Human Genome Project

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

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.

Human Genome Project

History

Dna-split.png

The Human Genome Project was a 13-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 at the University of California, Santa Cruz, 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 1979; Ronald W. Davis and colleagues of Stanford University submitted a proposal to NIH that year and it was turned down as being too ambitious.[15][16]

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.[17] 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.[18] In addition to the United States, the international consortium comprised geneticists in the United Kingdom, France, Australia, China and myriad other spontaneous relationships.[19] Adjusted for inflation the project cost roughly $5 billion.[20][21]

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).[22] 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.[23][24] 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.[25]

The institutions, companies and laboratories in Human Genome Program are listed below, according to NIH.[4]

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 92.1% 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]

As of June 2019, the GRC still indicates 89 "unresolved" gaps, most of which are annotated as "stalled" or "under investigation/review".[30]

Other Languages
dansk: HUGO
Bahasa Indonesia: Proyek Genom Manusia
Bahasa Melayu: Projek Genom Manusia
српски / srpski: Projekat ljudskog genoma
srpskohrvatski / српскохрватски: Projekat ljudskog genoma