DOCSLIB.ORG

Chromosome Structure Introductory Article

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chromosome Structure Introductory Article Chromosome Structure Introductory article N Patrick Higgins, University of Alabama, Birmingham, Alabama, USA Article Contents . Abundance Genes are organized into discrete cellular structures called chromosomes that coordinate . Chromosome Size DNA replication and distribution of replicated genetic copies between two daughter cells. Plasmids As vehicles of genetic transmission, chromosomes play a central role in Darwinian . Chromosome Shape evolution. Enzymes of DNA Topology . Chromatin Abundance . DNA Replication . Eukaryotic Segregation Biology is divided into three great kingdoms: Eubacteria, . Transcription Archaea and Eukaryota. Bacteria (Eubacteria and Ar- . Recombination chaea) are ubiquitous in the environment, and these small . Chi Sites single-celled organisms grow over an amazingly wide range . Transposons ofenvironmental conditions. For example, bacteria can . Site-specific Recombination grow at temperatures below freezing, and certain members ofthe archaea can grow at depths ofover three miles and at temperatures exceeding 6008F and 200 atmospheres of pressure. Eukaryotes, which include the more conspicuous genome yet analysed is that of Myxococcus xanthus, with fungi and all plants and animals, are usually recognized as 9.2 Mbp (9 200 000 bp). However, the best studied organ- the predominant life forms on earth. They are subjects of ism in nature is E. coli, which has a 4.6-Mbp chromosome great biological interest and they differ from bacteria by with 4288 genes for proteins, seven operons for ribosomal having a larger cell size and by compartmentalizing ribonucleic acids (RNAs), and 86 genes for transfer RNAs. chromosomal deoxyribonucleic acid (DNA) in a nucleus, The E. coli chromosome contains numerous gene which separates it from the protein-making cytoplasm. families, each family having evolved from a common None the less, considering the large cell numbers and wide ancestor. The largest gene family is comprised of 96 three- environmental growth ranges, bacteria easily account for component (ABC) transporters, which are membrane- the majority ofDNA biomass on earth. bound machines that import and export a variety ofsmall The chromosome is the heart ofa central paradox in molecules and proteins. By contrast, the smallest free- evolution. How do species in the three kingdoms remain living organism is Mycoplasma genatalium with a 0.58- the same over long periods ofgeological time and also Mbp genome that encodes 468 protein genes, one generate sufficient variability to produce new species, ribosomal RNA operon and one ABC transporter. Both sometimes relatively rapidly? Stability versus change is a E. coli and M. genatalium have complete information for crucial dichotomy in molecular biology. The events that the synthesis ofcell walls, cell membranes and critical bring about stability and change in DNA structure involve enzymes ofintermediary metabolism, plus the RNA processes ofreplication, transcription and recombination. molecules, ribosomal proteins and a clutch ofenzymes Similar mechanisms operate in the three living kingdoms, (the replisome) to replicate DNA efficiently. Putative but the key molecular mechanisms that control and functions for about a quarter of the genes of E. coli remain catalyse these events are understood best in a eubacterium: to be discovered. A reasonable estimate is that 150–200 Escherichia coli. protein-encoding genes would be ‘essential’ for a basic bacterial lifestyle (in a rich medium). Eukaryotic organisms generally have larger chromo- somes than bacteria. For example, the yeast Saccharo- myces cerevisiae has about 6000 genes (50% more than E. Chromosome Size coli), whereas mammalian cells contain 1000 times (per haploid equivalent) the DNA ofan E. coli cell. In humans Free-living bacteria need genetic information to synthesize the 5000 Mbp ofhaploid DNA is distributed among 22 proteins for executing vital functions. Most bacteria have a autosomes and two sex-specific chromosomes. Eukaryotic single chromosome with DNA that is about 2 Mbp (mega DNA is localized in a compartment, the nucleus, which is base pairs) long (1 Mbp 5 1 000 000 base pairs), but the separated by a phospholipid-containing membrane from DNA content ofdifferent species varies from0.58 to cytoplasmic ribosomes and protein translation activity. greater than 9 Mbp ofDNA, and some bacteria have During cell division, the eukaryotic nuclear membrane multiple chromosomes. For example, Leptospira has two chromosomes of4.4 and 4.6 Mbp and the largest bacterial ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Macmillan Publishers Ltd, Nature Publishing Group / www.els.net 1 Chromosome Structure breaks down once per cell cycle to distribute the 46 diploid Plectonemic Paranemic chromosomes equally between two daughter cells. Plasmids 5kbp In addition to the large chromosome, many (most?) Plasmid bacteria have additional DNA molecules called plasmids (or episomes.) Plasmids are separate DNA molecules that contain a replication origin which allows them to multiply independently ofthe host chromosome. Plasmids range in size from 1 kbp (Kilo base pair) (1000 bp) to 100 kbp, and these DNA molecules encode genetic systems for specia- Eukaryotic chromatin Prokaryotic chromatin lized functions. Some plasmids make extracellular appen- Gyrase dages that allow bacteria to infect and colonize sensitive Histone eukaryotic hosts. Plasmids often carry genes that confer on Solenoidal assembly bacteria the ability to survive in the presence ofantibiotics supercoils σ such as tetracycline, kanamycin and penicillin. Many = –0.05 HU H-NS plasmids also contain genes that promote DNA transfer so Deproteinate that plasmid genes can move into other bacterial species. Plasmid transfer has caused the emergence of bacterial pathogens that are resistant to most ofthe useful Interwound antibiotics in medicine, with notable examples including supercoils (a) σ = –0.05 multidrug-resistant strains of Staphylococcus and Myco- bacterium tuberculosis. In most eukaryotes, plasmids are rare. However, S. Topo cerevisiae contains a plasmid called the 2-m circle which IV efficiently partitions to new daughter cells at every cell Topo division. This DNA serves as a convenient module for gene II cloning and performing genetic experiments in yeast. (b) Figure 1 (a) DNA is a plectonemic helix (left) rather than a paranemic helix (right), and thus it must spin axially to undergo replication, transcription and extended pairing for homologous recombination. Chromosome Shape Supercoiling in circular bacterial chromosomes is maintained by the concerted action of DNA gyrase, which introduces negative supercoils at On a macroscopic scale, bacterial chromosomes are either the expense of adenosine triphosphate (ATP) binding and hydrolysis, and circular or linear. Circular chromosomes are most TopoI plus TopoII, which remove excess negative supercoils. Negative common, at least among the best-studied bacteria. How- supercoiled DNA adopts an interwound conformation. However, ‘solenoidal’ supercoils can be stabilized when DNA is wrapped on a protein ever, the causative agent ofLyme disease, Borrelia surface. This is the mechanism of supercoil formation in mammalian cells burgdorphei, has a 2-Mb linear chromosome plus 12 (centre left). Most bacteria have nonspecific DNA-binding proteins such as different linear plasmids. Eukaryotic chromosomes are HU and H-NS, which stabilize supercoils but are much less effective at invariably linear, and they have two ends, each carrying a condensing DNA compared with true histones (centre right). (b) Bacteria special structure called a telomere, and a organized region and eukaryotes both have an enzyme, TopoIV and TopoII respectively, designed to unknot and untangle DNA. called the centromere which allows the chromosome to attach to cellular machinery that moves it to the proper place during cell division. DNA synthesis the rotation speed approaches 6000 rpm. One critical facet of chromosome structure is that DNA Chromosomal DNA molecules are very long and thin, so is a plectonemic helix, which means that two helical strands DNA must fold many times to fit within the confines of a entwine about each other. For duplex DNA the two bacterial cell. How does DNA twisting transpire without antiparallel strands, often referred to as the Watson and chromosomes getting tangled up? The problem was Crick (red and blue in Figure 1), are interwound once for important enough that Watson and Crick considered a every 10 bp. Because ofthis wound configuration, bio- paranemic helix, which is a pair ofcoils that lay side by side chemical transactions that involve strand separation without interwinding. Strands ofa paranemic helix can require chromosome movement (spin) about DNA’s long separate without rotation (Figure 1). None the less DNA is axis. The processes ofDNA replication, recombination plectonemic, and keeping chromosomes untangled re- and transcription all require DNA rotation, and during quires a special class ofenzymes called topoisomerases. 2 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Macmillan Publishers Ltd, Nature Publishing Group / www.els.net Chromosome Structure Enzymes of DNA Topology enzyme such as gyrase, eukaryotic DNA is wrapped tightly around nucleosomes, generating solenoidal supercoils that The enzymes that solve the untangling problem are condense DNA 8-fold (Figure 1). A nucleosome contains topoisomerases. Topoisomerases break and rejoin DNA four subunits: histones H2A, H2B, H3 and H4. If histones molecules, thereby allowing individual strands to pass
Load more

Recommended publications
  • Distinct Visual Pathways Mediatedrosophilalarval Light
    The Journal of Neuroscience, April 27, 2011 • 31(17):6527–6534 • 6527 Behavioral/Systems/Cognitive Distinct Visual Pathways Mediate Drosophila Larval Light Avoidance and Circadian Clock Entrainment Alex C. Keene,1 Esteban O. Mazzoni,1 Jamie Zhen,1 Meg A. Younger,1 Satoko Yamaguchi,1 Justin Blau,1 Claude Desplan,1 and Simon G. Sprecher1,2 1Department of Biology, Center for Developmental Genetics, New York University, New York, New York 10003-6688, and 2Department of Biology, Institute of Cell and Developmental Biology, University of Fribourg, 1700 Fribourg, Switzerland Visual organs perceive environmental stimuli required for rapid initiation of behaviors and can also entrain the circadian clock. The larval eye of Drosophila is capable of both functions. Each eye contains only 12 photoreceptors (PRs), which can be subdivided into two subtypes. Four PRs express blue-sensitive rhodopsin5 (rh5) and eight express green-sensitive rhodopsin6 (rh6). We found that either PR-subtype is sufficient to entrain the molecular clock by light, while only the Rh5-PR subtype is essential for light avoidance. Acetylcholine released from PRs confers both functions. Both subtypes of larval PRs innervate the main circadian pacemaker neurons of the larva, the neuropeptide PDF (pigment-dispersing factor)-expressing lateral neurons (LNs), providing sensory input to control circadian rhythms. How- ever, we show that PDF-expressing LNs are dispensable for light avoidance, and a distinct set of three clock neurons is required. Thus we have identifieddistinctsensoryandcentralcircuitryregulatinglightavoidancebehaviorandclockentrainment.Ourfindingsprovideinsightsintothe coding of sensory information for distinct behavioral functions and the underlying molecular and neuronal circuitry. Introduction sin6 (rh6) (Sprecher et al., 2007; Sprecher and Desplan, 2008).
    [Show full text]
  • Genome Analysis and Knowledge
    Dahary et al. BMC Medical Genomics (2019) 12:200 https://doi.org/10.1186/s12920-019-0647-8 SOFTWARE Open Access Genome analysis and knowledge-driven variant interpretation with TGex Dvir Dahary1*, Yaron Golan1, Yaron Mazor1, Ofer Zelig1, Ruth Barshir2, Michal Twik2, Tsippi Iny Stein2, Guy Rosner3,4, Revital Kariv3,4, Fei Chen5, Qiang Zhang5, Yiping Shen5,6,7, Marilyn Safran2, Doron Lancet2* and Simon Fishilevich2* Abstract Background: The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient’s phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. Results: We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex’s main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex’s broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards’ recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters.
    [Show full text]
  • Metabolic Inactivation of the Circadian Transmitter, Pigment Dispersing Factor (PDF), by Neprilysin-Like Peptidases in Drosophila R
    4465 The Journal of Experimental Biology 210, 4465-4470 Published by The Company of Biologists 2007 doi:10.1242/jeb.012088 Metabolic inactivation of the circadian transmitter, pigment dispersing factor (PDF), by neprilysin-like peptidases in Drosophila R. Elwyn Isaac1,*, Erik C. Johnson2, Neil Audsley3 and Alan D. Shirras4 1Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK, 2Department of Biology, Wake Forest University, NC, USA, 3Central Science Laboratory, Sand Hutton, York, YO41 1LZ, UK and 4Department of Biological Sciences, University of Lancaster, LA1 4YQ, UK *Author for correspondence (e-mail: [email protected]) Accepted 4 October 2007 Summary Recent studies have firmly established pigment confirming that such cleavage results in PDF inactivation. dispersing factor (PDF), a C-terminally amidated The Ser7–Leu8 peptide bond was also the principal octodecapeptide, as a key neurotransmitter regulating cleavage site when PDF was incubated with membranes rhythmic circadian locomotory behaviours in adult prepared from heads of adult Drosophila. This Drosophila melanogaster. The mechanisms by which PDF endopeptidase activity was inhibited by the neprilysin –1 functions as a circadian peptide transmitter are not fully inhibitors phosphoramidon (IC50, 0.15·␮mol·l ) and –1 understood, however; in particular, nothing is known thiorphan (IC50, 1.2·␮mol·l ). We propose that cleavage by about the role of extracellular peptidases in terminating a member of the Drosophila neprilysin family of PDF signalling at synapses. In this study we show that PDF endopeptidases is the most likely mechanism for is susceptible to hydrolysis by neprilysin, an endopeptidase inactivating synaptic PDF and that neprilysin might have that is enriched in synaptic membranes of mammals and an important role in regulating PDF signals within insects.
    [Show full text]
  • Analysis of 3D Genomic Interactions Identifies Candidate Host Genes That Transposable Elements Potentially Regulate Ramya Raviram1,2,3†, Pedro P
    Raviram et al. Genome Biology (2018) 19:216 https://doi.org/10.1186/s13059-018-1598-7 RESEARCH Open Access Analysis of 3D genomic interactions identifies candidate host genes that transposable elements potentially regulate Ramya Raviram1,2,3†, Pedro P. Rocha1,4†, Vincent M. Luo1,2, Emily Swanzey5, Emily R. Miraldi2,6,7,8, Edward B. Chuong9, Cédric Feschotte10, Richard Bonneau2,6,7 and Jane A. Skok1* Abstract Background: The organization of chromatin in the nucleus plays an essential role in gene regulation. About half of the mammalian genome comprises transposable elements. Given their repetitive nature, reads associated with these elements are generally discarded or randomly distributed among elements of the same type in genome-wide analyses. Thus, it is challenging to identify the activities and properties of individual transposons. As a result, we only have a partial understanding of how transposons contribute to chromatin folding and how they impact gene regulation. Results: Using PCR and Capture-based chromosome conformation capture (3C) approaches, collectively called 4Tran, we take advantage of the repetitive nature of transposons to capture interactions from multiple copies of endogenous retrovirus (ERVs) in the human and mouse genomes. With 4Tran-PCR, reads are selectively mapped to unique regions in the genome. This enables the identification of transposable element interaction profiles for individual ERV families and integration events specific to particular genomes. With this approach, we demonstrate that transposons engage in long-range intra-chromosomal interactions guided by the separation of chromosomes into A and B compartments as well as topologically associated domains (TADs). In contrast to 4Tran-PCR, Capture-4Tran can uniquely identify both ends of an interaction that involve retroviral repeat sequences, providing a powerful tool for uncovering the individual transposable element insertions that interact with and potentially regulate target genes.
    [Show full text]
  • Reverse Transcriptase Activity Innate to DNA Polymerase I and DNA
    Reverse transcriptase activity innate to DNA SEE COMMENTARY polymerase I and DNA topoisomerase I proteins of Streptomyces telomere complex Kai Bao*† and Stanley N. Cohen*‡§ Departments of *Genetics and ‡Medicine, Stanford University School of Medicine, Stanford, CA 94305-5120 Edited by Nicholas R. Cozzarelli, University of California, Berkeley, CA, and approved August 10, 2004 (received for review June 18, 2004) Replication of Streptomyces linear chromosomes and plasmids gation and, remarkably, that both of these eubacterial enzymes -proceeds bidirectionally from a central origin, leaving recessed 5؅ can function efficiently as RTs in addition to having the bio termini that are extended by a telomere binding complex. This chemical properties predicted from their sequences. We further complex contains both a telomere-protecting terminal protein show that the Streptomyces coelicolor and Streptomyces lividans (Tpg) and a telomere-associated protein that interacts with Tpg TopA proteins are prototypes for a subfamily of bacterial and the DNA ends of linear Streptomyces replicons. By using topoisomerases whose catalytic domains contain a unique Asp– histidine-tagged telomere-associated protein (Tap) as a scaffold, Asp doublet motif that is required for their RT activity and which we identified DNA polymerase (PolA) and topoisomerase I (TopA) is essential also to the RNA-dependent DNA polymerase func- proteins as other components of the Streptomyces telomere com- tions of HIV RT and eukaryotic cell telomerases (16, 17). plex. Biochemical characterization of these proteins indicated that both PolA and TopA exhibit highly efficient reverse transcriptase Materials and Methods (RT) activity in addition to their predicted functions. Although RT Plasmid and Bacterial Strains.
    [Show full text]
  • The Human Genome Project
    TO KNOW OURSELVES ❖ THE U.S. DEPARTMENT OF ENERGY AND THE HUMAN GENOME PROJECT JULY 1996 TO KNOW OURSELVES ❖ THE U.S. DEPARTMENT OF ENERGY AND THE HUMAN GENOME PROJECT JULY 1996 Contents FOREWORD . 2 THE GENOME PROJECT—WHY THE DOE? . 4 A bold but logical step INTRODUCING THE HUMAN GENOME . 6 The recipe for life Some definitions . 6 A plan of action . 8 EXPLORING THE GENOMIC LANDSCAPE . 10 Mapping the terrain Two giant steps: Chromosomes 16 and 19 . 12 Getting down to details: Sequencing the genome . 16 Shotguns and transposons . 20 How good is good enough? . 26 Sidebar: Tools of the Trade . 17 Sidebar: The Mighty Mouse . 24 BEYOND BIOLOGY . 27 Instrumentation and informatics Smaller is better—And other developments . 27 Dealing with the data . 30 ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS . 32 An essential dimension of genome research Foreword T THE END OF THE ROAD in Little has been rapid, and it is now generally agreed Cottonwood Canyon, near Salt that this international project will produce Lake City, Alta is a place of the complete sequence of the human genome near-mythic renown among by the year 2005. A skiers. In time it may well And what is more important, the value assume similar status among molecular of the project also appears beyond doubt. geneticists. In December 1984, a conference Genome research is revolutionizing biology there, co-sponsored by the U.S. Department and biotechnology, and providing a vital of Energy, pondered a single question: Does thrust to the increasingly broad scope of the modern DNA research offer a way of detect- biological sciences.
    [Show full text]
  • Development of Adenoviral Vectors for Monitoring Telomerase Activity in Living Cells
    Development of adenoviral vectors for monitoring telomerase activity in living cells Edqvist, Anna 2007 Link to publication Citation for published version (APA): Edqvist, A. (2007). Development of adenoviral vectors for monitoring telomerase activity in living cells. Genetics. Total number of authors: 1 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Download date: 05. Oct. 2021 DEVELOPMENT OF ADENOVIRAL VECTORS FOR MONITORING TELOMERASE ACTIVITY IN LIVING CELLS ANNA HELENA EDQVIST 2007 DEPARTMENT OF CELL AND ORGANISM BIOLOGY LUND UNIVERSITY SWEDEN A doctoral thesis at a university in Sweden is produced either as a monograph or as a collection of papers. In the latter case, the introductory part constitutes the formal thesis, which summarises the accompanying papers.
    [Show full text]
  • Microorganisms
    microorganisms Review Rules and Exceptions: The Role of Chromosomal ParB in DNA Segregation and Other Cellular Processes Adam Kawalek y , Pawel Wawrzyniak y, Aneta Agnieszka Bartosik and Grazyna Jagura-Burdzy * Department of Microbial Biochemistry, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawi´nskiego5a, 02-106 Warsaw, Poland; [email protected] (A.K.); [email protected] (P.W.); [email protected] (A.A.B.) * Correspondence: [email protected]; Tel.: +48-225921212 These authors contributed equally to this work. y Received: 4 December 2019; Accepted: 9 January 2020; Published: 11 January 2020 Abstract: The segregation of newly replicated chromosomes in bacterial cells is a highly coordinated spatiotemporal process. In the majority of bacterial species, a tripartite ParAB-parS system, composed of an ATPase (ParA), a DNA-binding protein (ParB), and its target(s) parS sequence(s), facilitates the initial steps of chromosome partitioning. ParB nucleates around parS(s) located in the vicinity of newly replicated oriCs to form large nucleoprotein complexes, which are subsequently relocated by ParA to distal cellular compartments. In this review, we describe the role of ParB in various processes within bacterial cells, pointing out interspecies differences. We outline recent progress in understanding the ParB nucleoprotein complex formation and its role in DNA segregation, including ori positioning and anchoring, DNA condensation, and loading of the structural maintenance of chromosome (SMC) proteins. The auxiliary roles of ParBs in the control of chromosome replication initiation and cell division, as well as the regulation of gene expression, are discussed. Moreover, we catalog ParB interacting proteins.
    [Show full text]
  • Telomere-Loop Dynamics in Chromosome End Protection
    bioRxiv preprint doi: https://doi.org/10.1101/279877; this version posted March 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Telomere-loop dynamics in chromosome end protection David Van Ly1,2, Ronnie Ren Jie Low1,6, Sonja Frölich1,7, Tara K. Bartolec1,8, Georgia R. Kafer1, Hilda A. Pickett3, Katharina Gaus4,5, and Anthony J. Cesare1,9*. 1Genome Integrity Unit, Children’s Medical Research Institute, University of Sydney, Westmead, New South Wales 2145, Australia. 2 School of Medicine, The University of Notre Dame Australia, Sydney, New South Wales 2010, Australia. 3Telomere Length Regulation Unit, Children’s Medical Research Institute, University of Sydney, Westmead, New South Wales 2145, Australia. 4EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. 5ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, NSW 2052, Australia. 6Current affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia 7Current affiliation: Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia. 8Current affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, 2052, Australia 9Lead contact *Correspondence: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/279877; this version posted March 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Chromosome.Pdf
    Chromosomes What Exactly is a chromosome? Chromosomes are the rod-shaped, filamentous bodies present in the nucleus, which become visible during cell division. They are the carriers of the gene or unit of heredity. Chromosome are not visible in active nucleus due to their high water content, but are clearly seen during cell division. Chromosomes were first described by Strausberger in 1875. The term “Chromosome”, however was first used by Waldeyer in 1888. They were given the name chromosome (Chromo = colour; Soma = body) due to their marked affinity for basic dyes. Their number can be counted easily only during mitotic metaphase. Chromosomes are composed of thin chromatin threads called Chromatin fibers. These fibers undergo folding, coiling and supercoiling during prophase so that the chromosomes become progressively thicker and smaller. Therefore, chromosomes become readily observable under light microscope. At the end of cell division, on the other hand, the fibers uncoil and extend as fine chromatin threads, which are not visible at light microscope Number of chromosomes Normally, all the individuals of a species have the same number of chromosomes. Closely related species usually have similar chromosome numbers. Presence of a whole sets of chromosomes is called euploidy. It includes haploids, diploids, triploids, tetraploids etc. Gametes normally contain only one set of chromosome – this number is called Haploid Somatic cells usually contain two sets of chromosome - 2n : Diploid 3n – triploid 4n – tetraploid The condition in which the chromosomes sets are present in a multiples of “n” is Polyploidy When a change in the chromosome number does not involve entire sets of chromosomes, but only a few of the chromosomes - is Aneuploidy.
    [Show full text]
  • The NIH Catalyst from the Deputy Director for Intramural Research
    — Fostering Communication and Collaboration The nihCatalyst A Publication fob NIH Intramural Scientists National Institutes of Health i Office of the Director Volume 8, Issue 6 November-December 2000 NIH Research Festival Translational Research Running with the Genome: Jean Li d Cadet: NIH Gets To Work with the ‘Working Draft’ A Bridge at NIDA by Cynthia Delgado by Fran Pollner he “working draft” se- r ean Lud Cadet is equally at home quence of the human I upstairs and downstairs in the genome, delivered to building that houses the NIDA in- T | the desktops of the biomedi- Jamural research program at the cal community this summer, Johns Hopkins University Bayview may become the most “dog- campus in Baltimore. eared” work-in-progress the On the fourth floor, Cadet runs the world has ever known. four labs that make up the Molecu- Unlike the first draft of a lar Neuropsychiatry Unit, of which medical text that requires cor- he is chief; and on the first floor, he rections and updates before directs NIDA’s clinical research pro- it is finally printed, the gram, overseeing the inpatient re- genome’s first draft is out search unit, the outpatient research there, and some NIH investi- program, an adolescent clinic that fo- gators are using it to make cuses on smoking new discoveries while oth- cessation, and the — ers are arranging the data to 70 currently active make the material even more clinical protocols meaningful as a resource to all of which are the research community. strategic use of the HGP’s data aided conducted on-site.
    [Show full text]
  • Robust Measurement of Telomere Length in Single Cells PNAS PLUS
    Robust measurement of telomere length in single cells PNAS PLUS Fang Wanga,b, Xinghua Panc,1, Keri Kalmbacha, Michelle L. Seth-Smitha, Xiaoying Yeb, Danielle M. F. Antumesa,d,e, Yu Yinb, Lin Liub,1, David L. Keefea,1, and Sherman M. Weissmanc,1 aDepartment of Obstetrics and Gynecology, New York University Langone Medical Center, NY 10016; bState Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; cDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005; dDepartment of Pathology, Fluminense Federal University, 24033-900, Rio de Janeiro, Brazil; and eCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) Foundation, Ministry of Education of Brazil, 70040-020, Brasilia, Brazil Contributed by Sherman M. Weissman, April 9, 2013 (sent for review February 5, 2013) Measurement of telomere length currently requires a large popula- length for a given cell population (10–12). High-throughput tion of cells, which masks telomere length heterogeneity in single Q-FISH, flow FISH, and single telomere length analysis can be used cells, or requires FISH in metaphase arrested cells, posing technical for telomere measurement of dividing, nondividing, and senescent challenges. A practical method for measuring telomere length in cells, but these methods also require large cell populations (13–15). single cells has been lacking. We established a simple and robust The ability to measure telomere length in single cells rather approach for single-cell telomere length measurement (SCT-pqPCR). than relying upon average telomere length in cell populations or We first optimized a multiplex preamplification specific for telo- the entire tissue enables the study of biological heterogeneity on meres and reference genes from individual cells, such that the ampli- a cell-by-cell basis, an issue of fundamental importance for studies con provides a consistent ratio (T/R) of telomeres (T) to the reference of aging, development, carcinogenesis, and many other diseases.
    [Show full text]