On the Sequencing of the Human Genome
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Genomics and Its Impact on Science and Society: the Human Genome Project and Beyond
DOE/SC-0083 Genomics and Its Impact on Science and Society The Human Genome Project and Beyond U.S. Department of Energy Genome Research Programs: genomics.energy.gov A Primer ells are the fundamental working units of every living system. All the instructions Cneeded to direct their activities are contained within the chemical DNA (deoxyribonucleic acid). DNA from all organisms is made up of the same chemical and physical components. The DNA sequence is the particular side-by-side arrangement of bases along the DNA strand (e.g., ATTCCGGA). This order spells out the exact instruc- tions required to create a particular organism with protein complex its own unique traits. The genome is an organism’s complete set of DNA. Genomes vary widely in size: The smallest known genome for a free-living organism (a bac- terium) contains about 600,000 DNA base pairs, while human and mouse genomes have some From Genes to Proteins 3 billion (see p. 3). Except for mature red blood cells, all human cells contain a complete genome. Although genes get a lot of attention, the proteins DNA in each human cell is packaged into 46 chro- perform most life functions and even comprise the mosomes arranged into 23 pairs. Each chromosome is majority of cellular structures. Proteins are large, complex a physically separate molecule of DNA that ranges in molecules made up of chains of small chemical com- length from about 50 million to 250 million base pairs. pounds called amino acids. Chemical properties that A few types of major chromosomal abnormalities, distinguish the 20 different amino acids cause the including missing or extra copies or gross breaks and protein chains to fold up into specific three-dimensional rejoinings (translocations), can be detected by micro- structures that define their particular functions in the cell. -
A Clone-Array Pooled Shotgun Strategy for Sequencing Large Genomes
Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Perspective A Clone-Array Pooled Shotgun Strategy for Sequencing Large Genomes Wei-Wen Cai,1,2 Rui Chen,1,2 Richard A. Gibbs,1,2,5 and Allan Bradley1,3,4 1Department of Molecular and Human Genetics, 2Human Genome Sequencing Center, and 3Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA A simplified strategy for sequencing large genomes is proposed. Clone-Array Pooled Shotgun Sequencing (CAPSS) is based on pooling rows and columns of arrayed genomic clones,for shotgun library construction. Random sequences are accumulated,and the data are processed by sequential comparison of rows and columns to assemble the sequence of clones at points of intersection. Compared with either a clone-by-clone approach or whole-genome shotgun sequencing,CAPSS requires relatively few library constructions and only minimal computational power for a complete genome assembly. The strategy is suitable for sequencing large genomes for which there are no sequence-ready maps,but for which relatively high resolution STS maps and highly redundant BAC libraries are available. It is immediately applicable to the sequencing of mouse,rat,zebrafish, and other important genomes,and can be managed in a cooperative fashion to take advantage of a distributed international DNA sequencing capacity. Advances in DNA sequencing technology in recent years have Drosophila genome, and the computational requirements to greatly increased the throughput and reduced the cost of ge- perform the necessary pairwise comparisons increase approxi- nome sequencing. Sequencing of a complex genome the size mately as a square of the size of the genome (see Appendix). -
From the Human Genome Project to Genomic Medicine a Journey to Advance Human Health
From the Human Genome Project to Genomic Medicine A Journey to Advance Human Health Eric Green, M.D., Ph.D. Director, NHGRI The Origin of “Genomics”: 1987 Genomics (1987) “For the newly developing discipline of [genome] mapping/sequencing (including the analysis of the information), we have adopted the term GENOMICS… ‘The Genome Institute’ Office for Human Genome Research 1988-1989 National Center for Human Genome Research 1989-1997 National Human Genome Research Institute 1997-present NHGRI: Circa 1990-2003 Human Genome Project NHGRI Today: Characteristic Features . Relatively young (~28 years) . Relatively small (~1.7% of NIH) . Unusual historical origins (think ‘Human Genome Project’) . Emphasis on ‘Team Science’ (think managed ‘consortia’) . Rapidly disseminating footprint (think ‘genomics’) . Novel societal/bioethics research component (think ‘ELSI’) . Over-achievers for trans-NIH initiatives (think ‘Common Fund’) . Vibrant (and large) Intramural Research Program A Quarter Century of Genomics Human Genome Sequenced for First Time by the Human Genome Project Genomic Medicine An emerging medical discipline that involves using genomic information about an individual as part of their clinical care (e.g., for diagnostic or therapeutic decision- making) and the other implications of that clinical use The Path to Genomic Medicine ? Human Realization of Genome Genomic Project Medicine Nature Nature Base Pairs to Bedside 2003 Heli201x to 1Health A Quarter Century of Genomics Human Genome Sequenced for First Time by the Human Genome Project -
Probabilities and Statistics in Shotgun Sequencing Shotgun Sequencing
Probabilities and Statistics in Shotgun Sequencing Shotgun Sequencing. Before any analysis of a DNA sequence can take place it is first necessary to determine the actual sequence itself, at least as accurately as is reasonably possible. Unfortunately, technical considerations make it impossible to sequence very long pieces of DNA all at once. Current sequencing technologies allow accurate reading of no more than 500 to 800bp of contiguous DNA sequence. This means that the sequence of an entire genome must be assembled from collections of comparatively short subsequences. This process is called DNA sequence “assembly ”. One approach of sequence assembly is to produce the sequence of a DNA segment (called as a “contig”, or perhaps a genome) from a large number of randomly chosen sequence reads (many overlapping small pieces, each on the order of 500-800 bases). One difficulty of this process is that the locations of the fragments within the genome and with respect to each other are not generally known. However, if enough fragments are sequenced so that there will be many overlaps between them, the fragments can be matched up and assembled. This method is called “ shotgun sequencing .” Shotgun sequencing approaches, including the whole-genome shotgun approach, are currently a central part of all genome-sequencing efforts. These methods require a high level of automation in sample preparation and analysis and are heavily reliant on the power of modern computers. There is an interplay between substrates to be sequenced (genomes and their representation in clone libraries), the analytical tools for generating a DNA sequence, the sequencing strategies, and the computational methods. -
Metagenomics Analysis of Microbiota by Next Generation Shotgun Sequencing
THE SWISS DNA COMPANY Application Note · Next Generation Sequencing Metagenomics Analysis of Microbiota by Next Generation Shotgun Sequencing Understand the genetic potential of your community samples Provides you with hypothesis-free taxonomic analysis Introduction Microbiome studies are often based on as the dependency on a single gene to microbiome analysis overcoming said the sequencing of specific marker genes analyze a whole community, the intro- limitations. Whole genomic DNA of as for instance the prokaryotic 16S rRNA duction of PCR bias and the restriction a sample is isolated, fragmented and gene. Such amplicon-based approaches to describe only the taxonomic compo- finally sequenced. This allows a detailed are well established and widely used. sition and diversity. Shotgun metage- analysis of the taxonomic and functional However, they have limitations such nomics is a cutting edge technique for composition of a microbial community. Microsynth Competences and Services Microsynth offers a full shotgun to your project requirements, thus pro- requirements to guarantee scientifically metagenomics service for taxonomic viding you with just the right amount of reliable results for your project. After and functional profiling of clinical, envi- data to answer your questions. quality processing the reads are aligned ronmental or engineered microbiomes. Bioinformatics: Taxonomic and func- against a protein reference database The service covers the entire process tional analysis of metagenomic data- (e.g. NCBI nr). Taxonomic and functional from experimental design, DNA isola- sets is challenging. Alignment, binning binning and annotation are performed. tion, tailored sequencing to detailed and annotation of the large amounts The analysis is not restricted to prokar- and customized bioinformatics analy- of sequencing reads require expertise yotes but also includes eukaryotes and sis. -
The Economic Impact and Functional Applications of Human Genetics and Genomics
The Economic Impact and Functional Applications of Human Genetics and Genomics Commissioned by the American Society of Human Genetics Produced by TEConomy Partners, LLC. Report Authors: Simon Tripp and Martin Grueber May 2021 TEConomy Partners, LLC (TEConomy) endeavors at all times to produce work of the highest quality, consistent with our contract commitments. However, because of the research and/or experimental nature of this work, the client undertakes the sole responsibility for the consequence of any use or misuse of, or inability to use, any information or result obtained from TEConomy, and TEConomy, its partners, or employees have no legal liability for the accuracy, adequacy, or efficacy thereof. Acknowledgements ASHG and the project authors wish to thank the following organizations for their generous support of this study. Invitae Corporation, San Francisco, CA Regeneron Pharmaceuticals, Inc., Tarrytown, NY The project authors express their sincere appreciation to the following indi- viduals who provided their advice and input to this project. ASHG Government and Public Advocacy Committee Lynn B. Jorde, PhD ASHG Government and Public Advocacy Committee (GPAC) Chair, President (2011) Professor and Chair of Human Genetics George and Dolores Eccles Institute of Human Genetics University of Utah School of Medicine Katrina Goddard, PhD ASHG GPAC Incoming Chair, Board of Directors (2018-2020) Distinguished Investigator, Associate Director, Science Programs Kaiser Permanente Northwest Melinda Aldrich, PhD, MPH Associate Professor, Department of Medicine, Division of Genetic Medicine Vanderbilt University Medical Center Wendy Chung, MD, PhD Professor of Pediatrics in Medicine and Director, Clinical Cancer Genetics Columbia University Mira Irons, MD Chief Health and Science Officer American Medical Association Peng Jin, PhD Professor and Chair, Department of Human Genetics Emory University Allison McCague, PhD Science Policy Analyst, Policy and Program Analysis Branch National Human Genome Research Institute Rebecca Meyer-Schuman, MS Human Genetics Ph.D. -
Randomness Versus Order
MILESTONES DOI: 10.1038/nrg2245 M iles Tone 1 0 Randomness versus order Whereas randomness is avoided used — in their opinion mistakenly The H. influenzae genome, in most experimental techniques, — direct sequencing strategies to however, was a mere DNA fragment it is fundamental to sequencing finish compared with the 1,500-fold longer approaches. In the race to sequence the last 10% of the bacteriophage λ ~3 billion base-pair human genome. the human genome, research groups sequence. In 1991, Al Edwards and In 1996, Craig Venter and colleagues had to choose between the random Thomas Caskey proposed a method proposed that the whole-genome whole-genome shotgun sequencing to maximize efficiency by minimiz- shotgun approach could be used to approach or the more ordered map- ing gap formation and redundancy: sequence the human genome owing based sequencing approach. sequence both ends (but not the to two factors: its past successes When Frederick Sanger and middle) of a long clone, rather than in assembling genomes and the colleagues sequenced the 48-kb the entirety of a short clone. development of bacterial artificial bacteriophage λ genome in 1982, Although the shotgun approach chromosomes (BAC) libraries, which the community was still undecided was now accepted for sequencing allowed large fragments of DNA to as to whether directed or random short stretches of DNA, map-based be cloned. sequencing strategies were better. techniques were still considered A showdown ensued, with the With directed strategies, DNA necessary for large genomes. Like biotechnology firm Celera Genomics sequences were broken down into the directed strategies, map-based wielding whole-genome shotgun ordered and overlapping fragments sequencing subdivided the genome sequencing and the International to build a map of the genome, and into ordered 40-kb fragments, which Human Genome Sequencing these fragments were then cloned were then sequenced using the Consortium wielding map-based and sequenced. -
Evolutionary Genetics
Evolutionary Genetics Ruben C. Arslan & Lars Penke Institute of Psychology Georg August University Göttingen Forthcoming in D. M. Buss (Ed.), Handbook of Evolutionary Psychology (2nd ed.). New York: Wiley. September 17, 2014 Corresponding author: Ruben C. Arslan Georg August University Göttingen Biological Personality Psychology and Psychological Assessment Georg Elias Müller Institute of Psychology Goßlerstr. 14 37073 Göttingen, Germany Tel.: +49 551 3920704 Email: [email protected] 1 Introduction When Charles Darwin developed the theory of evolution, he knew nothing about genetics. Hence, one of its biggest weaknesses was that Darwin had to base it on crude ideas of inheritance. Around the same time, Gregor Mendel discovered the laws of inheritance, but the scientific community initially failed to appreciate his work’s importance. It was only in the 1930’s that Dobzhansky, Fisher, Haldane, Wright, Mayr and others unified genetics and the theory of evolution in the ‘modern synthesis’. Still, the modern synthesis was built on a basic understanding of genetics, with genes merely being particulate inherited information. The basics of molecular genetics, like the structure of DNA, were not discovered until the 1950’s. When modern evolutionary psychology emerged from ethology and sociobiology in the late 1980’s, it had a strong emphasis on human universals, borne from both the assumption that complex adaptations are monomorphic (or sexually dimorphic) and have to go back to at least the last common ancestor of all humans, and the methodological proximity to experimental cognitive psychology, which tends to treat individual differences as statistical noise. As a consequence, genetic differences between people were marginalized in evolutionary psychology (Tooby & Cosmides, 1990). -
Shotgun Metagenomics, from Sampling to Sequencing and Analysis Christopher Quince1,^, Alan W
Shotgun metagenomics, from sampling to sequencing and analysis Christopher Quince1,^, Alan W. Walker2,^, Jared T. Simpson3,4, Nicholas J. Loman5, Nicola Segata6,* 1 Warwick Medical School, University of Warwick, Warwick, UK. 2 Microbiology Group, The Rowett Institute, University of Aberdeen, Aberdeen, UK. 3 Ontario Institute for Cancer Research, Toronto, Canada 4 Department of Computer Science, University of Toronto, Toronto, Canada. 5 Institute for Microbiology and Infection, University of Birmingham, Birmingham, UK. 6 Centre for Integrative Biology, University of Trento, Trento, Italy. ^ These authors contributed equally * Corresponding author: Nicola Segata ([email protected]) Diverse microbial communities of bacteria, archaea, viruses and single-celled eukaryotes have crucial roles in the environment and human health. However, microbes are frequently difficult to culture in the laboratory, which can confound cataloging members and understanding how communities function. Cheap, high-throughput sequencing technologies and a suite of computational pipelines have been combined into shotgun metagenomics methods that have transformed microbiology. Still, computational approaches to overcome challenges that affect both assembly-based and mapping-based metagenomic profiling, particularly of high-complexity samples, or environments containing organisms with limited similarity to sequenced genomes, are needed. Understanding the functions and characterizing specific strains of these communities offer biotechnological promise in therapeutic discovery, or innovative ways to synthesize products using microbial factories, but can also pinpoint the contributions of microorganisms to planetary, animal and human health. Introduction High throughput sequencing approaches enable genomic analyses of ideally all microbes in a sample, not just those that are more amenable to cultivation. One such method, shotgun metagenomics, is the untargeted (“shotgun”) sequencing of all (“meta”) of the microbial genomes (“genomics”) present in a sample. -
Genetics As Explanation: Limits to the Human Genome Project’ (2006, 2009)
els a0026653.tex V2 - 08/29/2016 4:00 P.M. Page 1 Version 3 a0026653 Genetics as Explanation: Introductory article Article Contents Limits to the Human • Definitions • Metaphors and Programs Genome Project • Metaphors and Expectations • Genome is Not a Simple Program Irun R Cohen, The Weizmann Institute of Science, Rehovot, Israel • Microbes, Symbiosis and the Holobiont Henri Atlan, Ecole des Hautes Etudes en Sciences Sociales, Paris, France and Hadas- • Stem Cells Express Multiple Genes • sah University Hospital, Jerusalem, Israel Meaning: Line or Loop? AU:1 • Self-Organisation and Program Sol Efroni, Bar-Ilan University, Ramat Gan, Israel • Complexity, Reduction and Emergence • Evolving Genomes AU:2 Based in part on the previous versions of this eLS article ‘Genetics as Explanation: Limits to the Human Genome Project’ (2006, 2009). • The Environment and the Genome • Language Metaphor • Tool and Toolbox Metaphors • Conclusion Online posting date: 14th October 2016 Living organisms are composed of cells and all biological evolution, single organisms, populations of organisms, living cells contain a genome, the organism’s stock species, cells and molecules, heredity, embryonic development, of deoxyribonucleic acid (DNA). The role of the health and disease and life management. These are quite diverse genome has been likened to a computer program subjects, and the people who study them would seem to use the term gene in distinctly different ways. But genetics as a whole that encodes the organism’s development and its is organised by a single unifying principle, the deoxyribonucleic subsequent response to the environment. Thus, the acid (DNA) code; all would agree that the information borne by organism and its fate can be explained by genetics, a gene is linked to particular sequences of DNA. -
The Human Genome Project: Frequently Asked Questions
The Human Genome Project: Frequently Asked Questions On April 14, 2003, the National Human Genome Research Institute (NHGRI), the Department of Energy (DOE) and their partners in the International Human Genome Sequencing Consortium announced the successful completion of the Human Genome Project. What is a genome? A genome is an organism's complete set of deoxyribonucleic acid (DNA), a chemical compound that contains the genetic instructions needed to develop and direct the biological activities of every organism. DNA molecules are made of two twisting, paired strands. Each strand is made of four chemical units, called nucleotide bases. The bases are adenine (A), thymine (T), guanine (G) and cytosine (C). Bases on opposite strands pair specifically: an A always pairs with a T, and a C always with a G. The human genome contains approximately 3 billion of these base pairs, which reside in the 23 pairs of chromosomes within the nucleus of all our cells. The Human Genome’s Project’s principal task was determining the order or sequence of those As, Ts, Cs, and Gs. What is sequencing and how do you sequence a genome? Sequencing means determining the exact order of the base pairs in a segment of DNA. Human chromosomes range in size from about 50 million to 300 million base pairs. One complete set of genomic instructions is about 3 billion base pairs. Specialized machines called DNA sequencers – the technologies have rapidly evolved over the last decade – use techniques of biochemistry to automatically determine the base pair order and deposit the read out in a computer. -
Genomics and Human Identity Grades 7-12
Genomics and Human Identity Grades 7-12 Lesson 1 Inspired by the museum exhibit Genome: Unlocking Life’s Code unlockinglifescode.org Smithsonian National Museum of Natural History Genomics and Human Identity: Lesson 1 Genomics and Human Identity: Lesson Table of Contents Table of Contents.................................................................................................................2 About the Genomics and Human Identity lessons ..................................................3 Introduction to Lesson 1 – Alike and Different .........................................................3 Lesson Components ............................................................................................................4 Time .........................................................................................................................................4 Key Concepts .........................................................................................................................4 Learning Objectives ............................................................................................................4 Next Generation Science Standards .............................................................................4 Prerequisite Knowledge ....................................................................................................5 Materials and Handouts ....................................................................................................5 Preparation ............................................................................................................................6