DOCSLIB.ORG

The Human Genome Project and Patenting Dna Sequences

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

THE HUMAN GENOME PROJECT AND PATENTING DNA SEQUENCES April 1994 Office of Technology Assessment U.S. Congress CONTENTS* Chapter 1 Summary and Congressional Options** Chapter 2 Introduction Chapter 3 Patent Issues Chapter 4 Ethical Considerations Chapter 5 Research and Development Implications Chapter 6 Federal Technology Transfer *The final report will include several appendixes, such as a list of acronyms, a glossary, acknowledgements, methodologies, lists of contract papers and workshops, and an index. Additionally, a copy editor will review the manuscript, photos will be added, and references will be converted to numbers, based on an alpha list for each chapter. **Also printed as a separate document, with a bibliography of selected references from the full report that might be of interest, as well as available, to the general reader. CHAPTER 1 SUMMARY AND CONGRESSIONAL OPTIONS 1-1 Contents WHY PATENT DNA? ..............................................................1-4 What is DNA? ...............................................................1-5 What is a Patent? .............................................................1-6 Why the Controversy? .........................................................1-9 Who are the Stakeholders? ....................................................1-10 ETHICAL CONSIDERATIONS .....................................................1-11 IMPLICATIONS FOR RESEARCH AND DEVELOPMENT ...............................1-12 FEDERAL TECHNOLOGY TRANSFER ..............................................1-14 WHAT IS THE ROLE OF CONGRESS? ...............................................1-16 PROSPECTS FOR THE FUTURE ....................................................1-38 Boxes 1-A. Terminology ................................................................1-41 1-B. The National Institutes of Health's DNA Patent Application .............................1-42 1-C. The Human Genome Diversity Project ............................................1-44 1-D. Federal Technology Transfer Laws ...............................................1-45 Figures 1-1. Structure of DNA ...........................................................1-47 1-2. Gene Expression ............................................................1-48 Tables 1-1. The Science and Politics of Patenting DNA .........................................1-49 1-2. Patents Involving Human DNA Sequences ......................................... 1-3. Researchers' Reasons for Disapproval of NIH Patent Application ........................1-50 1-4. Researchers' Assessment of Impact of Commercialization on Academic Research ............1-51 1-5. U.S. Companies Involved in Sequencing and Mapping the Human Genome .................1-52 1-6. Summary of Policy Issues and Options for Congress ..................................1-53 1-2 It is the role of Congress, not this Court, to broaden or narrow the reach of the patent laws. This is especially true where . the composition sought to be patented uniquely implicates matters of public concern. Justice William Brennan Diamond v. Chakrabarty (1980) As the 21st century approaches, Congress and the executive branch have committed to funding scientific research and technological developments to determine the location of all human genes. Scientists around the world have undertaken the Human Genome Project--an estimated 15- year, $3 billion initiative--with the expectation that it will both advance basic knowledge, as well as improve genetic diagnoses and enhance therapies. Against the backdrop of this scientific effort, comes the realization that intellectual property law, which provides an exclusive property interest in the work of the mind, is of increasing importance to parties conducting genome research. Beginning in summer 1991 and through the next several months, the National Institutes of Health (NIH) applied for patents on thousands of human DNA sequences believed to represent approximately 5 percent of all human genes (box 1-A). Reaction to the NIH application was swift and largely negative, both in the United States and abroad. NIH’s action sparked widespread debate about the legal issues related to patentability, ethical considerations of patenting human DNA sequences, implications for research and development, and economic issues of technology transfer. In many respects, the ensuring discussion reflected existing questions about the commercialization of biomedical research, but was magnified because of the NIH move’s scope and breadth. Concern about the ethical, social, legal, economic, and scientific implications of intellectual property protection and the Human Genome Project led Senator Edward M. Kennedy, Chairman, Committee on Labor and Human Resources; Senator Mark O. Hatfield, Ranking Minority Member, Committee on Appropriations; and Senator Dennis DeConcini, Chairman, Subcommittee on Patents, 1-3 Copyrights, and Trademarks, Committee on the Judiciary to request this Office of Technology Assessment (OTA) report. The request also reflects longstanding congressional interest in genetics and biotechnology (table l-l). And, though NIH abandoned its application in February 1994, intellectual property protection, specifically--and ethical, legal, and social issues (ELSI), generally--of the Human Genome Project remain public policy issues: Since funding the Human Genome Project, Congress has appropriated more than $21 million to NIH and the U.S. Department of Energy’s (DOE) for extramural grants to study the ethical, legal, and social ramifications of the Human Genome Project. This report focuses on issues arising from patenting human DNA sequences and does not analyze the potential impact of patenting nonhuman DNA sequences--though some of the issues apply generically in considering intellectual property protection of DNA from other sources. Nevertheless, several aspects differ--e.g., ethical considerations of patenting plant or animal DNA--and exploring such differences was not possible for this assessment. Also beyond the scope of this report is an evaluation of the Human Genome Project per se and the use of information derived from it; OTA has analyzed applications of genome research elsewhere. WHY PATENT DNA? Molecular biological research and the industrial sector it spawned, biotechnology, is likely to be the principal scientific driving force for the discovery of new drugs as we enter the 21st century. The potential impact of molecular genetics on the discovery of new therapeutic entities significant. Still, human DNA sequence patents clearly had been granted prior to the NIH application (table 1-2 (pending). Why did controversy arise and who are the stakeholders? 1-4 What Is DNA? DNA, or deoxyribonucleic acid, is a chemical molecule that serves as the repository of genetic information in most living organisms. Through DNA, heritable information is passed from generation to generation. Its structure resembles a twisted ladder, referred to as a double helix (figure l-l) and consists, in part, of four chemical subunits commonly called bases. These four bases--guanine (G), adenine (A), thymine (T), and cytosine (C)--are the genetic alphabet. The bases pair predictably--A with T, and G with C--to form the double helix structure, and scientists refer to each pairing as a base pair, which also serves as a measurement unit to size DNA fragments. The unique linear order of bases--i.e., the sequence--in the DNA helix serves as the blueprint for an organism. Put differently, the sequence of bases distinguishes one segment of DNA from another, and any function that can be assigned to a particular stretch of DNA derives from the precise order of bases. Changes, or mutations, in DNA sequences can lead to genetic disease. The bridge between DNA’s chemical information and physical realization of its instructions consists of steps that convert the DNA code into biological products. Through a process called gene expression, a DNA sequence for a structural gene ultimately results in formation of a molecule called a protein (figure l-2). Proteins are required for the structure, function, and regulation of all cells, tissues, and organs in the body. Lengths of DNA ranging from fewer than 1,000 to 2 million base pairs comprise a gene, and the DNA sequence determines the composition and nature of the protein product. About 50,000 to 100,000 structural genes--i.e., DNA stretches encoding protein products--are scattered among a matrix of DNA bases that do not encode a protein. In total, over 3.3 billion base pairs constitute the human genome. 1-5 Scientists can isolate segments of DNA and determine the sequence of bases. Knowing the order of the bases does not necessarily equate with knowledge of the DNA segment’s in vivo function. Conversely, knowing only a fragment of a gene sequence can provide scientists with enough information to assign a putative role in vivo. A DNA sequence need not code for a gene product to be useful commercially or in research; the order of bases in and of itself can be valuable. Unique stretches of DNA sequences can serve as markers for disease genes, and hence be used as a diagnostic tool. Other fragments, for which scientists can only speculate about an in vivo function, are useful for paternity or forensic identification. What is a Patent? A patent gives the patent owner a temporary right to exclude all others from making, using, or selling an invention during the term of the patent. Governments grant patents--which have a legal foundation in 15th century Venetian law--under the premise that patents
Recommended publications
  • Download.Cse.Ucsc.Edu/ Early Age of Onset (~2.5 Years) of This PRA Form in Goldenpath/Canfam2/Database/) Using Standard Settings

    Download.Cse.Ucsc.Edu/ Early Age of Onset (~2.5 Years) of This PRA Form in Goldenpath/Canfam2/Database/) Using Standard Settings

    Kropatsch et al. Canine Genetics and Epidemiology (2016) 3:7 DOI 10.1186/s40575-016-0037-x RESEARCH Open Access A large deletion in RPGR causes XLPRA in Weimaraner dogs Regina Kropatsch1*, Denis A. Akkad1, Matthias Frank2, Carsten Rosenhagen3, Janine Altmüller4,5, Peter Nürnberg4,6,7, Jörg T. Epplen1,8 and Gabriele Dekomien1 Abstract Background: Progressive retinal atrophy (PRA) belongs to a group of inherited retinal disorders associated with gradual vision impairment due to degeneration of retinal photoreceptors in various dog breeds. PRA is highly heterogeneous, with autosomal dominant, recessive or X-linked modes of inheritance. In this study we used exome sequencing to investigate the molecular genetic basis of a new type of PRA, which occurred spontaneously in a litter of German short-hair Weimaraner dogs. Results: Whole exome sequencing in two PRA-affected Weimaraner dogs identified a large deletion comprising the first four exons of the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene known to be involved in human retinitis pigmentosa and canine PRA. Screening of 16 individuals in the corresponding pedigree of short-hair Weimaraners by qPCR, verified the deletion in hemizygous or heterozygous state in one male and six female dogs, respectively. The mutation was absent in 88 additional unrelated Weimaraners. The deletion was not detectable in the parents of one older female which transmitted the mutation to her offspring, indicating that the RPGR deletion represents a de novo mutation concerning only recent generations of the Weimaraner breed in Germany. Conclusion: Our results demonstrate the value of an existing DNA biobank combined with exome sequencing to identify the underlying genetic cause of a spontaneously occurring inherited disease.
  • Analysis of Trans Esnps Infers Regulatory Network Architecture

    Analysis of Trans Esnps Infers Regulatory Network Architecture

    Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 © 2014 Anat Kreimer All rights reserved ABSTRACT Analysis of trans eSNPs infers regulatory network architecture Anat Kreimer eSNPs are genetic variants associated with transcript expression levels. The characteristics of such variants highlight their importance and present a unique opportunity for studying gene regulation. eSNPs affect most genes and their cell type specificity can shed light on different processes that are activated in each cell. They can identify functional variants by connecting SNPs that are implicated in disease to a molecular mechanism. Examining eSNPs that are associated with distal genes can provide insights regarding the inference of regulatory networks but also presents challenges due to the high statistical burden of multiple testing. Such association studies allow: simultaneous investigation of many gene expression phenotypes without assuming any prior knowledge and identification of unknown regulators of gene expression while uncovering directionality. This thesis will focus on such distal eSNPs to map regulatory interactions between different loci and expose the architecture of the regulatory network defined by such interactions. We develop novel computational approaches and apply them to genetics-genomics data in human. We go beyond pairwise interactions to define network motifs, including regulatory modules and bi-fan structures, showing them to be prevalent in real data and exposing distinct attributes of such arrangements. We project eSNP associations onto a protein-protein interaction network to expose topological properties of eSNPs and their targets and highlight different modes of distal regulation.
  • The Patentability of Synthetic Organisms

    The Patentability of Synthetic Organisms

    Creating Life from Scratch: The Patentability of Synthetic Organisms Michael Saunders* I. INTRODUCTION ................................................................................... 75 II. PATENTING MICROBIAL LIFE—CHAKRABARTY ................................ 77 III. PATENTING MULTICELLULAR LIFE—HARVARD ONCOMOUSE .......... 80 IV. IMPLICATIONS FOR SYNTHETIC BIOLOGY .......................................... 83 A. Single-Celled Synthetic Organisms ......................................... 83 B. Multicellular Synthetic Organisms .......................................... 86 V. CONCLUSIONS ..................................................................................... 88 I. INTRODUCTION Published in May 2007, U.S. application no. 20070122826 (Venter patent) describes a minimally operative genome of the bacterium Mycoplasma genitalium consisting of 381 genes, which the inventors believe to be essential for the survival of the bacterium in an environment containing all the necessary nutrients and free from stress.1 However, the team of inventors from the J. Craig Venter Institute is trying to accomplish something more than just the usual patenting of genes; they intend to create and patent the world’s first artificial organism. The team has already cleared two of the three major hurdles on its way to constructing this first synthetic organism. In January 2008, they announced completion of the second step, the laboratory synthesis of the entire 582,970 base pairs of the genome described in the patent above.2 What remains is the third and final step of inserting this human-made genome into a bacterial cell chassis and “booting up” the organism.3 Craig Venter and Hamilton Smith, lead researchers on the team have been discussing the creation of synthetic life since 1995, when their team published the first complete genome sequence of a living * © 2008 Michael Saunders. J.D. candidate 2009, Tulane University School of Law; B.S. 2003, Bucknell University. 1.
  • Mouse Germ Line Mutations Due to Retrotransposon Insertions Liane Gagnier1, Victoria P

    Mouse Germ Line Mutations Due to Retrotransposon Insertions Liane Gagnier1, Victoria P

    Gagnier et al. Mobile DNA (2019) 10:15 https://doi.org/10.1186/s13100-019-0157-4 REVIEW Open Access Mouse germ line mutations due to retrotransposon insertions Liane Gagnier1, Victoria P. Belancio2 and Dixie L. Mager1* Abstract Transposable element (TE) insertions are responsible for a significant fraction of spontaneous germ line mutations reported in inbred mouse strains. This major contribution of TEs to the mutational landscape in mouse contrasts with the situation in human, where their relative contribution as germ line insertional mutagens is much lower. In this focussed review, we provide comprehensive lists of TE-induced mouse mutations, discuss the different TE types involved in these insertional mutations and elaborate on particularly interesting cases. We also discuss differences and similarities between the mutational role of TEs in mice and humans. Keywords: Endogenous retroviruses, Long terminal repeats, Long interspersed elements, Short interspersed elements, Germ line mutation, Inbred mice, Insertional mutagenesis, Transcriptional interference Background promoter and polyadenylation motifs and often a splice The mouse and human genomes harbor similar types of donor site [10, 11]. Sequences of full-length ERVs can TEs that have been discussed in many reviews, to which encode gag, pol and sometimes env, although groups of we refer the reader for more in depth and general infor- LTR retrotransposons with little or no retroviral hom- mation [1–9]. In general, both human and mouse con- ology also exist [6–9]. While not the subject of this re- tain ancient families of DNA transposons, none view, ERV LTRs can often act as cellular enhancers or currently active, which comprise 1–3% of these genomes promoters, creating chimeric transcripts with genes, and as well as many families or groups of retrotransposons, have been implicated in other regulatory functions [11– which have caused all the TE insertional mutations in 13].
  • Genomics and Its Impact on Science and Society: the Human Genome Project and Beyond

    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.
  • Is BOK Required for Apoptosis Induced by Endoplasmic Reticulum Stress?

    Is BOK Required for Apoptosis Induced by Endoplasmic Reticulum Stress?

    LETTER Is BOK required for apoptosis induced by endoplasmic reticulum stress? LETTER Yuniel Fernandez-Marreroa, Francine Keb,c, Nohemy Echeverrya,1, Philippe Bouilletb,c, Daniel Bachmanna, Andreas Strasserb,c, and Thomas Kaufmanna,2 The B-cell lymphoma 2 (BCL-2)-related ovarian killer comparable Chop levels). Given the critical role of BIM (BOK) shares sequence homology with the proapo- in ER stress-induced apoptosis, this reduction of Bim ptotic BCL-2 family members BAX and BAK. However, may fully account for the reported resistance to ER −/− Bok cells are not protected from classic apoptotic stress. It is unclear whether this reduction of Bim is par- triggers and evidence for a proapoptotic role of BOK ticular to these SV40 MEFs, which are prone to line-to- is derived mostly from overexpression studies (1). BOK line variations within the one genotype, or whether this localizes preferentially to the endoplasmic reticulum is also seen in primary cells (e.g., primary MEFs, which (ER) membrane, where it interacts with IP3-receptors were used for some experiments) from these mice. Im- −/− (2, 3). Using cells from their newly generated Bok portantly, we did not observe significant changes in Bim −/− mouse strain, Carpio et al. propose that BOK is a crit- levels in SV40 MEFs or tissues from our Bok mice (Fig. ical inducer of BAX/BAK-dependent apoptosis in re- 1A). Overall, our analysis of SV40 MEFs, primary MEFs, sponse to ER stress (4). This proposal is in contrast to myeloid progenitors, mast cells, and primary neutrophils our earlier report, in which we showed that loss of BOK did not support a proapoptotic role of BOK downstream did not confer resistance toward ER stress in several of ER stress (2) (Fig.
  • BCL-2 Family Proteins: Changing Partners in the Dance Towards Death

    BCL-2 Family Proteins: Changing Partners in the Dance Towards Death

    Cell Death and Differentiation (2018) 25, 65–80 OPEN Official journal of the Cell Death Differentiation Association www.nature.com/cdd Review BCL-2 family proteins: changing partners in the dance towards death Justin Kale1, Elizabeth J Osterlund1,2 and David W Andrews*,1,2,3 The BCL-2 family of proteins controls cell death primarily by direct binding interactions that regulate mitochondrial outer membrane permeabilization (MOMP) leading to the irreversible release of intermembrane space proteins, subsequent caspase activation and apoptosis. The affinities and relative abundance of the BCL-2 family proteins dictate the predominate interactions between anti-apoptotic and pro-apoptotic BCL-2 family proteins that regulate MOMP. We highlight the core mechanisms of BCL-2 family regulation of MOMP with an emphasis on how the interactions between the BCL-2 family proteins govern cell fate. We address the critical importance of both the concentration and affinities of BCL-2 family proteins and show how differences in either can greatly change the outcome. Further, we explain the importance of using full-length BCL-2 family proteins (versus truncated versions or peptides) to parse out the core mechanisms of MOMP regulation by the BCL-2 family. Finally, we discuss how post- translational modifications and differing intracellular localizations alter the mechanisms of apoptosis regulation by BCL-2 family proteins. Successful therapeutic intervention of MOMP regulation in human disease requires an understanding of the factors that mediate the major binding interactions between BCL-2 family proteins in cells. Cell Death and Differentiation (2018) 25, 65–80; doi:10.1038/cdd.2017.186; published online 17 November 2017 The membrane plays an active role in most BCL-2 family interactions by changing the affinities and local relative abundance of these proteins.
  • 10 Harvard Mouse

    10 Harvard Mouse

    The Harvard Mouse or the transgenetic technique Term Paper Biology Georgina Cibula, 4e LIST of Contents Preface What is my motivation to work on the chosen topic? What is especially interesting? What are our questions with respects to the chosen topic? Introduction What is the context of the chosen topic? What is the recent scientific history? Where and why is the technique used? Are there alternatice treatments? Description of engineering technique No institution visited Discussion What progress was made with the application of the chosen technique? What future research steps? Ethical aspects Summary References PREFACE What is my motivation to work on the chosen topic? There are many reasons. One of them is that it’s a very interesting topic. It is fascinating, how you can increase or decrease the functionality of organisms. What is especially interesting? The intricacy. And that you can use the method not only for mice but for every organism. For example in the Green genetic engineering (to make plants more resistant) or for pharmaceuticals like human insulin. Some genes are responsible for the aging process. So if we can find those genes and deactivate them we would life longer. First successful experiments with animals where already made. What I also like about this topic is the big ethic question behind it. I mean in the end we use animals, often mice because of their similarity to our genes, to benefit of them. We intentional make them ill and lock them into small cages. But on the other hands medicaments can be tested or invented which can save many human lifes.
  • Genetics and Genomics of Human Population Structure 20

    Genetics and Genomics of Human Population Structure 20

    Genetics and Genomics of Human Population Structure 20 Sohini Ramachandran , Hua Tang , Ryan N. Gutenkunst , and Carlos D. Bustamante Abstract Recent developments in sequencing technology have created a fl ood of new data on human genetic variation, and this data has yielded new insights into human popu- lation structure. Here we review what both early and more recent studies have taught us about human population structure and history. Early studies showed that most human genetic variation occurs within populations rather than between them, and that genetically related populations often cluster geographically. Recent studies based on much larger data sets have recapitulated these observations, but have also demonstrated that high-density genotyping allows individuals to be reliably assigned to their population of origin. In fact, for admixed individuals, even the ancestry of particular genomic regions can often be reli- ably inferred. Recent studies have also offered detailed information about the composition of specifi c populations from around the world, revealing how history has shaped their genetic makeup. We also briefl y review quantitative models of human genetic history, including the role natural selection has played in shaping human genetic variation. Contents 20.2.3 Characterizing Locus-Specifi c Ancestry ...................................................... 594 20.1 Introduction ............................................................... 590 20.3 Global Patterns of Human Population Structure ....... 595 20.1.1 Evolutionary Forces Shaping 20.3.1 The Apportionment of Human Human Genetic Variation ........................... 590 Diversity ..................................................... 595 20.2 Quantifying Population Structure ............................. 592 20.3.2 The History and Geography of Human Genes ......................................... 596 20.2.1 FST and Genetic Distance ............................ 592 20.2.2 Model-Based Clustering 20.3.3 Genetic Structure of Human Populations ..
  • Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology

    Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology

    ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database.
  • A Brief History of Human Disease Genetics

    A Brief History of Human Disease Genetics

    Review A brief history of human disease genetics https://doi.org/10.1038/s41586-019-1879-7 Melina Claussnitzer1,2,3, Judy H. Cho4,5,6, Rory Collins7,8, Nancy J. Cox9, Emmanouil T. Dermitzakis10,11, Matthew E. Hurles12, Sekar Kathiresan2,13,14, Eimear E. Kenny4,6,15, Received: 16 July 2019 Cecilia M. Lindgren2,16,17, Daniel G. MacArthur2,13,18, Kathryn N. North19,20, Sharon E. Plon21,22, Accepted: 13 November 2019 Heidi L. Rehm2,13,18,23, Neil Risch24, Charles N. Rotimi25, Jay Shendure26,27,28, Nicole Soranzo12,29 & Mark I. McCarthy17,30,31,32* Published online: 8 January 2020 A primary goal of human genetics is to identify DNA sequence variants that infuence biomedical traits, particularly those related to the onset and progression of human disease. Over the past 25 years, progress in realizing this objective has been transformed by advances in technology, foundational genomic resources and analytical tools, and by access to vast amounts of genotype and phenotype data. Genetic discoveries have substantially improved our understanding of the mechanisms responsible for many rare and common diseases and driven development of novel preventative and therapeutic strategies. Medical innovation will increasingly focus on delivering care tailored to individual patterns of genetic predisposition. medicine, which was previously restricted to a few specific clinical Anniversary indications, is poised to go mainstream. collection: This Review charts recent milestones in the history of human disease go.nature.com/ genetics and provides an opportunity to reflect on lessons learned by nature150 the human genetics community. We focus first on the long-standing division between genetic discovery efforts targeting rare variants with large effects and those seeking alleles that influence predispo- sition to common diseases.
  • Mapping Our Genes—Genome Projects: How Big? How Fast?

    Mapping Our Genes—Genome Projects: How Big? How Fast?

    Mapping Our Genes—Genome Projects: How Big? How Fast? April 1988 NTIS order #PB88-212402 Recommended Citation: U.S. Congress, Office of Technology Assessment, Mapping Our Genes-The Genmne Projects.’ How Big, How Fast? OTA-BA-373 (Washington, DC: U.S. Government Printing Office, April 1988). Library of Congress Catalog Card Number 87-619898 For sale by the Superintendent of Documents U.S. Government Printing Office, Washington, DC 20402-9325 (order form can be found in the back of this report) Foreword For the past 2 years, scientific and technical journals in biology and medicine have extensively covered a debate about whether and how to determine the function and order of human genes on human chromosomes and when to determine the sequence of molecular building blocks that comprise DNA in those chromosomes. In 1987, these issues rose to become part of the public agenda. The debate involves science, technol- ogy, and politics. Congress is responsible for ‘(writing the rules” of what various Federal agencies do and for funding their work. This report surveys the points made so far in the debate, focusing on those that most directly influence the policy options facing the U.S. Congress, The House Committee on Energy and Commerce requested that OTA undertake the project. The House Committee on Science, Space, and Technology, the Senate Com- mittee on Labor and Human Resources, and the Senate Committee on Energy and Natu- ral Resources also asked OTA to address specific points of concern to them. Congres- sional interest focused on several issues: ● how to assess the rationales for conducting human genome projects, ● how to fund human genome projects (at what level and through which mech- anisms), ● how to coordinate the scientific and technical programs of the several Federal agencies and private interests already supporting various genome projects, and ● how to strike a balance regarding the impact of genome projects on international scientific cooperation and international economic competition in biotechnology.