Original:  When adjusted for inflation, this costs roughly $5 billion (FY 2018). 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 British Prime Minister Tony Blair on June 26, URL 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. 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. The institutions, companies, and laboratories in Human Genome Program are listed below, according to NIH: No. Nation Name Affiliation1The Whitehead Institute/MIT Center for Genome ResearchMassachusetts Institute of Technology2The Wellcome Trust Sanger InstituteWellcome Trust3Washington University School of Medicine Genome Sequencing CenterWashington University in St. Louis4United States DOE Joint Genome InstituteUnited States Department of Energy5Baylor College of Medicine Human Genome Sequencing CenterBaylor College of Medicine6RIKEN Genomic Sciences CenterRiken7Genoscope and CNRS UMR-8030French Alternative Energies and Atomic Energy Commission8GTC Sequencing CenterGenome Therapeutics Corporation, whose sequencing division is acquired by ABI9Department of Genome AnalysisFritz Lipmann Institute, name changed from Institute of Molecular Biotechnology10Beijing Genomics Institute/Human Genome CenterChinese Academy of Sciences11Multimegabase Sequencing CenterInstitute for Systems Biology12Stanford Genome Technology CenterStanford University13Stanford Human Genome Center and Department of GeneticsStanford University School of Medicine14University of Washington Genome CenterUniversity of Washington15Department of Molecular BiologyKeio University School of Medicine16University of Texas Southwestern Medical Center at DallasUniversity of Texas17University of Oklahoma's Advanced Center for Genome TechnologyDept. of Chemistry and Biochemistry, University of Oklahoma18Max Planck Institute for Molecular GeneticsMax Planck Society19Lita Annenberg Hazen Genome CenterCold Spring Harbor Laboratory20GBF/German Research Centre for BiotechnologyReorganized and renamed to Helmholtz Center for Infection Research Additionally, beginning in 2000 and continuing for three years in Russia, the Russian Foundation for Basic Research (RFFI) () provided a grant of about 500 thousand rubles to fund genome mapping of Russians (three groups: Vologda-Vyatka (), Ilmen-Belozersk (), and Valdai ()) by the Laboratory of Human Population Genetics of the Medical Genetics Center of the Russian Academy of Medical Sciences (). Although the top Russian geneticist in 2004 is Sergei Inge-Vechtomov (), the research was headed by Doctor of Biological Sciences Elena Balanovskaya () at the Laboratory of Human Population Genetics in Moscow. Since 2004, Evgeny Ginter is the scientific supervisor of the Medical Genetics Center in Moscow. 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. 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. 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, while 160 such gaps remained in 2015. Though in May 2020, the GRC reported 79 "unresolved" gaps, accounting for as much as 5\% of the human genome, months later the application of new long-range sequencing techniques and a homozygous cell line in which both copies of each chromosome are identical led to the first telomere-to-telomere, truly complete sequence of a human chromosome, the X-chromosome. Work to complete the remaining chromosomes using the same approach is ongoing. In 2021 it was reported that the Telomere-to-Telomere (T2T) consortium had filled in all of the gaps. Thus there came into existence a complete human genome with almost no gaps, but it did not contain 5 last gaps in ribosomal DNA. In May finally last 5 gaps in rDNA were found and published as version 1.1. This sequence does not contain the Y chromosome which causes the embryo to become male, because only duplicated male sperm with X chromosome was present without maternal DNA. About 0.3\% of this sequence proved difficult to check for quality, and thus might contain errors. 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, and Ensembl 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. 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 the 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 the 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: There are approximately 22,300 protein-coding genes in human beings, the same range as in other mammals. The human genome has significantly more segmental duplications (nearly identical, repeated sections of DNA) than had been previously suspected. At the time when the draft sequence was published, fewer than 7\% of protein families appeared to be vertebrate specific. Accomplishments [[Image: Wellcome gbase pairs.<ref>{{cite journal |pmid=30813969|year=2019|last1=Piovesan|first1=A.|last2=Pelleri|first2=M. C.|last3=Antonaros|first3=F.|last4=Strippoli|first4=P.|last5=Caracausi|first5=M.|last6=Vitale|first6=L.|title=On the length, weight and GC content of the human genome|journal=BMC Research Notes|volume=12|issue=1|page=106|doi=10.1186/s13104-019-4137-z|pmc=6391780 300m 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.
Revised:  When adjusted for inflation, this costs roughly $5 billion (FY 2018). 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 British Prime Minister Tony Blair on June 26, URL 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. 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. The institutions, companies, and laboratories in Human Genome Program are listed below, according to NIH: No. Nation Name Affiliation1The Whitehead Institute/MIT Center for Genome ResearchMassachusetts Institute of Technology2The Wellcome Trust Sanger InstituteWellcome Trust3Washington University School of Medicine Genome Sequencing CenterWashington University in St. Louis4United States DOE Joint Genome InstituteUnited States Department of Energy5Baylor College of Medicine Human Genome Sequencing CenterBaylor College of Medicine6RIKEN Genomic Sciences CenterRiken7Genoscope and CNRS UMR-8030French Alternative Energies and Atomic Energy Commission8GTC Sequencing CenterGenome Therapeutics Corporation, whose sequencing division is acquired by ABI9Department of Genome AnalysisFritz Lipmann Institute, name changed from Institute of Molecular Biotechnology10Beijing Genomics Institute/Human Genome CenterChinese Academy of Sciences11Multimegabase Sequencing CenterInstitute for Systems Biology12Stanford Genome Technology CenterStanford University13Stanford Human Genome Center and Department of GeneticsStanford University School of Medicine14University of Washington Genome CenterUniversity of Washington15Department of Molecular BiologyKeio University School of Medicine16University of Texas Southwestern Medical Center at DallasUniversity of Texas17University of Oklahoma's Advanced Center for Genome TechnologyDept. of Chemistry and Biochemistry, University of Oklahoma18Max Planck Institute for Molecular GeneticsMax Planck Society19Lita Annenberg Hazen Genome CenterCold Spring Harbor Laboratory20GBF/German Research Centre for BiotechnologyReorganized and renamed to Helmholtz Center for Infection Research Additionally, beginning in 2000 and continuing for three years in Russia, the Russian Foundation for Basic Research (RFFI) () provided a grant of about 500 thousand rubles to fund genome mapping of Russians (three groups: Vologda-Vyatka (), Ilmen-Belozersk (), and Valdai ()) by the Laboratory of Human Population Genetics of the Medical Genetics Center of the Russian Academy of Medical Sciences (). Although the top Russian geneticist in 2004 is Sergei Inge-Vechtomov (), the research was headed by Doctor of Biological Sciences Elena Balanovskaya () at the Laboratory of Human Population Genetics in Moscow. Since 2004, Evgeny Ginter is the scientific supervisor of the Medical Genetics Center in Moscow. 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. 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. 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, while 160 such gaps remained in 2015. Though in May 2020, the GRC reported 79 "unresolved" gaps, accounting for as much as 5\% of the human genome, months later the application of new long-range sequencing techniques and a homozygous cell line in which both copies of each chromosome are identical led to the first telomere-to-telomere, truly complete sequence of a human chromosome, the X-chromosome. Work to complete the remaining chromosomes using the same approach is ongoing. In 2021 it was reported that the Telomere-to-Telomere (T2T) consortium had filled in all of the gaps. Thus there came into existence a complete human genome with almost no gaps, but it did not contain 5 last gaps in ribosomal DNA. In May finally last 5 gaps in rDNA were found and published as version 1.1. This sequence does not contain the Y chromosome which causes the embryo to become male, because only duplicated male sperm with X chromosome was present without maternal DNA. About 0.3\% of this sequence proved difficult to check for quality, and thus might contain errors. 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, and Ensembl 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. 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 the 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 the 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: There are approximately 22,300 protein-coding genes in human beings, the same range as in other mammals. The human genome has significantly more segmental duplications (nearly identical, repeated sections of DNA) than had been previously suspected. At the time when the draft sequence was published, fewer than 7\% of protein families appeared to be vertebrate specific. Accomplishments The first printout of the human genome to be presented as a series of books, displayed at the Wellcome Collection, London The human genome has approximately 3.1 billion base pairs. The Human Genome Project was started in 1990 with the goal of sequencing and identifying all base pairs in the human genetic instruction set, finding the genetic roots of disease and then developing treatments. It is considered a megaproject. The genome was broken into smaller pieces; approximately 150,000 base pairs in length. 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. 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. 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. 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 $ 300m 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.
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