Human Genome Project
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a physical and a functional standpoint. It started in 1990 and was completed in 2003. It remains the world's largest collaborative biological project. Planning for the project started after it was adopted in 1984 by the US government, and it officially launched in 1990. It was declared complete on April 14, 2003, and included about 92% of the genome. Level "complete genome" was achieved in May 2021, with a remaining only 0.3% bases covered by potential issues. The final gapless assembly was finished in January 2022.
Funding came from the United States government through the National Institutes of Health (NIH) as well as numerous other groups from around the world. A parallel project was conducted outside the 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, working in the International Human Genome Sequencing Consortium (IHGSC).
The Human Genome Project originally aimed to map the complete set of nucleotides contained in a human haploid reference genome, of which there are more than three billion. The "genome" of any given individual is unique; mapping the "human genome" involved sequencing samples collected from a small number of individuals and then assembling the sequenced fragments to get a complete sequence for each of 24 human chromosomes (22 autosomes and 2 sex chromosomes). Therefore, the finished human genome is a mosaic, not representing any one individual. Much of the project's utility comes from the fact that the vast majority of the human genome is the same in all humans.
In May 1985, Robert Sinsheimer organized a workshop at the University of California, Santa Cruz, to discuss the feasibility of building a systematic reference genome using gene sequencing technologies. In March 1986, 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). At the same time Renato Dulbecco, President of the Salk Institute for Biological Studies, first proposed the concept of whole genome sequencing in an essay in Science. The published work, titled "A Turning Point in Cancer Research: Sequencing the Human Genome", was shortened from the original proposal of using the sequence to understand the genetic basis of breast cancer. James Watson, one of the discoverers of the double helix shape of DNA in the 1970s, followed two months later with a workshop held at the Cold Spring Harbor Laboratory. Thus the idea for obtaining a reference sequence had three independent origins: Sinsheimer, Dulbecco and DeLisi. Ultimately it was the actions by DeLisi that launched the project.
The fact that the Santa Fe Workshop was motivated and supported by a federal agency opened a path, albeit a difficult and tortuous one, for converting the idea into public policy in the United States. In a memo to the Assistant Secretary for Energy Research Alvin Trivelpiece, then-Director of the OHER Charles DeLisi outlined a broad plan for the project. 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, and ultimately approved by Congress. Of particular importance in congressional approval was the advocacy of New Mexico Senator Pete Domenici, whom DeLisi had befriended. 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.
Trivelpiece sought and obtained the approval of DeLisi's proposal by Deputy Secretary William Flynn Martin. This chart was used by Trivelpiece in the spring of 1986 to brief Martin and Under Secretary Joseph Salgado regarding his intention to reprogram $4 million to initiate the project with the approval of John S. Herrington. This reprogramming was followed by a line item budget of $16 million in the Reagan administration's 1987 budget submission to Congress. It subsequently passed both Houses. The project was planned to be completed within 15 years.
In 1990, the two major funding agencies, DOE and the National Institutes of Health, developed a memorandum of understanding in order to coordinate plans and set the clock for the initiation of the Project to 1990. At that time, David J. 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 Watson, assuming the role of overall Project Head as Director of the 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 after that.
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. In addition to the United States, the international consortium comprised geneticists in the United Kingdom, France, Australia, China, and myriad other spontaneous relationships. The project ended up costing less than expected, at about $2.7 billion (equivalent to about $5 billion in 2021).
Two technologies enabled the project: gene mapping and DNA sequencing. The gene mapping technique of restriction fragment length polymorphism (RFLP) arose from the search for the location of the breast cancer gene by Dr. Mark Skolnick of the University of Utah, which began in 1974. Seeing a linkage marker for the gene, collaboration with David Botstein, Ray White and Ron Davies conceived of a way to construct a genetic linkage map of the human genome. This enabled scientists to launch the larger human genome effort.
Because of widespread international cooperation and advances in the field of genomics (especially in sequence analysis), as well as parallel advances in computing technology, a 'rough draft' of the genome was finished in 2000 (announced jointly by U.S. President Bill Clinton and British Prime Minister Tony Blair on June 26, 2000). 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 and his advisor David Haussler. Ongoing sequencing led to the announcement of the essentially complete genome on April 14, 2003, two years earlier than planned. In May 2006, another milestone was passed on the way to completion of the project when the sequence of the very last chromosome was published in Nature.
Funding came from the United States government through the National Institutes of Health (NIH) as well as numerous other groups from around the world. A parallel project was conducted outside the 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, working in the International Human Genome Sequencing Consortium (IHGSC).
The Human Genome Project originally aimed to map the complete set of nucleotides contained in a human haploid reference genome, of which there are more than three billion. The "genome" of any given individual is unique; mapping the "human genome" involved sequencing samples collected from a small number of individuals and then assembling the sequenced fragments to get a complete sequence for each of 24 human chromosomes (22 autosomes and 2 sex chromosomes). Therefore, the finished human genome is a mosaic, not representing any one individual. Much of the project's utility comes from the fact that the vast majority of the human genome is the same in all humans.
History
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 13 years.In May 1985, Robert Sinsheimer organized a workshop at the University of California, Santa Cruz, to discuss the feasibility of building a systematic reference genome using gene sequencing technologies. In March 1986, 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). At the same time Renato Dulbecco, President of the Salk Institute for Biological Studies, first proposed the concept of whole genome sequencing in an essay in Science. The published work, titled "A Turning Point in Cancer Research: Sequencing the Human Genome", was shortened from the original proposal of using the sequence to understand the genetic basis of breast cancer. James Watson, one of the discoverers of the double helix shape of DNA in the 1970s, followed two months later with a workshop held at the Cold Spring Harbor Laboratory. Thus the idea for obtaining a reference sequence had three independent origins: Sinsheimer, Dulbecco and DeLisi. Ultimately it was the actions by DeLisi that launched the project.
The fact that the Santa Fe Workshop was motivated and supported by a federal agency opened a path, albeit a difficult and tortuous one, for converting the idea into public policy in the United States. In a memo to the Assistant Secretary for Energy Research Alvin Trivelpiece, then-Director of the OHER Charles DeLisi outlined a broad plan for the project. 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, and ultimately approved by Congress. Of particular importance in congressional approval was the advocacy of New Mexico Senator Pete Domenici, whom DeLisi had befriended. 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.
Trivelpiece sought and obtained the approval of DeLisi's proposal by Deputy Secretary William Flynn Martin. This chart was used by Trivelpiece in the spring of 1986 to brief Martin and Under Secretary Joseph Salgado regarding his intention to reprogram $4 million to initiate the project with the approval of John S. Herrington. This reprogramming was followed by a line item budget of $16 million in the Reagan administration's 1987 budget submission to Congress. It subsequently passed both Houses. The project was planned to be completed within 15 years.
In 1990, the two major funding agencies, DOE and the National Institutes of Health, developed a memorandum of understanding in order to coordinate plans and set the clock for the initiation of the Project to 1990. At that time, David J. 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 Watson, assuming the role of overall Project Head as Director of the 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 after that.
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. In addition to the United States, the international consortium comprised geneticists in the United Kingdom, France, Australia, China, and myriad other spontaneous relationships. The project ended up costing less than expected, at about $2.7 billion (equivalent to about $5 billion in 2021).
Two technologies enabled the project: gene mapping and DNA sequencing. The gene mapping technique of restriction fragment length polymorphism (RFLP) arose from the search for the location of the breast cancer gene by Dr. Mark Skolnick of the University of Utah, which began in 1974. Seeing a linkage marker for the gene, collaboration with David Botstein, Ray White and Ron Davies conceived of a way to construct a genetic linkage map of the human genome. This enabled scientists to launch the larger human genome effort.
Because of widespread international cooperation and advances in the field of genomics (especially in sequence analysis), as well as parallel advances in computing technology, a 'rough draft' of the genome was finished in 2000 (announced jointly by U.S. President Bill Clinton and British Prime Minister Tony Blair on June 26, 2000). 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 and his advisor David Haussler. Ongoing sequencing led to the announcement of the essentially complete genome on April 14, 2003, two years earlier than planned. In May 2006, another milestone was passed on the way to completion of the project when the sequence of the very last chromosome was published in Nature.
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