Human Genome Project

The Human Genome Project (HGP) was an international scientific research project with the goal of determining the sequence of nucleotide base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint.[1] It remains the world's largest collaborative biological project.[2] After the idea was picked up in 1984 by the US government when the planning started, the project formally launched in 1990 and was declared complete on April 14, 2003.[3] Funding came from the US government through the National Institutes of Health (NIH) as well as numerous other groups from around the world. A parallel project was conducted outside government by the Celera Corporation, or Celera Genomics, which was formally launched in 1998. Most of the government-sponsored sequencing was performed in twenty universities and research centers in the United States, the United Kingdom, Japan, France, Germany and China.[4]

The Human Genome Project originally aimed to map the nucleotides contained in a human haploid reference genome (more than three billion). The "genome" of any given individual is unique; mapping the "human genome" involved sequencing a small number of individuals and then assembling these together to get a complete sequence for each chromosome. Therefore, the finished human genome is a mosaic, not representing any one individual.

Vitruvian man
Logo of the HGP – the Vitruvian Man by Leonardo da Vinci.

Human Genome Project

History

Dna-split

The Human Genome Project was a 15-year-long, publicly funded project initiated in 1990 with the objective of determining the DNA sequence of the entire euchromatic human genome within 15 years.[5] In May 1985, Robert Sinsheimer organized a workshop to discuss sequencing the human genome,[6] but for a number of reasons the NIH was uninterested in pursuing the proposal. The following March, the Santa Fe Workshop was organized by Charles DeLisi and David Smith of the Department of Energy's Office of Health and Environmental Research (OHER).[7] At the same time Renato Dulbecco proposed whole genome sequencing in an essay in Science.[8] James Watson followed two months later with a workshop held at the Cold Spring Harbor Laboratory.

The fact that the Santa Fe workshop was motivated and supported by a Federal Agency opened a path, albeit a difficult and tortuous one,[9] for converting the idea into a public policy in the United States. In a memo to the Assistant Secretary for Energy Research (Alvin Trivelpiece), Charles DeLisi, who was then Director of the OHER, outlined a broad plan for the project.[10] This started a long and complex chain of events which led to approved reprogramming of funds that enabled the OHER to launch the Project in 1986, and to recommend the first line item for the HGP, which was in President Reagan's 1988 budget submission,[9] and ultimately approved by the Congress. Of particular importance in Congressional approval was the advocacy of Senator Peter Domenici, whom DeLisi had befriended.[11] Domenici chaired the Senate Committee on Energy and Natural Resources, as well as the Budget Committee, both of which were key in the DOE budget process. Congress added a comparable amount to the NIH budget, thereby beginning official funding by both agencies.

Alvin Trivelpiece sought and obtained the approval of DeLisi's proposal by Deputy Secretary William Flynn Martin. This chart[12] was used in the spring of 1986 by Trivelpiece, then Director of the Office of Energy Research in the Department of Energy, to brief Martin and Under Secretary Joseph Salgado regarding his intention to reprogram $4 million to initiate the project with the approval of Secretary Herrington. This reprogramming was followed by a line item budget of $16 million in the Reagan Administration’s 1987 budget submission to Congress.[13] It subsequently passed both Houses. The Project was planned for 15 years.[14]

Candidate technologies were already being considered for the proposed undertaking at least as early as 1985.[15]

In 1990, the two major funding agencies, DOE and NIH, developed a memorandum of understanding in order to coordinate plans and set the clock for the initiation of the Project to 1990.[16] At that time, David Galas was Director of the renamed “Office of Biological and Environmental Research” in the U.S. Department of Energy's Office of Science and James Watson headed the NIH Genome Program. In 1993, Aristides Patrinos succeeded Galas and Francis Collins succeeded James Watson, assuming the role of overall Project Head as Director of the U.S. National Institutes of Health (NIH) National Center for Human Genome Research (which would later become the National Human Genome Research Institute). A working draft of the genome was announced in 2000 and the papers describing it were published in February 2001. A more complete draft was published in 2003, and genome "finishing" work continued for more than a decade.

The $3-billion project was formally founded in 1990 by the US Department of Energy and the National Institutes of Health, and was expected to take 15 years.[17] In addition to the United States, the international consortium comprised geneticists in the United Kingdom, France, Australia, China and myriad other spontaneous relationships.[18] Considering the inflation, the project roughly costed $5 billion.[19][20]

Due to widespread international cooperation and advances in the field of genomics (especially in sequence analysis), as well as major advances in computing technology, a 'rough draft' of the genome was finished in 2000 (announced jointly by U.S. President Bill Clinton and the British Prime Minister Tony Blair on June 26, 2000).[21] This first available rough draft assembly of the genome was completed by the Genome Bioinformatics Group at the University of California, Santa Cruz, primarily led by then graduate student Jim Kent. Ongoing sequencing led to the announcement of the essentially complete genome on April 14, 2003, two years earlier than planned.[22][23] In May 2006, another milestone was passed on the way to completion of the project, when the sequence of the last chromosome was published in Nature.[24]

The institutions, companies and laboratories in Human Genome Program are listed below, according to NIH.[25]

No. Nation Name Affiliation
1 United States The Whitehead Institute/MIT Center for Genome Research Massachusetts Institute of Technology
2 United Kingdom The Wellcome Trust Sanger Institute Wellcome Trust
3 United States Washington University School of Medicine Genome Sequencing Center Washington University in St. Louis
4 United States United States DOE Joint Genome Institute United States Department of Energy
5 United States Baylor College of Medicine Human Genome Sequencing Center Baylor College of Medicine
6 Japan RIKEN Genomic Sciences Center Riken
7 France Genoscope and CNRS UMR-8030 French Alternative Energies and Atomic Energy Commission
8 United States GTC Sequencing Center Genome Therapeutics Corporation, whose sequencing division is acquired by ABI
9 Germany Department of Genome Analysis Fritz Lipmann Institute, name changed from Institute of Molecular Biotechnology
10 China Beijing Genomics Institute/Human Genome Center Chinese Academy of Sciences
11 United States Multimegabase Sequencing Center Institute for Systems Biology
12 United States Stanford Genome Technology Center Stanford University
13 United States Stanford Human Genome Center and Department of Genetics Stanford University School of Medicine
14 United States University of Washington Genome Center University of Washington
15 Japan Department of Molecular Biology Keio University School of Medicine
16 United States University of Texas Southwestern Medical Center at Dallas University of Texas
17 United States University of Oklahoma's Advanced Center for Genome Technology Dept. of Chemistry and Biochemistry, University of Oklahoma
18 Germany Max Planck Institute for Molecular Genetics Max Planck Society
19 United States Lita Annenberg Hazen Genome Center Cold Spring Harbor Laboratory
20 Germany GBF/German Research Centre for Biotechnology Reorganized and renamed to Helmholtz Center for Infection Research

State of completion

The project was not able to sequence all the DNA found in human cells. It sequenced only euchromatic regions of the genome, which make up 92% of the human genome. The other regions, called heterochromatic, are found in centromeres and telomeres, and were not sequenced under the project.[26]

The Human Genome Project (HGP) was declared complete in April 2003. An initial rough draft of the human genome was available in June 2000 and by February 2001 a working draft had been completed and published followed by the final sequencing mapping of the human genome on April 14, 2003. Although this was reported to cover 99% of the euchromatic human genome with 99.99% accuracy, a major quality assessment of the human genome sequence was published on May 27, 2004 indicating over 92% of sampling exceeded 99.99% accuracy which was within the intended goal.[27] Further analyses and papers on the HGP continue to occur.[28]

In March 2009, the Genome Reference Consortium (GRC) released a more accurate version of the human genome, but that still left more than 300 gaps.[29]

In October 2018, the GRC still indicated 514 gaps, most of which are annotated as "stalled" or "under investigation/review", so it seems they will not be resolved any time soon.[30]

Applications and proposed benefits

The sequencing of the human genome holds benefits for many fields, from molecular medicine to human evolution. The Human Genome Project, through its sequencing of the DNA, can help us understand diseases including: genotyping of specific viruses to direct appropriate treatment; identification of mutations linked to different forms of cancer; the design of medication and more accurate prediction of their effects; advancement in forensic applied sciences; biofuels and other energy applications; agriculture, animal husbandry, bioprocessing; risk assessment; bioarcheology, anthropology and evolution. Another proposed benefit is the commercial development of genomics research related to DNA based products, a multibillion-dollar industry.

The sequence of the DNA is stored in databases available to anyone on the Internet. The U.S. National Center for Biotechnology Information (and sister organizations in Europe and Japan) house the gene sequence in a database known as GenBank, along with sequences of known and hypothetical genes and proteins. Other organizations, such as the UCSC Genome Browser at the University of California, Santa Cruz,[31] and Ensembl[32] present additional data and annotation and powerful tools for visualizing and searching it. Computer programs have been developed to analyze the data, because the data itself is difficult to interpret without such programs. Generally speaking, advances in genome sequencing technology have followed Moore's Law, a concept from computer science which states that integrated circuits can increase in complexity at an exponential rate.[33] This means that the speeds at which whole genomes can be sequenced can increase at a similar rate, as was seen during the development of the above-mentioned Human Genome Project.

Techniques and analysis

The process of identifying the boundaries between genes and other features in a raw DNA sequence is called genome annotation and is in the domain of bioinformatics. While expert biologists make the best annotators, their work proceeds slowly, and computer programs are increasingly used to meet the high-throughput demands of genome sequencing projects. Beginning in 2008, a new technology known as RNA-seq was introduced that allowed scientists to directly sequence the messenger RNA in cells. This replaced previous methods of annotation, which relied on inherent properties of the DNA sequence, with direct measurement, which was much more accurate. Today, annotation of the human genome and other genomes relies primarily on deep sequencing of the transcripts in every human tissue using RNA-seq. These experiments have revealed that over 90% of genes contain at least one and usually several alternative splice variants, in which the exons are combined in different ways to produce 2 or more gene products from the same locus.

The genome published by the HGP does not represent the sequence of every individual's genome. It is the combined mosaic of a small number of anonymous donors, all of European origin. The HGP genome is a scaffold for future work in identifying differences among individuals. Subsequent projects sequenced the genomes of multiple distinct ethnic groups, though as of today there is still only one "reference genome."

Findings

Key findings of the draft (2001) and complete (2004) genome sequences include:

  1. There are approximately 22,300[34] protein-coding genes in human beings, the same range as in other mammals.
  2. The human genome has significantly more segmental duplications (nearly identical, repeated sections of DNA) than had been previously suspected.[35][36][37]
  3. At the time when the draft sequence was published fewer than 7% of protein families appeared to be vertebrate specific.[38]

Accomplishment

Wellcome genome bookcase
The first printout of the human genome to be presented as a series of books, displayed at the Wellcome Collection, London

The Human Genome Project was started in 1990 with the goal of sequencing and identifying all three billion chemical units in the human genetic instruction set, finding the genetic roots of disease and then developing treatments. It is considered a megaproject because the human genome has approximately 3.3 billion base pairs. With the sequence in hand, the next step was to identify the genetic variants that increase the risk for common diseases like cancer and diabetes.[16][39]

It was far too expensive at that time to think of sequencing patients’ whole genomes. So the National Institutes of Health embraced the idea for a "shortcut", which was to look just at sites on the genome where many people have a variant DNA unit. The theory behind the shortcut was that, since the major diseases are common, so too would be the genetic variants that caused them. Natural selection keeps the human genome free of variants that damage health before children are grown, the theory held, but fails against variants that strike later in life, allowing them to become quite common (In 2002 the National Institutes of Health started a $138 million project called the HapMap to catalog the common variants in European, East Asian and African genomes).[40]

The genome was broken into smaller pieces; approximately 150,000 base pairs in length.[39] These pieces were then ligated into a type of vector known as "bacterial artificial chromosomes", or BACs, which are derived from bacterial chromosomes which have been genetically engineered. The vectors containing the genes can be inserted into bacteria where they are copied by the bacterial DNA replication machinery. Each of these pieces was then sequenced separately as a small "shotgun" project and then assembled. The larger, 150,000 base pairs go together to create chromosomes. This is known as the "hierarchical shotgun" approach, because the genome is first broken into relatively large chunks, which are then mapped to chromosomes before being selected for sequencing.[41][42]

Funding came from the US government through the National Institutes of Health in the United States, and a UK charity organization, the Wellcome Trust, as well as numerous other groups from around the world. The funding supported a number of large sequencing centers including those at Whitehead Institute, the Wellcome Sanger Institute (then called The Sanger Centre) based at the Wellcome Genome Campus, Washington University in St. Louis, and Baylor College of Medicine.[17][43]

The United Nations Educational, Scientific and Cultural Organization (UNESCO) served as an important channel for the involvement of developing countries in the Human Genome Project.[44]

Public versus private approaches

In 1998, a similar, privately funded quest was launched by the American researcher Craig Venter, and his firm Celera Genomics. Venter was a scientist at the NIH during the early 1990s when the project was initiated. The $300,000,000 Celera effort was intended to proceed at a faster pace and at a fraction of the cost of the roughly $3 billion publicly funded project. The Celera approach was able to proceed at a much more rapid rate, and at a lower cost than the public project because it relied upon data made available by the publicly funded project.[45]

Celera used a technique called whole genome shotgun sequencing, employing pairwise end sequencing,[46] which had been used to sequence bacterial genomes of up to six million base pairs in length, but not for anything nearly as large as the three billion base pair human genome.

Celera initially announced that it would seek patent protection on "only 200–300" genes, but later amended this to seeking "intellectual property protection" on "fully-characterized important structures" amounting to 100–300 targets. The firm eventually filed preliminary ("place-holder") patent applications on 6,500 whole or partial genes. Celera also promised to publish their findings in accordance with the terms of the 1996 "Bermuda Statement", by releasing new data annually (the HGP released its new data daily), although, unlike the publicly funded project, they would not permit free redistribution or scientific use of the data. The publicly funded competitors were compelled to release the first draft of the human genome before Celera for this reason. On July 7, 2000, the UCSC Genome Bioinformatics Group released a first working draft on the web. The scientific community downloaded about 500 GB of information from the UCSC genome server in the first 24 hours of free and unrestricted access.[47]

In March 2000, President Clinton announced that the genome sequence could not be patented, and should be made freely available to all researchers. The statement sent Celera's stock plummeting and dragged down the biotechnology-heavy Nasdaq. The biotechnology sector lost about $50 billion in market capitalization in two days.

Although the working draft was announced in June 2000, it was not until February 2001 that Celera and the HGP scientists published details of their drafts. Special issues of Nature (which published the publicly funded project's scientific paper)[48] and Science (which published Celera's paper[49]) described the methods used to produce the draft sequence and offered analysis of the sequence. These drafts covered about 83% of the genome (90% of the euchromatic regions with 150,000 gaps and the order and orientation of many segments not yet established). In February 2001, at the time of the joint publications, press releases announced that the project had been completed by both groups. Improved drafts were announced in 2003 and 2005, filling in to approximately 92% of the sequence currently.

Genome donors

In the IHGSC international public-sector HGP, researchers collected blood (female) or sperm (male) samples from a large number of donors. Only a few of many collected samples were processed as DNA resources. Thus the donor identities were protected so neither donors nor scientists could know whose DNA was sequenced. DNA clones from many different libraries were used in the overall project, with most of those libraries being created by Pieter J. de Jong's. Much of the sequence (>70%) of the reference genome produced by the public HGP came from a single anonymous male donor from Buffalo, New York (code name RP11).[50][51]

HGP scientists used white blood cells from the blood of two male and two female donors (randomly selected from 20 of each) – each donor yielding a separate DNA library. One of these libraries (RP11) was used considerably more than others, due to quality considerations. One minor technical issue is that male samples contain just over half as much DNA from the sex chromosomes (one X chromosome and one Y chromosome) compared to female samples (which contain two X chromosomes). The other 22 chromosomes (the autosomes) are the same for both sexes.

Although the main sequencing phase of the HGP has been completed, studies of DNA variation continued in the International HapMap Project, whose goal was to identify patterns of single-nucleotide polymorphism (SNP) groups (called haplotypes, or “haps”). The DNA samples for the HapMap came from a total of 270 individuals: Yoruba people in Ibadan, Nigeria; Japanese people in Tokyo; Han Chinese in Beijing; and the French Centre d’Etude du Polymorphisme Humain (CEPH) resource, which consisted of residents of the United States having ancestry from Western and Northern Europe.

In the Celera Genomics private-sector project, DNA from five different individuals were used for sequencing. The lead scientist of Celera Genomics at that time, Craig Venter, later acknowledged (in a public letter to the journal Science) that his DNA was one of 21 samples in the pool, five of which were selected for use.[52][53]

In 2007, a team led by Jonathan Rothberg published James Watson's entire genome, unveiling the six-billion-nucleotide genome of a single individual for the first time.[54]

Developments

The work on interpretation and analysis of genome data is still in its initial stages. It is anticipated that detailed knowledge of the human genome will provide new avenues for advances in medicine and biotechnology. Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as Myriad Genetics, started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, hemostasis disorders, cystic fibrosis, liver diseases and many others. Also, the etiologies for cancers, Alzheimer's disease and other areas of clinical interest are considered likely to benefit from genome information and possibly may lead in the long term to significant advances in their management.[40][55]

There are also many tangible benefits for biologists. For example, a researcher investigating a certain form of cancer may have narrowed down their search to a particular gene. By visiting the human genome database on the World Wide Web, this researcher can examine what other scientists have written about this gene, including (potentially) the three-dimensional structure of its product, its function(s), its evolutionary relationships to other human genes, or to genes in mice or yeast or fruit flies, possible detrimental mutations, interactions with other genes, body tissues in which this gene is activated, and diseases associated with this gene or other datatypes. Further, deeper understanding of the disease processes at the level of molecular biology may determine new therapeutic procedures. Given the established importance of DNA in molecular biology and its central role in determining the fundamental operation of cellular processes, it is likely that expanded knowledge in this area will facilitate medical advances in numerous areas of clinical interest that may not have been possible without them.[56]

The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of evolution. In many cases, evolutionary questions can now be framed in terms of molecular biology; indeed, many major evolutionary milestones (the emergence of the ribosome and organelles, the development of embryos with body plans, the vertebrate immune system) can be related to the molecular level. Many questions about the similarities and differences between humans and our closest relatives (the primates, and indeed the other mammals) are expected to be illuminated by the data in this project.[40][57]

The project inspired and paved the way for genomic work in other fields, such as agriculture. For example, by studying the genetic composition of Tritium aestivum, the world's most commonly used bread wheat, great insight has been gained into the ways that domestication has impacted the evolution of the plant.[58] Which loci are most susceptible to manipulation, and how does this play out in evolutionary terms? Genetic sequencing has allowed these questions to be addressed for the first time, as specific loci can be compared in wild and domesticated strains of the plant. This will allow for advances in genetic modification in the future which could yield healthier and disease-resistant wheat crops, etc.

Ethical, legal and social issues

At the onset of the Human Genome Project several ethical, legal, and social concerns were raised in regards to how increased knowledge of the human genome could be used to discriminate against people. One of the main concerns of most individuals was the fear that both employers and health insurance companies would refuse to hire individuals or refuse to provide insurance to people because of a health concern indicated by someone's genes.[59] In 1996 the United States passed the Health Insurance Portability and Accountability Act (HIPAA) which protects against the unauthorized and non-consensual release of individually identifiable health information to any entity not actively engaged in the provision of healthcare services to a patient.[60] Other nations passed no such protections.

Along with identifying all of the approximately 20,000–25,000 genes in the human genome, the Human Genome Project also sought to address the ethical, legal, and social issues that were created by the onset of the project. For that the Ethical, Legal, and Social Implications (ELSI) program was founded in 1990. Five percent of the annual budget was allocated to address the ELSI arising from the project.[17][61] This budget started at approximately $1.57 million in the year 1990, but increased to approximately $18 million in the year 2014.[62]

Whilst the project may offer significant benefits to medicine and scientific research, some authors have emphasized the need to address the potential social consequences of mapping the human genome. "Molecularising disease and their possible cure will have a profound impact on what patients expect from medical help and the new generation of doctors' perception of illness."[63]

See also

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Further reading

  • McElheny, Victor K. (2010). Drawing the Map of Life: Inside the Human Genome Project. Basic Books. ISBN 978-0-465-03260-0. 361 pages. Examines the intellectual origins, history, and motivations of the project to map the human genome; draws on interviews with key figures.
  • Collins, F. (2006). The Language of God: A Scientist Presents Evidence for Belief. Free Press. ISBN 978-0-7432-8639-8. OCLC 65978711.
  • Venter, J. Craig (October 18, 2007). A Life Decoded: My Genome: My Life. New York, New York: Viking Adult. ISBN 978-0-670-06358-1. OCLC 165048736.
  • Cook-Deegan, Robert (1994). The Gene Wars: Science, Politics, and the Human Genome. New York: W W Norton.

External links

Works by archive
BioPerl

BioPerl is a collection of Perl modules that facilitate the development of Perl scripts for bioinformatics applications. It has played an integral role in the Human Genome Project.

Craig Venter

John Craig Venter (born October 14, 1946) is an American biotechnologist, biochemist, geneticist, and businessman. He is known for leading the first draft sequence of the human genome and assembled the first team to transfect a cell with a synthetic chromosome. Venter founded Celera Genomics, The Institute for Genomic Research (TIGR) and the J. Craig Venter Institute (JCVI), where he currently serves as CEO. He was the co-founder of Human Longevity Inc. and Synthetic Genomics. He was listed on Time magazine's 2007 and 2008 Time 100 list of the most influential people in the world. In 2010, the British magazine New Statesman listed Craig Venter at 14th in the list of "The World's 50 Most Influential Figures 2010". He is a member of the USA Science and Engineering Festival's Advisory Board.

David Haussler

David Haussler (born 1953) is an American bioinformatician known for his work leading the team that assembled the first human genome sequence in the race to complete the Human Genome Project and subsequently for comparative genome analysis that deepens understanding the molecular function and evolution of the genome. He is a Howard Hughes Medical Institute Investigator, professor of biomolecular engineering and director of the Center for Biomolecular Science and Engineering at the University of California, Santa Cruz, director of the California Institute for Quantitative Biosciences (QB3) on the UC Santa Cruz campus, and a consulting professor at the Stanford University School of Medicine and the UC San Francisco Biopharmaceutical Sciences Department.

Ensembl genome database project

Ensembl genome database project is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent completion of the Human Genome Project. Ensembl aims to provide a centralized resource for geneticists, molecular biologists and other researchers studying the genomes of our own species and other vertebrates and model organisms. Ensembl is one of several well known genome browsers for the retrieval of genomic information.

Similar databases and browsers are found at NCBI and the University of California, Santa Cruz (UCSC).

Eric Lander

Eric Steven Lander (born February 3, 1957), a mathematician and geneticist, is a Professor of Biology at the Massachusetts Institute of Technology (MIT), former member of the Whitehead Institute, and founding director of the Broad Institute of MIT and Harvard. He was co-chair of U.S. President Barack Obama's Council of Advisors on Science and Technology.

Eugene Myers

Eugene Wimberly "Gene" Myers, Jr. (born December 31, 1953) is an American computer scientist and bioinformatician, who is best known for contributing to the early development of the NCBI's BLAST tool for sequence analysis.

Francis Collins

Francis Sellers Collins (born April 14, 1950) is an American physician-geneticist who discovered the genes associated with a number of diseases and led the Human Genome Project. He is director of the National Institutes of Health (NIH) in Bethesda, Maryland, United States.

Before being appointed director of the NIH, Collins led the Human Genome Project and other genomics research initiatives as director of the National Human Genome Research Institute (NHGRI), one of the 27 institutes and centers at NIH. Before joining NHGRI, he earned a reputation as a gene hunter at the University of Michigan. He has been elected to the Institute of Medicine and the National Academy of Sciences, and has received the Presidential Medal of Freedom and the National Medal of Science.

Collins also has written a number of books on science, medicine, and religion, including the New York Times bestseller, The Language of God: A Scientist Presents Evidence for Belief. After leaving the directorship of NHGRI and before becoming director of the NIH, he founded and served as president of The BioLogos Foundation, which promotes discourse on the relationship between science and religion and advocates the perspective that belief in Christianity can be reconciled with acceptance of evolution and science, especially through the advancement of evolutionary creation. In 2009, Pope Benedict XVI appointed Collins to the Pontifical Academy of Sciences.

Genome Project-Write

The Genome Project - Write (also known as GP-Write) includes sub-projects like Human Genome Project-Write (HGP-Write), formally announced on 2 Jun 2016, is an extension of Genome Projects (aimed at reading genomes since 1984), now to include development of technologies for synthesis and testing of many genomes of microbes, plants and animals. This leverages two decades of work on Synthetic Biology and Artificial gene synthesis.

The newly created GP-Write project will be managed by the Center of Excellence for Engineering Biology, a new nonprofit organization. The researchers expect that the ability to synthesize large portions of many genomes would result in many scientific and medical advances.

Hamilton O. Smith

Hamilton Othanel Smith (born August 23, 1931) is an American microbiologist and Nobel laureate.Smith was born on August 23, 1931, and graduated from University Laboratory High School of Urbana, Illinois. He attended the University of Illinois at Urbana-Champaign, but in 1950 transferred to the University of California, Berkeley, where he earned his B.A. in Mathematics in 1952 [1]. He received his medical degree from Johns Hopkins University in 1956. In 1975, he was awarded a Guggenheim Fellowship he spent at the University of Zurich.

In 1970, Smith and Kent W. Wilcox discovered the first type II restriction enzyme, that is now called as HindII. Smith went on to discover DNA methylases that constitute the other half of the bacterial host restriction and modification systems, as hypothesized by Werner Arber of Switzerland.He was awarded the Nobel Prize in Physiology or Medicine in 1978 for discovering type II restriction enzymes with Werner Arber and Daniel Nathans as co-recipients.

He later became a leading figure in the nascent field of genomics, when in 1995 he and a team at The Institute for Genomic Research sequenced the first bacterial genome, that of Haemophilus influenzae. H. influenza was the same organism in which Smith had discovered restriction enzymes in the late 1960s. He subsequently played a key role in the sequencing of many of the early genomes at The Institute for Genomic Research, and in the assembly of the human genome at Celera Genomics, which he joined when it was founded in 1998.

More recently, he has directed a team at the J. Craig Venter Institute that works towards creating a partially synthetic bacterium, Mycoplasma laboratorium. In 2003 the same group synthetically assembled the genome of a virus, Phi X 174 bacteriophage. Currently, Smith is scientific director of privately held Synthetic Genomics, which was founded in 2005 by Craig Venter to continue this work. Currently, Synthetic Genomics is working to produce biofuels on an industrial-scale using recombinant algae and other microorganisms.

Human Genome Organisation

The Human Genome Organisation (HUGO) is an organization involved in the Human Genome Project, a project about mapping the human genome. HUGO was established in 1989 as an international organization, primarily to foster collaboration between genome scientists around the world. The HUGO Gene Nomenclature Committee (HGNC), sometimes referred to as "HUGO", is one of HUGO's most active committees and aims to assign a unique gene name and symbol to each human gene.

Jim Kent

William James Kent (born February 10, 1960) is an American research scientist and computer programmer. He has been a contributor to genome database projects and the 2003 winner of the Benjamin Franklin Award.

John Sulston

Sir John Edward Sulston (27 March 1942 – 6 March 2018) was a British biologist and academic who won the Nobel Prize in Physiology or Medicine for his work on the cell lineage and genome of the worm Caenorhabditis elegans in 2002 with his colleagues Sydney Brenner and Robert Horvitz. He was a leader in human genome research and Chair of the Institute for Science, Ethics and Innovation at the University of Manchester.

Sulston was in favour of science in the public interest, such as free public access of scientific information and against the patenting of genes and the privatisation of genetic technologies.

Leroy Hood

Leroy "Lee" Edward Hood (born October 10, 1938) is an American biologist who has served on the faculties at the California Institute of Technology (Caltech) and the University of Washington.

Hood has developed ground-breaking scientific instruments which made possible major advances in the biological sciences and the medical sciences. These include

the first gas phase protein sequencer (1982), for determining the amino acids that make up a given protein;

a DNA synthesizer (1983), to synthesize short sections of DNA;

a peptide synthesizer (1984), to combine amino acids into longer peptides and short proteins;

the first automated DNA sequencer (1986), to identify the order of nucleotides in DNA;

ink-jet oligonucleotide technology for synthesizing DNA and

nanostring technology for analyzing single molecules of DNA and RNA.The protein sequencer, DNA synthesizer, peptide synthesizer, and DNA sequencer were commercialized through Applied Biosystems, Inc. and the ink-jet technology was commercialized through Agilent Technologies.

The automated DNA sequencer was an enabling technology for the Human Genome Project. The peptide synthesizer was used in the synthesis of the HIV protease by Stephen Kent and others, and the development of a protease inhibitor for AIDS treatment.Hood established the first cross-disciplinary biology department, the Department of Molecular Biotechnology (MBT), at the University of Washington in 1992, and co-founded the Institute for Systems Biology in 2000. Hood is credited with introducing the term "systems biology", and advocates for "P4 medicine", medicine that is "predictive, personalized, preventive, and participatory." Scientific American counted him among the 10 most influential people in the field of biotechnology in 2015.

Los Alamos Science

Los Alamos Science, was the Los Alamos National Laboratory's flagship publication in the years 1980 to 2005. Its main purpose was to present the Laboratory's research and its significance to national security to the scientific community, and US government policymakers.Special issues appeared on subjects such as Particle physics, Stan Ulam, and the Human Genome Project.

"Pedagogical articles" were intended to explain difficult concepts in one field to scientists and students in other fields.

Molecular genetics

Molecular genetics is the field of biology that studies the structure and function of genes at a molecular level and thus employs methods of both molecular biology and genetics. The study of chromosomes and gene expression of an organism can give insight into heredity, genetic variation, and mutations. This is useful in the study of developmental biology and in understanding and treating genetic diseases.

Victor A. McKusick

Victor Almon McKusick (October 21, 1921 – July 22, 2008) was an American internist and medical geneticist, and Professor of Medicine at the Johns Hopkins Hospital, Baltimore. He was a proponent of the mapping of the human genome due to its use for studying congenital diseases. He is well known for his studies of the Amish and, what he called, "little people". He was the original author and, until his death, remained chief editor of Mendelian Inheritance in Man (MIM) and its online counterpart Online Mendelian Inheritance in Man (OMIM). He is widely known as the "father of medical genetics".

Virginia Cornish

Virginia Wood Cornish is the Helena Rubinstein Professor of Chemistry at Columbia University.

Wellcome Sanger Institute

The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.It is located on the Wellcome Genome Campus by the village of Hinxton, outside Cambridge. It shares this location with the European Bioinformatics Institute. It was established in 1992 and named after double Nobel Laureate, Frederick Sanger. It was conceived as a large scale DNA sequencing centre to participate in the Human Genome Project, and went on to make the largest single contribution to the gold standard sequence of the human genome. From its inception the Institute established and has maintained a policy of data sharing, and does much of its research in collaboration.

Since 2000, the Institute expanded its mission to understand "the role of genetics in health and disease". The Institute now employs around 900 people and engages in four main areas of research: Human genetics, pathogen genetics, mouse and zebrafish genetics and bioinformatics.

Yeast artificial chromosome

Yeast artificial chromosomes (YACs) are genetically engineered chromosomes derived from the DNA of the yeast, Saccharomyces cerevisiae, which is then ligated into a bacterial plasmid. By inserting large fragments of DNA, from 100–1000 kb, the inserted sequences can be cloned and physically mapped using a process called chromosome walking. This is the process that was initially used for the Human Genome Project, however due to stability issues, YACs were abandoned for the use of Bacterial artificial chromosomes (BAC). Beginning with the initial research of the Rankin et al., Strul et al., and Hsaio et al., the inherently fragile chromosome was stabilized by discovering the necessary autonomously replicating sequence (ARS); a refined YAC utilizing this data was described in 1983 by Murray et al. The primary components of a YAC are the ARS, centromere, and telomeres from S. cerevisiae. Additionally, selectable marker genes, such as antibiotic resistance and a visible marker, are utilized to select transformed yeast cells. Without these sequences, the chromosome will not be stable during extracellular replication, and would not be distinguishable from colonies without the vector.

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