, Akhtar-Zaidi B, He Y, Abraham BJ, Porubsky D, Kulenkampff E, Faddah DA, Shi L, Gao Q, Sarkar S, Cohen M, Goldmann J, Nery JR, Schultz MD, Ecker JR, Xiao A, Young RA, Lansdorp PM, Jaenisc. (2014) The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection. Cell Stem Cell.
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• Lisaingo K, Uringa EJ, Lansdorp PM. (2014) Resolution of telomere associations by TRF1 cleavage in mouse embryonic stem cells. Molecular Biology of the Cell.
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• Henderson A, Wu Y, Huang YC, Chavez EA, Platt J, Johnson FB, Brosh RM Jr, Sen D, Lansdorp PM. (2014) Detection of G-quadruplex DNA in mammalian cells. Nucleic Acids Research.
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• Hills M, O'Neill K, Falconer E, Brinkman R, Lansdorp PM. (2013) BAIT: Organizing genomes and mapping rearrangements in single cells. Genome Medicine.
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• Falconer E, Lansdorp PM. (2013) Strand-seq: a unifying tool for studies of chromosome segregation. Seminars in Cell and Developmental Biology.
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• van Wietmarschen N, Moradian A, Morin GB, Lansdorp PM, Uringa EJ. (2012) The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron-sulfur cluster protein assembly. Journal of Biological Chemistry.
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• Falconer E, Hills M, Naumann U, Poon SS, Chavez EA, Sanders AD, Zhao Y, Hirst M,Lansdorp PM. (2012) DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution. Nature Methods.
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• Aubert G, Baerlocher GM, Vulto I, Poon SS, Lansdorp PM. (2012) Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes. PLoS Genetics.
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• Uringa EJ, Lisaingo K, Pickett HA, Brind'Amour J, Rohde JH, Zelensky A, Essers J,Lansdorp PM. (2012) RTEL1 contributes to DNA replication and repair and telomere maintenance. Molecular Biology of the Cell.
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• Brind'Amour J, Lansdorp PM. (2011) Analysis of repetitive DNA in chromosomes by flow cytometry. Nature Methods.
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• Falconer E, Chavez E, Henderson A, Lansdorp PM. (2010) Chromosome orientation fluorescence in situ hybridization to study sister chromatid segregation in vivo. Nature protocols.
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• Falconer E, Chavez EA, Henderson A, Poon SS, McKinney S, Brown L, Huntsman DG,Lansdorp PM. (2010) Identification of sister chromatids by DNA template strand sequences. Nature.
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• Hills M, Lücke K, Chavez EA, Eaves CJ, Lansdorp PM. (2009) Probing the mitotic history and developmental stage of hematopoietic cells using single telomere length analysis (STELA). Blood.
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• Aubert G, Lansdorp PM. (2008) Telomeres and aging. Physiological Reviews.
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• Lansdorp PM. (2007) Immortal strands? Give me a break. Cell.
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• Baerlocher GM, Vulto I, de Jong G, Lansdorp PM. (2006) Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nature Protocols.
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• Ding H, Schertzer M, Wu X, Gertsenstein M, Selig S, Kammori M, Pourvali R, Poon S, Vulto I, Chavez E, Tam PP, Nagy A, Lansdorp PM. (2004) Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein. Cell.
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• Cheung I, Schertzer M, Rose A, Lansdorp PM. (2002) Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA. Nature Genetics.
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• Rufer N, Migliaccio M, Antonchuk J, Humphries RK, Roosnek E, Lansdorp PM. (2001) Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Blood.
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• Blasco MA1, Lee HW, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell.
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• Lansdorp PM, Verwoerd NP, van de Rijke FM, Dragowska V, Little MT, Dirks RW, Raap AK, Tanke HJ. (1996) Heterogeneity in telomere length of human chromosomes. Hum Mol Genet.
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• Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB, Lansdorp PM. (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A.
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