aneuploidy

Summary

Summary: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).

Top Publications

  1. ncbi The spindle-assembly checkpoint in space and time
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 8:379-93. 2007
  2. pmc Mutational inactivation of STAG2 causes aneuploidy in human cancer
    David A Solomon
    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
    Science 333:1039-43. 2011
  3. pmc Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres
    Silvia Remeseiro
    Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    EMBO J 31:2076-89. 2012
  4. ncbi To err (meiotically) is human: the genesis of human aneuploidy
    T Hassold
    Department of Genetics, Case Western Reserve University, 10, 900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Nat Rev Genet 2:280-91. 2001
  5. doi Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing
    Diana W Bianchi
    Mother Infant Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA
    Obstet Gynecol 119:890-901. 2012
  6. ncbi A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers
    Scott L Carter
    Children s Hospital Informatics Program at the Harvard MIT Division of Health Sciences and Technology Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 38:1043-8. 2006
  7. pmc Human aneuploidy: mechanisms and new insights into an age-old problem
    So I Nagaoka
    School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA
    Nat Rev Genet 13:493-504. 2012
  8. doi Causes and consequences of aneuploidy in cancer
    David J Gordon
    Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nat Rev Genet 13:189-203. 2012
  9. pmc Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast
    Norman Pavelka
    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA
    Nature 468:321-5. 2010
  10. doi Mitotic chromosomal instability and cancer: mouse modelling of the human disease
    Juan Manuel Schvartzman
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Rev Cancer 10:102-15. 2010

Research Grants

  1. Chromosome Analysis of Single Cells
    Brynn Levy; Fiscal Year: 2007
  2. Genome-wide recombination as a risk factor for nondisjunction
    NATASHA D HOLLIS; Fiscal Year: 2010
  3. Chou Zen Giam; Fiscal Year: 2014
  4. Joseph Heitman; Fiscal Year: 2016
  5. Vincent W Yang; Fiscal Year: 2016
  6. MARCELLE IVONNE CEDARS; Fiscal Year: 2016
  7. JASON MARK BECKTA; Fiscal Year: 2014
  8. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
  9. NFAT Signaling and Down Syndrome
    Gerald R Crabtree; Fiscal Year: 2012
  10. Feto-maternal DNA/RNA Trafficking: Biology and Application
    Diana W Bianchi; Fiscal Year: 2013

Detail Information

Publications358 found, 100 shown here

  1. ncbi The spindle-assembly checkpoint in space and time
    Andrea Musacchio
    Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Nat Rev Mol Cell Biol 8:379-93. 2007
    ..The SAC prevents chromosome mis-segregation and aneuploidy, and its dysfunction is implicated in tumorigenesis...
  2. pmc Mutational inactivation of STAG2 causes aneuploidy in human cancer
    David A Solomon
    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA
    Science 333:1039-43. 2011
    Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors...
  3. pmc Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres
    Silvia Remeseiro
    Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    EMBO J 31:2076-89. 2012
    ..SA1-null mouse embryonic fibroblasts show decreased proliferation and increased aneuploidy as a result of chromosome segregation defects...
  4. ncbi To err (meiotically) is human: the genesis of human aneuploidy
    T Hassold
    Department of Genetics, Case Western Reserve University, 10, 900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Nat Rev Genet 2:280-91. 2001
    b>Aneuploidy (trisomy or monosomy) is the most commonly identified chromosome abnormality in humans, occurring in at least 5% of all clinically recognized pregnancies...
  5. doi Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing
    Diana W Bianchi
    Mother Infant Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA
    Obstet Gynecol 119:890-901. 2012
    To prospectively determine the diagnostic accuracy of massively parallel sequencing to detect whole chromosome fetal aneuploidy from maternal plasma.
  6. ncbi A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers
    Scott L Carter
    Children s Hospital Informatics Program at the Harvard MIT Division of Health Sciences and Technology Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 38:1043-8. 2006
    We developed a computational method to characterize aneuploidy in tumor samples based on coordinated aberrations in expression of genes localized to each chromosomal region...
  7. pmc Human aneuploidy: mechanisms and new insights into an age-old problem
    So I Nagaoka
    School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA
    Nat Rev Genet 13:493-504. 2012
    ..The errors that lead to aneuploidy almost always occur in the oocyte but, despite intensive investigation, the underlying molecular basis has ..
  8. doi Causes and consequences of aneuploidy in cancer
    David J Gordon
    Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nat Rev Genet 13:189-203. 2012
    ..the structural chromosome rearrangements have received substantial attention, the role of whole-chromosome aneuploidy in cancer is much less well-understood...
  9. pmc Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast
    Norman Pavelka
    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA
    Nature 468:321-5. 2010
    b>Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer and adaptive evolution in experimental organisms...
  10. doi Mitotic chromosomal instability and cancer: mouse modelling of the human disease
    Juan Manuel Schvartzman
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nat Rev Cancer 10:102-15. 2010
    ..How chromosome instability (CIN) arises in tumours and what consequences it has are still, however, hotly debated issues. Here we review the recent literature with an emphasis on models that recapitulate observations from human disease...
  11. pmc Aneuploidy drives genomic instability in yeast
    Jason M Sheltzer
    David H Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute HHMI, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 333:1026-30. 2011
    b>Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity...
  12. ncbi Aneuploidy and cancer
    Harith Rajagopalan
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, Maryland 21231, USA
    Nature 432:338-41. 2004
    In contrast to normal cells, aneuploidy--alterations in the number of chromosomes--is consistently observed in virtually all cancers...
  13. pmc Aneuploidy and isochromosome formation in drug-resistant Candida albicans
    Anna Selmecki
    Department of Genetics, Cell Biology, and Development, University of Minnesota, 6 160 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA
    Science 313:367-70. 2006
    ..We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of ..
  14. pmc Meiotic origins of maternal age-related aneuploidy
    Teresa Chiang
    Department of Biology, University of Pennsylvania, Philadelphia, USA
    Biol Reprod 86:1-7. 2012
    Chromosome segregation errors in female meiosis lead to aneuploidy in the resulting egg and embryo, making them one of the leading genetic causes of spontaneous abortions and developmental disabilities in humans...
  15. doi Novel insights into genome plasticity in Eukaryotes: mosaic aneuploidy in Leishmania
    Yvon Sterkers
    Universite Montpellier 1, UFR Medecine, Laboratoire de Parasitologie Mycologie, Montpellier, France
    Mol Microbiol 86:15-23. 2012
    ..b>Aneuploidy has been suspected by several authors and it is now confirmed using state-of-the-art technologies such as high-..
  16. pmc Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans
    Min Ni
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS Biol 11:e1001653. 2013
    b>Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome...
  17. ncbi Tetraploidy, aneuploidy and cancer
    Neil J Ganem
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Curr Opin Genet Dev 17:157-62. 2007
    b>Aneuploidy is one of the most obvious differences between normal and cancer cells. However, there remains debate over how aneuploid cells arise and whether or not they are a cause or consequence of tumorigenesis...
  18. pmc Mechanisms of chromosomal instability
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Curr Biol 20:R285-95. 2010
    ..Understanding these mechanisms provides insight into the cellular consequences of CIN and reveals the possibility of exploiting CIN in cancer therapy...
  19. pmc Chromosomal instability and aneuploidy in cancer: from yeast to man
    Sarah J Pfau
    David H Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, 500 Main Street, Cambridge, Massachusetts 02139, USA
    EMBO Rep 13:515-27. 2012
    b>Aneuploidy is frequently associated with disease and developmental abnormalities. It is also a key characteristic of cancer...
  20. pmc Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation
    Robin M Ricke
    Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Cell Biol 193:1049-64. 2011
    ..Our results establish that Bub1 has oncogenic properties and suggest that Aurora B is a critical target through which overexpressed Bub1 drives aneuploidization and tumorigenesis...
  21. pmc Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy
    Guangbo Chen
    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA
    Nature 482:246-50. 2012
    b>Aneuploidy--the state of having uneven numbers of chromosomes--is a hallmark of cancer and a feature identified in yeast from diverse habitats...
  22. pmc Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood
    H Christina Fan
    Department of Bioengineering, Stanford University and Howard Hughes Medical Institute, 318 Campus Drive, Clark Center, Room E300, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 105:16266-71. 2008
    ..approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of ..
  23. pmc Identification of aneuploidy-selective antiproliferation compounds
    Yun Chi Tang
    David H Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA
    Cell 144:499-512. 2011
    b>Aneuploidy, an incorrect chromosome number, is a hallmark of cancer. Compounds that cause lethality in aneuploid, but not euploid, cells could therefore provide new cancer therapies...
  24. pmc Identification of aneuploidy-tolerating mutations
    Eduardo M Torres
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 143:71-83. 2010
    b>Aneuploidy causes a proliferative disadvantage in all normal cells analyzed to date, yet this condition is associated with a disease characterized by unabated proliferative potential, cancer...
  25. doi Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation
    Karin Tarte
    INSERM U917, Universite Rennes 1, Rennes, France
    Blood 115:1549-53. 2010
    ..Moreover, some transient and donor-dependent recurring aneuploidy was detected in vitro, independently of the culture process...
  26. pmc Frequent aneuploidy among normal human hepatocytes
    Andrew W Duncan
    Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, Oregon, USA
    Gastroenterology 142:25-8. 2012
    ..Although polyploidization occurs in some types of human cells, the degree of aneuploidy in human hepatocytes is not known...
  27. pmc Mitochondrial hyperfusion induced by loss of the fission protein Drp1 causes ATM-dependent G2/M arrest and aneuploidy through DNA replication stress
    Wei Qian
    Department of Pharmacology and Chemical Biology, Hillman Cancer Center Pittsburgh, PA 15213 USA
    J Cell Sci 125:5745-57. 2012
    ..inhibition of mitochondrial fission protein Drp1 causes an unexpected delay in G2/M cell cycle progression and aneuploidy. In investigating the underlying molecular mechanism, we revealed that inhibiting Drp1 triggers replication ..
  28. pmc Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan
    Darren J Baker
    Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905, USA
    Nat Cell Biol 15:96-102. 2013
    ..Germline mutations that reduce BubR1 abundance cause aneuploidy, shorten lifespan and induce premature ageing phenotypes and cancer in both humans and mice...
  29. ncbi Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells
    Jonathan S Draper
    Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK
    Nat Biotechnol 22:53-4. 2004
    ..These observations are instructive for the future application of hES cells in transplantation therapies in which the use of aneuploid cells could be detrimental...
  30. pmc Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol
    D S Johnson
    Gene Security Network, Inc, 2686 Middlefield Road, Suite C, Redwood City, CA 94063, USA
    Hum Reprod 25:1066-75. 2010
    Preimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods to determine the karyotype of an embryo are expanding the scope of PGS.
  31. pmc Centrosome amplification drives chromosomal instability in breast tumor development
    Wilma L Lingle
    Division of Experimental Pathology, Tumor Biology Program, Mayo Clinic, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 99:1978-83. 2002
    ..In this study, we investigated the relationship of centrosome amplification with aneuploidy, chromosomal instability, p53 mutation, and loss of differentiation in human breast tumors...
  32. pmc Acquisition of aneuploidy provides increased fitness during the evolution of antifungal drug resistance
    Anna M Selmecki
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA
    PLoS Genet 5:e1000705. 2009
    ..Resistance to fluconazole, the most widely used antifungal, is often associated with acquired aneuploidy. Here we provide a longitudinal study of the prevalence and dynamics of gross chromosomal rearrangements, ..
  33. pmc Aneuploidy causes proteotoxic stress in yeast
    Ana B Oromendia
    Koch Institute for Integrative Cancer Research, Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02138, USA
    Genes Dev 26:2696-708. 2012
    Gains or losses of entire chromosomes lead to aneuploidy, a condition tolerated poorly in all eukaryotes analyzed to date. How aneuploidy affects organismal and cellular physiology is poorly understood...
  34. pmc Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing
    Sijia Lu
    Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
    Science 338:1627-30. 2012
    ..Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.
  35. pmc Expression in aneuploid Drosophila S2 cells
    Yu Zhang
    Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Biol 8:e1000320. 2010
    ..Our data indicate that expression dosage compensation dampens the effect of altered DNA copy number genome-wide. For the X chromosome, compensation includes fixed and dose-dependent components...
  36. pmc Proliferation of aneuploid human cells is limited by a p53-dependent mechanism
    Sarah L Thompson
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    J Cell Biol 188:369-81. 2010
    Most solid tumors are aneuploid, and it has been proposed that aneuploidy is the consequence of an elevated rate of chromosome missegregation in a process called chromosomal instability (CIN)...
  37. pmc An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes
    Aideen O'Doherty
    Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Science 309:2033-7. 2005
    ..Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies...
  38. pmc Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha
    Meelad M Dawlaty
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cell 133:103-15. 2008
    ..Here we show that animals with low amounts of RanBP2 develop severe aneuploidy in the absence of overt transport defects...
  39. pmc The ploidy conveyor of mature hepatocytes as a source of genetic variation
    Andrew W Duncan
    Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    Nature 467:707-10. 2010
    ..Our findings support a dynamic model of hepatocyte polyploidization, ploidy reversal and aneuploidy, a phenomenon that we term the 'ploidy conveyor'...
  40. doi Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos
    Cristina Gutiérrez-Mateo
    Reprogenetics, Livingston, New Jersey, USA
    Fertil Steril 95:953-8. 2011
    ..To validate and determine the best array-comparative genomic hybridization (aCGH; array-CGH) protocols for preimplantation genetic screening (PGS)...
  41. ncbi From polyploidy to aneuploidy, genome instability and cancer
    Zuzana Storchova
    Department of Pediatric Oncology of The Dana Farber Cancer Institute, Children s Hospital and Harvard Medical School, Room M621A, 44 Binney Street Boston, Massachusetts 02115, USA
    Nat Rev Mol Cell Biol 5:45-54. 2004
    ..Genetic instability in these cells might provide a route to aneuploidy and thereby contribute to the development of cancer.
  42. pmc Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma
    Rossa W K Chiu
    Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
    Proc Natl Acad Sci U S A 105:20458-63. 2008
    Chromosomal aneuploidy is the major reason why couples opt for prenatal diagnosis...
  43. pmc Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy
    Saskia J E Suijkerbuijk
    Department of Physiological Chemistry and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, The Netherlands
    Cancer Res 70:4891-900. 2010
    ..in the mitotic regulatory kinase BUBR1 are associated with the cancer-susceptible disorder mosaic variegated aneuploidy (MVA). In patients with biallelic mutations, a missense mutation pairs with a truncating mutation...
  44. pmc Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells
    Bret R Williams
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology MIT, Cambridge, MA 02139, USA
    Science 322:703-9. 2008
    b>Aneuploidy, an incorrect number of chromosomes, is the leading cause of miscarriages and mental retardation in humans and is a hallmark of cancer...
  45. ncbi The spindle checkpoint, aneuploidy, and cancer
    Rajnish Bharadwaj
    Department of Pharmacology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9041, USA
    Oncogene 23:2016-27. 2004
    Cancer cells contain abnormal number of chromosomes (aneuploidy), which is a prevalent form of genetic instability in human cancers...
  46. ncbi Marine toxin okadaic acid induces aneuploidy in CHO-K1 cells in presence of rat liver postmitochondrial fraction, revealed by cytokinesis-block micronucleus assay coupled to FISH
    Ludovic Le Hegarat
    AFSSA, Laboratoire d Etudes et de Recherches sur les Médicaments Vétérinaires et les Désinfectants, Unité de Toxicologie Alimentaire, B P 90203, 35302 Fougeres Cedex, France
    Environ Toxicol 19:123-8. 2004
    ..The uptake of OA into CHO-K1 cells and the biotransformation of the toxin are discussed...
  47. pmc QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data
    Stefano Colella
    Genomics Laboratory, Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nucleic Acids Res 35:2013-25. 2007
    ..probabilistic quantification of state classifications and significantly improves the accuracy of segmental aneuploidy identification and mapping, relative to existing analytical tools (Beadstudio, Illumina), as demonstrated by ..
  48. doi Transcriptomic profiling of human oocytes: association of meiotic aneuploidy and altered oocyte gene expression
    E Fragouli
    Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK
    Mol Hum Reprod 16:570-82. 2010
    ..One of the most important defects affecting oocytes is aneuploidy. Aneuploidy is also closely related with advancing maternal age, a phenomenon not well understood...
  49. pmc Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes
    Teresa Chiang
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104 6018, USA
    Curr Biol 20:1522-8. 2010
    b>Aneuploidy arising early in development is the leading genetic cause of birth defects and developmental disabilities in humans...
  50. doi Aneuploidy in the human blastocyst
    E Fragouli
    University of Oxford, Nuffield Department of Obstetrics and Gynaecology, Institute of Reproductive Sciences, Oxford, UK
    Cytogenet Genome Res 133:149-59. 2011
    ..g., IVF). While much is known concerning the incidence of aneuploidy during the first 3 days following fertilization, it is only in the last couple of years that large numbers of ..
  51. pmc Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma
    Samuel F Bakhoum
    Department of Biochemistry The Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA
    Clin Cancer Res 17:7704-11. 2011
    ..chromosome mis-segregation events as well as the inability to distinguish the role of CIN, which consists of increased rates of chromosome mis-segregation, from that of aneuploidy, which is a state of nondiploid chromosome number.
  52. pmc Karyotypic determinants of chromosome instability in aneuploid budding yeast
    Jin Zhu
    Stowers Institute for Medical Research, Kansas City, Missouri, United States of America
    PLoS Genet 8:e1002719. 2012
    Recent studies in cancer cells and budding yeast demonstrated that aneuploidy, the state of having abnormal chromosome numbers, correlates with elevated chromosome instability (CIN), i.e...
  53. pmc Transcriptional consequences of aneuploidy
    Jason M Sheltzer
    David H Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 109:12644-9. 2012
    b>Aneuploidy, or an aberrant karyotype, results in developmental disabilities and has been implicated in tumorigenesis...
  54. pmc New insights into the troubles of aneuploidy
    Jake J Siegel
    David H Koch Institute for Integrative Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Annu Rev Cell Dev Biol 28:189-214. 2012
    ..Errors in mitotic or meiotic cell division lead to aneuploidy, which places a burden of additional or insufficient gene products from the missegregated chromosomes on the ..
  55. pmc Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells
    Silvia Stingele
    Group of Maintenance of Genome Stability, Max Planck Institute of Biochemistry, Martinsried, Germany
    Mol Syst Biol 8:608. 2012
    ..Furthermore, using the quantitative data we investigated the changes of cellular pathways in response to aneuploidy. This analysis revealed specific and uniform alterations in pathway regulation in cells with extra chromosomes...
  56. pmc USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis
    Ying Zhang
    Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Invest 122:4362-74. 2012
    Most human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy by restraining the activity of the anaphase-promoting complex (APC)...
  57. pmc Human mesenchymal stem cell-replicative senescence and oxidative stress are closely linked to aneuploidy
    J C Estrada
    Department of Cardiovascular Development and Repair, Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III CNIC, Melchor Fernandez Almagro 3, Madrid, Spain
    Cell Death Dis 4:e691. 2013
    ..culture the senescence-prone hMSC subpopulation has a lower proliferation potential and a higher incidence of aneuploidy than the non-senescent subpopulation...
  58. pmc Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy
    Suzanne E Peterson
    Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, United States of America
    PLoS ONE 6:e23018. 2011
    ..This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that ..
  59. ncbi Inactivation of hCDC4 can cause chromosomal instability
    Harith Rajagopalan
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Nature 428:77-81. 2004
    b>Aneuploidy, an abnormal chromosome number, has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive...
  60. ncbi Constitutional aneuploidy in the normal human brain
    Stevens K Rehen
    Helen L Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA
    J Neurosci 25:2176-80. 2005
    The mouse brain contains genetically distinct cells that differ with respect to chromosome number manifested as aneuploidy (Rehen et al., 2001); however, the relevance to humans is not known...
  61. pmc Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
    Andrew J Holland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, California 92093 0670, USA
    Nat Rev Mol Cell Biol 10:478-87. 2009
    ..Most cancer cells are aneuploid and frequently missegregate chromosomes during mitosis. Indeed, aneuploidy is a common characteristic of tumours, and, for over 100 years, it has been proposed to drive tumour progression...
  62. pmc Chromosomal variation in neurons of the developing and adult mammalian nervous system
    S K Rehen
    Department of Pharmacology, School of Medicine, University of California, San Diego, CA 92093-0636, USA
    Proc Natl Acad Sci U S A 98:13361-6. 2001
    ..Here we present direct evidence for genomic variability, manifested as chromosomal aneuploidy, among developing and mature neurons...
  63. ncbi Effects of aneuploidy on cellular physiology and cell division in haploid yeast
    Eduardo M Torres
    Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, E17 233, 40 Ames Street, Cambridge, MA 02139, USA
    Science 317:916-24. 2007
    b>Aneuploidy is a condition frequently found in tumor cells, but its effect on cellular physiology is not known. We have characterized one aspect of aneuploidy: the gain of extra chromosomes...
  64. doi Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays
    Nathan R Treff
    Reproductive Medicine Associates of New Jersey, Morristown, New Jersey 07960, USA
    Fertil Steril 94:2017-21. 2010
    To develop and validate a whole genome amplification and single nucleotide polymorphism (SNP) microarray protocol for accurate single cell 24 chromosome aneuploidy screening.
  65. pmc Origin of multidrug resistance in cells with and without multidrug resistance genes: chromosome reassortments catalyzed by aneuploidy
    P Duesberg
    Department of Molecular and Cell Biology, Stanley Hall, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 98:11283-8. 2001
    ..of drug metabolizing genes or (ii) chromosome reassortments, catalyzed by cancer- and cell line-specific aneuploidy, which generate, via new gene dosage combinations, a plethora of cancer phenotypes, including drug resistance...
  66. ncbi Methylation reprogramming and chromosomal aneuploidy in in vivo fertilized and cloned rabbit preimplantation embryos
    Wei Shi
    Department of Molecular Animal Breeding and Biotechnology, University of Munich, 85764 Oberschleissheim, Germany
    Biol Reprod 71:340-7. 2004
    ..in situ hybridization with chromosome-specific BACs demonstrated significantly increased chromosomal aneuploidy rates in cumulus cell nuclear transfer rabbit embryos and embryos derived from nuclear transfer of rabbit ..
  67. ncbi Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age
    Keith T Jones
    Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Framlington Place, Newcastle, NE2 4HH, UK
    Hum Reprod Update 14:143-58. 2008
    ..Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a ..
  68. pmc Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo
    Elena Diaz-Rodriguez
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 105:16719-24. 2008
    ..As previously observed with overexpression of the Mad2 gene, hyperactivation of the mitotic checkpoint leads to aneuploidy in vitro and is sufficient to generate tumors in vivo that harbor significant levels of aneuploidy...
  69. pmc Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor
    Giulia Rancati
    Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO 64110, USA
    Cell 135:879-93. 2008
    ..The evolved cytokinesis phenotypes correlated with specific changes in the transcriptome. Polyploidy and aneuploidy were common genetic alterations in the best evolved strains, and aneuploidy could account for gene expression ..
  70. pmc Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum
    Philippe Leprohon
    Centre de Recherche en Infectiologie et Division de Microbiologie, Universite Laval, Quebec, Canada
    Nucleic Acids Res 37:1387-99. 2009
    ..Selection of a partial revertant line correlated antimomy resistance levels and the copy number of aneuploid chromosomes, suggesting a putative link between aneuploidy and drug resistance in Leishmania.
  71. doi Induction of aneuploidy by single-walled carbon nanotubes
    L M Sargent
    Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
    Environ Mol Mutagen 50:708-17. 2009
    ..Our results are the first to report disruption of the mitotic spindle by SWCNT. The nanotube bundles are similar to the size of microtubules that form the mitotic spindle and may be incorporated into the mitotic spindle apparatus...
  72. pmc The TLX1 oncogene drives aneuploidy in T cell transformation
    Kim De Keersmaecker
    Institute for Cancer Genetics, Columbia University, New York, New York, USA
    Nat Med 16:1321-7. 2010
    ..These results identify a previously unrecognized mechanism contributing to chromosomal missegregation and aneuploidy active at the earliest stages of tumor development in the pathogenesis of cancer.
  73. pmc Sensitivity of noninvasive prenatal detection of fetal aneuploidy from maternal plasma using shotgun sequencing is limited only by counting statistics
    H Christina Fan
    Department of Bioengineering, Stanford University and Howard Hughes Medical Institute, Stanford, California, United States of America
    PLoS ONE 5:e10439. 2010
    We recently demonstrated noninvasive detection of fetal aneuploidy by shotgun sequencing cell-free DNA in maternal plasma using next-generation high throughput sequencer...
  74. ncbi Aneuploidy and DNA replication in the normal human brain and Alzheimer's disease
    Birgit Mosch
    Paul Flechsig Institute of Brain Research, Department of Neuroanatomy, University of Leipzig, D 04109 Leipzig, Germany
    J Neurosci 27:6859-67. 2007
    ..It was our objective to distinguish between these two mechanisms for aneuploidy and to provide evidence for a functional cell cycle in AD...
  75. pmc Digital PCR for the molecular detection of fetal chromosomal aneuploidy
    Y M Dennis Lo
    Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, School of Public Health, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong Special Administrative Region, People s Republic of China
    Proc Natl Acad Sci U S A 104:13116-21. 2007
    ..We applied the sequential probability ratio test to interpret the digital PCR data. Computer simulation and empirical validation confirmed the high accuracy of the disease classification algorithm...
  76. ncbi Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability
    A H Peters
    Research Institute of Molecular Pathology IMP, Vienna Biocenter, Dr Bohrgasse 7, A 1030, Vienna, Austria
    Cell 107:323-37. 2001
    ..These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development...
  77. ncbi Bisphenol a exposure causes meiotic aneuploidy in the female mouse
    Patricia A Hunt
    Department of Genetics, Case Western Reserve University, Cleveland, OH 44106 4955, USA
    Curr Biol 13:546-53. 2003
    ....
  78. pmc Impaired Bub1 function in vivo compromises tension-dependent checkpoint function leading to aneuploidy and tumorigenesis
    Mark Schliekelman
    Curriculum in Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
    Cancer Res 69:45-54. 2009
    ..MEFs) display defects in chromosome congression to the metaphase plate, severe chromosome missegregation, and aneuploidy accompanied by high levels of premature senescence...
  79. doi Array comparative genomic hybridisation on first polar bodies suggests that non-disjunction is not the predominant mechanism leading to aneuploidy in humans
    A S Gabriel
    School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
    J Med Genet 48:433-7. 2011
    b>Aneuploidy (the presence of extra or missing chromosomes) arises primarily through chromosome segregation errors in the oocyte at meiosis I but the details of mechanism by which such errors occur in humans are the subject of some debate...
  80. ncbi Inhibition of JNK2 disrupts anaphase and produces aneuploidy in mammalian cells
    Rebecca A MacCorkle
    Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 279:40112-21. 2004
    ..This evidence suggests that JNK2 functions in maintaining the genomic stability of mammalian cells by signaling that is independent of cyclin-dependent kinase 1/cyclin B1 down-regulation...
  81. doi Multiplex ligation-dependent probe amplification (MLPA) as a stand-alone test for rapid aneuploidy detection in amniotic fluid cells
    Angelique J A Kooper
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Prenat Diagn 28:1004-10. 2008
    ..e. 13, 18, 21, X and Y) in amniotic fluid cells in routine prenatal clinical practice...
  82. pmc Mouse embryonic fibroblasts null for the Krüppel-like factor 4 gene are genetically unstable
    E G Hagos
    Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
    Oncogene 28:1197-205. 2009
    ..demonstrate that MEFs null for the Klf4 alleles are genetically unstable, as evidenced by the presence of aneuploidy, chromosome aberration and centrosome amplification...
  83. pmc Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro
    Helen M Picton
    Division of Reproduction and Early Development, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, UK
    Mol Hum Reprod 16:557-69. 2010
    This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. One hundred and eighty-eight fresh and cryopreserved embryos from 59 patients (33.9 +/- 0...
  84. pmc Refining tumor-associated aneuploidy through 'genomic recoding' of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas
    Rachael Thomas
    Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA
    Leuk Lymphoma 52:1321-35. 2011
    ..We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no ..
  85. pmc Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation
    Alan H Handyside
    London Bridge Fertility, Gynaecology and Genetics Centre, London, UK
    Eur J Hum Genet 20:742-7. 2012
    Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the ..
  86. ncbi A candidate model for Angelman syndrome in the mouse
    B M Cattanach
    Mammalian Genetics Unit, Medical Research Council, Harwell, Didcot, Oxon OX11 ORD, UK
    Mamm Genome 8:472-8. 1997
    ..A mouse model of AS is, therefore, strongly indicated...
  87. ncbi Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis
    Farideh Z Bischoff
    Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA
    Hum Reprod Update 8:493-500. 2002
    ..for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate...
  88. ncbi Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells
    Amy H Yang
    Biomedical Sciences, School of Medicine, University of California, San Diego, California 92093, USA
    J Neurosci 23:10454-62. 2003
    ..To substantiate these findings and address how neural aneuploidy arises, we examined individual neural progenitor cells (NPCs) undergoing mitosis...
  89. ncbi Growth arrest and chromosome instability in aneuploid yeast
    Osami Niwa
    Kazusa DNA Research Institute, 2 6 7 Kazusa Kamatari, Kisarazu, Chiba 292 0818, Japan
    Yeast 23:937-50. 2006
    ..In the present study, we investigated fission yeast aneuploids, focusing on the process through which aneuploidy is resolved into stable euploidy...
  90. pmc Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana
    Bruno Huettel
    Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Vienna, Austria
    PLoS Genet 4:e1000226. 2008
    b>Aneuploidy refers to losses and/or gains of individual chromosomes from the normal chromosome set...
  91. pmc The ATM-p53 pathway suppresses aneuploidy-induced tumorigenesis
    Min Li
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 107:14188-93. 2010
    ..Defects in this checkpoint can lead to chromosome missegregation and aneuploidy. An increasing body of evidence suggests that aneuploidy can play a causal role in tumorigenesis...
  92. pmc Oocyte cohesin expression restricted to predictyate stages provides full fertility and prevents aneuploidy
    Ekaterina Revenkova
    Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029 6574, USA
    Curr Biol 20:1529-33. 2010
    ..Aging human oocytes suffer a steep increase in chromosome missegregation and aneuploidy, which may be caused by loss of SCC through slow deterioration of cohesin [1-3]...
  93. pmc Aneuploidy and tumorigenesis
    Xiao Fang
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, United States
    Semin Cell Dev Biol 22:595-601. 2011
    b>Aneuploidy is a prominent phenotype of cancer. It refers to deviations from the normal number of chromosomes in a cell, as a result of whole-chromosome loss or gain...
  94. pmc High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells
    JEWEL DANIEL
    Department of Pathology and Johns Hopkins Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 108:5384-9. 2011
    ..aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 ..
  95. pmc Allele-specific copy number analysis of tumor samples with aneuploidy and tumor heterogeneity
    Markus Rasmussen
    Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Akademiska sjukhuset, SE 751 85 Uppsala, Sweden
    Genome Biol 12:R108. 2011
    ..Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors.
  96. ncbi Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation
    H Zhou
    Division of Pathology and Laboratory Medicine, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Nat Genet 20:189-93. 1998
    ..and distribution of centrosomes have been implicated in chromosome segregation abnormalities, leading to aneuploidy seen in many cancer cell types...
  97. pmc Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
    Laura Lentini
    Department of Cellular and Developmental Biology A, Monroy, University of Palermo, Viale delle Scienze, Palermo, Italy
    BMC Cancer 7:212. 2007
    ..CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification...
  98. pmc Shugoshin prevents cohesin cleavage by PP2A(Cdc55)-dependent inhibition of separase
    Dean Clift
    The Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Genes Dev 23:766-80. 2009
    ..Loss of both securin and Cdc55 leads to premature sister chromatid separation, resulting in aneuploidy. We propose that Cdc55 is a separase inhibitor that acts downstream from Shugoshin under conditions where sister ..
  99. pmc Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling
    Tanja van Harn
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Genes Dev 24:1377-88. 2010
    ..As a result, mitotic cells show chromatid breaks and chromatid cohesion defects. These aberrations lead to aneuploidy in the descendent cell population...
  100. pmc Dosage compensation and the global re-balancing of aneuploid genomes
    Matthias Prestel
    Adolf Butenandt Institute and Centre for Integrated Protein Science CiPSM, Ludwig Maximilians University, Schillerstrasse 44, 80336 Munich, Germany
    Genome Biol 11:216. 2010
    ..The dosage-compensation systems that evolved along with monosomic sex chromosomes exemplify the intricacies of compensating for differences in gene copy number by transcriptional regulation...
  101. pmc Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS)
    Norbert Gleicher
    Center for Human Reproduction CHR New York, NY, USA
    Reprod Biol Endocrinol 8:140. 2010
    ..Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy.

Research Grants74

  1. Chromosome Analysis of Single Cells
    Brynn Levy; Fiscal Year: 2007
    ..Current research is aimed at using this tool for detection of total aneuploidy in single cells...
  2. Genome-wide recombination as a risk factor for nondisjunction
    NATASHA D HOLLIS; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Human chromosome nondisjunction leads to a high frequency of aneuploidy. Nondisjunction is a leading cause of miscarriage, birth defects and mental retardation...
  3. Chou Zen Giam; Fiscal Year: 2014
    ..They, however, develop dramatic nuclear abnormalities in the form of multinucleation and DNA aneuploidy. Importantly, down-regulation of p27 and mis-localization of p21 are common in Tax-expressing HTLV-1-transformed ..
  4. Joseph Heitman; Fiscal Year: 2016
    ..Aim 2 focuses on the de novo generation of genotypic and phenotypic plasticity by sexual reproduction involving aneuploidy and diploidy. Aim 3 addresses sexual reproduction and the basis of hypervirulence in the C...
  5. Vincent W Yang; Fiscal Year: 2016
    ..ablation of KLF4 results in genetic instability including centrosome amplification, chromosome aberrations and aneuploidy. Based on these findings, we hypothesize that KLF4 is a critical tumor suppressor of CRC and is involved in ..
  6. MARCELLE IVONNE CEDARS; Fiscal Year: 2016
    ..The decline in live birth rate reflects an increase in oocyte aneuploidy, leading to failure of implantation and increased risk for miscarriages and birth defects...
  7. JASON MARK BECKTA; Fiscal Year: 2014
    ..However, when cultured in vitro, PSCs commonly acquire genetic abnormalities (e.g., aneuploidy)...
  8. Roles of the mammalian CST complex in DNA replication and chromosome cohesion
    JASON AARON STEWART; Fiscal Year: 2013
    ..associated with cancer initiation, such as translocations, deletions, chromosome fusions, gene duplication and aneuploidy. Several genetic disorders, termed cohesionopathies, are also associated with SCC loss and chromosome breakage...
  9. NFAT Signaling and Down Syndrome
    Gerald R Crabtree; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The most common human aneuploidy is complete or partial trisomy of human chromosome 21 (HSA21), which results in Down Syndrome (DS)...
  10. Feto-maternal DNA/RNA Trafficking: Biology and Application
    Diana W Bianchi; Fiscal Year: 2013
    ..the proposed experimental plan will significantly expand the current scope of prenatal diagnosis beyond anatomy, aneuploidy, and single gene disorder detection...
  11. Wei Dai; Fiscal Year: 2016
    ..studies reveal that arsenic exposure induces the formation of micronuclei, chromosomal aberrations, and aneuploidy, which may be a culprit in the genesis of cancer since most solid tumors are aneuploid...
  12. Michael Freitag; Fiscal Year: 2015
    ..Defective centromeres result in faulty chromosome segregation and aneuploidy, implicated as one cause of cancer...
  13. Barbara J Meyer; Fiscal Year: 2016
    ..Our protein complexes give us insight into the mechanisms underlying the genome rearrangements associated with such a cancerous state. ..
  14. Molecular Basis of Nuchal Edema
    Young Kwon Hong; Fiscal Year: 2013
    ..to an abnormal fluid accumulation during human pregnancy and has been associated with fetuses having chromosomal aneuploidy. NE can be clinically diagnosed by ultrasound and the measurement of NE, also called nuchal translucency ..
  15. The Role of Cks Proteins in Mammalian Meiosis
    Charles H Spruck; Fiscal Year: 2010
    ..transition of Ml is particularly relevant clinically because its dysregulation is associated with oocyte aneuploidy in women and infertility in both men and women...
  16. Mechanics and regulation of chromosome dynamics in meiotic prophase
    MICHAEL EDWARD DRESSER; Fiscal Year: 2012
    ..frequently arises from the failure of meiosis to faithfully haploidize the genome, instead giving rise to aneuploidy. Typically, chromosome missegregations and rearrangements appear to stem from problems in the processes that ..
  17. Environmental Endocrine Disruptors and Human Sperm Chromosomal Abnormalities
    Melissa Perry; Fiscal Year: 2012
    ..segregation during meiosis result in structural aberrations and imbalances in chromosome number known as aneuploidy. Most new gene mutations seen in offspring and most abnormalities in the numbers of the sex chromosomes arise ..
  18. Environmental and genetic regulation of copy number variation (CNV)
    THOMAS PETES; Fiscal Year: 2010
    ..recombination between dispersed repeats, microhomology- mediated recombination, non-homologous end joining or aneuploidy), we will characterize the strains with CNV events using DNA microarrays and a gel system that separates intact ..
  19. Nihal Ahmad; Fiscal Year: 2016
    ..Plk1 dysregulation has been shown to result in chromosomal instability, aneuploidy and tumor development. However, the functional role of Plk1 in melanoma development is not well understood...
  20. Christine M Disteche; Fiscal Year: 2016
    ..The role of escape genes in sex-specific differences and in sex chromosome aneuploidy is poorly understood...
  21. Design of a high-throughput screen for chemicals that cause meiotic aneuploidy
    Patrick Allard; Fiscal Year: 2011
    ..of meiotic aneuploidies, the screening of environmental toxicants for their ability to disrupt meiosis and cause aneuploidy has been severely lagging...
  22. High Throughput Transcriptome Sequencing for Systematic Detection of Recurrent Tr
    Chandan Kumar; Fiscal Year: 2012
    ..As a test case, we propose to analyze pancreatic cancer, which is the 4th most common cause of cancer related deaths in the US, with the worst prognosis of all major malignancies (5 year survival <3%). ..
  23. Matthew J O'Connell; Fiscal Year: 2015
    ..We have previously shown that Smc5/6 mutants show high levels of aneuploidy, and show failed mitoses following DNA damage or Top2 dysfunction...
  24. Russ B Hauser; Fiscal Year: 2016
    ..BPA has been shown in experimental studies to lead to oocyte aneuploidy, pregnancy loss and adversely affect spermatogenesis...
  25. Needhi Bhalla; Fiscal Year: 2016
    ....
  26. John C Schimenti; Fiscal Year: 2016
    ..Errors in meiosis can lad to aneuploidy, chromosome aberrations, or gene mutations...
  27. JoAnne Engebrecht; Fiscal Year: 2016
    ..These studies have direct relevance to understanding the increased frequency of sex chromosome aneuploidy associated with human meiosis resulting in developmental disorders including Turner and Klinefelter's ..
  28. Meiotic spindle formation in Drosophila females
    Kim S McKim; Fiscal Year: 2010
    ..Defects in this process lead to aneuploidy in the fertilized egg and have serious consequences on development, often resulting in death of the developing ..
  29. Harmit S Malik; Fiscal Year: 2016
    ..DNA is required for correct chromosome segregation, defects in which can lead to infertility as well as to aneuploidy - commonly found in birth defects like trisomy (e.g. Down's syndrome) and in transitions to cancer...
  30. Comparative Analysis of DNA Break Repair in Short- and Long-Lived Rodent Species
    Vera Gorbunova; Fiscal Year: 2012
    ..We will examine aneuploidy rate by flow cytometry and analyze specific chromosomal aberrations by karyotyping...
  31. Organization and Regulation of Eukaryotic Centromeres
    BETH SULLIVAN; Fiscal Year: 2009
    ..Errors in chromosome inheritance lead to chromosome abnormalities (aneuploidy) that cause many birth defects, such as Down Syndrome and miscarriages, and are the hallmarks of almost all ..
  32. Kim S McKim; Fiscal Year: 2016
    ..Defects in this process lead to aneuploidy in the fertilized egg and usually in death of the developing embryo...
  33. Kinetochore Function and Cell Cycle Progression Revision
    Katsumi Kitagawa; Fiscal Year: 2012
    ..Having an abnormal number of chromosomes is called aneuploidy, and this situation can cause cancer to develop...
  34. Arsenic Induced Miotic Arrest Associated Apoptosis
    J Christopher States; Fiscal Year: 2009
    ..the carcinogenic form of arsenic found in drinking water, disrupts mitosis causing an anaphase delay and induces aneuploidy in normal diploid human fibroblasts and peripheral blood lymphocytes, and mitotic arrest associated apoptosis (..
  35. GENETIC AND MOLECULAR ANALYSIS OF YEAST DNA REPLICATION
    Robert A Sclafani; Fiscal Year: 2012
    ..Low fidelity replication and error-prone post-replication DNA repair can result in chromosomal aneuploidy and mutations, which can cause aging, cancer and birth defects...
  36. The role of the first mammalian N-term. methyltransferase, NRMT, in tumorigenesis
    Christine E Schaner-Tooley; Fiscal Year: 2012
    ..Reduction of NRMT also results in a multi-spindle phenotype, and the associated aneuploidy is often considered to contribute to cancer progression...
  37. Malathy P V Shekhar; Fiscal Year: 2015
    ..Rad6B is overexpressed in BrCa. Constitutive overexpression of Rad6B in normal breast cells induces aneuploidy and cisplatin (CDDP) resistance, whereas Rad6B suppression confers CDDP sensitivity...
  38. DAVID GERARD PETERS; Fiscal Year: 2015
    ..method that significantly improves the sensitivity and specificity of non-invasive prenatal detection of aneuploidy in the first trimester...
  39. KAREN MICHELE BERKOWITZ; Fiscal Year: 2016
    ..Errors in these processes can lead to chromosome mis-segregation and ultimately, aneuploidy in humans. Yet the molecular basis of the defects is not well understood...
  40. Richard M Schultz; Fiscal Year: 2016
    An increase in aneuploidy is a major cause for the marked decline in human female fertility commencing 35 years-of-age;the incidence of aneuploidy in eggs from women increases to 35% around 40 years-of-age, and is likely to be even ..
  41. Characterization of the Synapis Checkpoint in C. elegans Meiosis
    Needhi Bhalla; Fiscal Year: 2010
    ..Occasionally, an embryo inherits an extra chromosome that is not lethal but can cause cancer predisposition or serious developmental defects. ..
  42. Edward E Schmidt; Fiscal Year: 2015
    ..We predict that hepatic stresses, replication, ploidy, aneuploidy, and time will affect hepatocyte lineage life history dynamics...
  43. Kevin C Slep; Fiscal Year: 2014
    ..result in a wide spectrum of diseases including, but not limited to neurodegeneration, spastic paraplegia and aneuploidy. TOG domains are tubulin binding domains found in two conserved protein families that regulate microtubule ..
  44. ROCK II-mediated regulation of centrosome duplication / centrosome amplification
    Kenji Fukasawa; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Chromosome instability (and resulting aneuploidy) has been recognized as a hallmark of cancer cells, and contributes to tumor progression by facilitating the genetic alterations required for ..
  45. Regulation of Cytokinesis and Tumor Formation by RhoA
    ANN LOUISE MILLER; Fiscal Year: 2013
    ..K99 phase of this grant and continue in the independent R00 phase, examine the controversial question of whether aneuploidy, the condition of having more than or less than the normal number of chromosomes, is a cause or consequence of ..
  46. The Role of Fbxw7 in genetic instability and cancer
    Jian Hua Mao; Fiscal Year: 2012
    ..the functional relationship between Fbxw7 and Aurora-A kinase in control of chromosome segregation and aneuploidy, both in vitro and in vivo...
  47. Nucleoporins in Chromosomal Instability and Cancer
    Jan M van Deursen; Fiscal Year: 2012
    ABSTRACT The vast majority of human cancers have abnormal numbers of chromosomes, known as aneuploidy. However, the molecular basis of aneuploidy and its role in tumor development remain poorly understood...
  48. Molecular mechanisms underlying chromosomal instability and aneuploidy
    Wei Dai; Fiscal Year: 2012
    ..b>Aneuploidy, a common form of genomic instability, is a direct result of chromosomal missegregation during mitosis...
  49. MICHAEL ALTERMAN LAMPSON; Fiscal Year: 2016
    ..Defective regulation leads to unequal chromosome segregation and aneuploidy, which is strongly associated with human cancer in mitotic divisions and pregnancy loss and developmental ..
  50. Center for Reproductive Research at Northwestern University
    Teresa K Woodruff; Fiscal Year: 2012
    ..have abnormal meiotic spindles, including abnormal chromosome alignment and microtubular matrix composition and aneuploidy. Lonnie Shea and team (Project I) developed an in vitro follicle maturation system, an attractive model for ..
  51. Don W Cleveland; Fiscal Year: 2016
    ..of the transformation cascade in inherited cancers caused by heterozygous mutation in tumor suppressor genes and the more widespread aneuploidy characteristic of advance tumors thought to drive acquisition of malignant growth properties.
  52. Analysis of checkpoint function in the germ line.
    JoAnne Engebrecht; Fiscal Year: 2010
    ..Our studies are aimed at understanding how errors arise during this process. In humans, such errors result in infertility, pregnancy loss and birth defects such as Down Syndrome. ..
  53. KEVIN DANIEL CORBETT; Fiscal Year: 2016
    ..As such, aneuploidy is the leading genetic cause of miscarriage and of mental retardation (e.g...
  54. Molecular Mechanisms of Chromosome Segregation in Yeast
    Jennifer L Gerton; Fiscal Year: 2012
    ..When chromosomes are not accurately divided between cells, aneuploidy results, which is the state of having too many or too few chromosomes...
  55. Patrick Allard; Fiscal Year: 2015
    ..of meiotic aneuploidies, the screening of environmental toxicants for their ability to disrupt meiosis and cause aneuploidy has been severely lagging...
  56. Mechanistic Analysis Of Microtubule Based Motors
    Susan P Gilbert; Fiscal Year: 2012
    ..to new strategies for high throughput screens that select compounds to enhance cancer cell death rather than aneuploidy after chemotherapy...
  57. SUSAN BIGGINS; Fiscal Year: 2016
    ..Defects in segregation lead to aneuploidy, the state where entire chromosomes are gained or lost...
  58. Functional Characterization of Rec104 in Meiotic Recombination
    Isabel Lam; Fiscal Year: 2012
    ..Improper segregation of homologous chromosomes in meiosis I results in aneuploid gametes. Aneuploidy is the leading cause of spontaneous abortions, as well as developmental abnormalities in viable offspring (e.g...
  59. Genetic Dissection of Trisomy 21
    Eugene Yu; Fiscal Year: 2012
    ..It is the most frequent live-born human aneuploidy. It is the most common genetic cause of congenital heart disease and mental retardation...
  60. JOHN RICHARD MCINTOSH; Fiscal Year: 2016
    ..us to understand the disease conditions in which accurate chromosome segregation fails, as in the development of aneuploidy. Our work may also help to identify kinetochore proteins that are likely to be valuable targets for the ..
  61. Mark J Solomon; Fiscal Year: 2016
    ..roles in the responses of cells to many anti-cancer agents and in the mis-segregation of chromosomes leading to aneuploidy and the development of tumors...
  62. Dissection of the Inner Centromere Regulatory Network
    P Todd Stukenberg; Fiscal Year: 2013
    ..The failure of chromosomes to biorient is a major cause of cellular aneuploidy, a driving force in cancer and birth defects...
  63. Molecular Architecture of the Regional Kinetochore in Fission Yeast
    Xiangwei He; Fiscal Year: 2012
    ..Aberrant function of kinetochore leads to aneuploidy, a major form of genetic instability implicated with a number of diseases, in particular, cancers...
  64. Novel Informatics for Highly Reliable Multi-Locus Allele Calling for Embryo Scree
    Matthew Rabinowitz; Fiscal Year: 2009
    ..techniques are unregulated, expensive and highly unreliable: error rates for screening disease-linked loci or aneuploidy are on the order of 10%;each screening test costs more than $5,000;and a couple is forced to choose between ..
  65. Comparative and functional proteomics of germline chromatin in C. elegans
    KENNETH HILLERS; Fiscal Year: 2009
    ..elegans to identify proteins involved in gamete production. Information gained from these studies may help with diagnosis and/or treatment of human reproductive problems. ..
  66. Comprehensive aneuploidy diagnosis in single cells
    Nury Steuerwald; Fiscal Year: 2005
    ..g. aneuploidy) in isolated cells...
  67. P53 AND DNA PLOIDY IN BARRETT'S METAPLASIA
    Mamoun Younes; Fiscal Year: 2005
    ..with Barrett's metaplasia (BM) can be improved by: 1) testing the hypothesis that p53 protein accumulation, DNA aneuploidy, and increased G0G1 or G2M fractions are more accurate and objective markers of malignant potential in Barrett's ..
  68. Control of Genomic Stability by Emi1 and Securin
    NORMAN LEHMAN; Fiscal Year: 2007
    b>Aneuploidy and chromosomal aberrations are common features of human neuroplasms...
  69. CHROMOSOME PAIRING AND NONDISJUNCTION IN HUMAN MEIOSIS
    Edith Cheng; Fiscal Year: 2000
    ..are to determine by fluorescent in situ hybridization (FISH) the pairing behavior and the level of gametic aneuploidy of specific chromosomes in human female germ cells from fetal life to the menopausal period...