View source for Biology:Human Genome Project

{{Short description|Human genome sequencing programme}}
[[File:Logo HGP.jpg|thumb|Logo of the 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 [[Biology:DNA|DNA]], and of identifying, [[Biology:Gene mapping|mapping]] and [[Biology:DNA sequencing|sequencing]] all of the  [[Biology:Gene|gene]]s of the [[Biology:Human genome|human genome]] from both a physical and  a functional standpoint. It started in 1990 and was completed in 2003.<ref>{{cite video |people=Robert Krulwich |date=2003 |url=https://www.pbs.org/wgbh/nova/genome/ |title=Cracking the Code of Life |medium=Television Show |publisher=PBS}}</ref> It remains the world's largest collaborative biological project.<ref>{{cite web|url= http://battelle.org/docs/default-document-library/economic_impact_of_the_human_genome_project.pdf|title= Economic Impact of the Human Genome Project – Battelle|access-date= 1 August 2013|archive-date= 23 December 2012|archive-url= https://web.archive.org/web/20121223040215/http://battelle.org/docs/default-document-library/economic_impact_of_the_human_genome_project.pdf|url-status= dead}}</ref> 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.<ref>{{cite web|url=https://www.genome.gov/11006943/human-genome-project-completion-frequently-asked-questions/|title=Human Genome Project Completion: Frequently Asked Questions|website=National Human Genome Research Institute (NHGRI)}}</ref> Level "complete genome" was achieved in May 2021, with a remaining only 0.3% bases covered by potential issues.<ref>{{Cite web|title=CHM13 T2T v1.1 – Genome – Assembly – NCBI|url=https://www.ncbi.nlm.nih.gov/assembly/GCA_009914755.3|access-date=2021-06-16|website=www.ncbi.nlm.nih.gov}}</ref><ref>{{Cite web|title=Genome List – Genome – NCBI|url=https://www.ncbi.nlm.nih.gov/genome/browse/#!/eukaryotes/51/|access-date=2021-06-16|website=www.ncbi.nlm.nih.gov}}</ref> The final gapless assembly was finished in January 2022.<ref>{{Cite web |title=T2T-CHM13v2.0 – Genome – Assembly – NCBI |url=https://www.ncbi.nlm.nih.gov/assembly/GCF_009914755.1/ |access-date=2022-06-14 |website=www.ncbi.nlm.nih.gov}}</ref>

Funding came from the United States government through the [[Organization:National Institutes of Health|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 [[Company:Celera Corporation|Celera Corporation]], or Celera Genomics, which was formally launched in 1998. Most of the government-sponsored sequencing was performed in twenty universities and research centres in the {{wipe|United States}}, the {{wipe|United Kingdom}}, {{wipe|Japan}}, {{wipe|France}}, {{wipe|Germany}}, and {{wipe|China}},<ref name="genome.gov">{{cite web|title=Human Genome Project Completion: Frequently Asked Questions|url=https://www.genome.gov/human-genome-project/Completion-FAQ|work=genome.gov}}</ref> 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 [[Biology:Haploid|haploid]] [[Biology:Reference genome|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 the 23 human chromosomes pairs (22 pairs of autosomes and a pair of sex chromosomes, known as allosomes). 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 ==
[[File:DNA replication split.svg|thumb]]
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.<ref>{{Cite web|title = Human Genome Project: Sequencing the Human Genome {{!}} Learn Science at Scitable|url = http://www.nature.com/scitable/topicpage/dna-sequencing-technologies-key-to-the-human-828|website = Nature |access-date = 2016-01-25}}</ref><ref>{{Cite web|url=https://web.ornl.gov/sci/techresources/Human_Genome/project/hgp.shtml|title=History of the Human Genome Project|website=web.ornl.gov}}</ref>

In May 1985, Robert Sinsheimer organized a workshop at the [[Organization:University of California, Santa Cruz|University of California, Santa Cruz]], to discuss the feasibility of building a systematic [[Biology:Reference genome|reference genome]] using gene sequencing technologies.<ref>{{cite journal | vauthors = Sinsheimer RL | title = The Santa Cruz Workshop – May 1985 and | journal = Genomics | volume = 5 | issue = 4 | pages = 954–956 | date = November 1989 | pmid = 2591974 | doi = 10.1016/0888-7543(89)90142-0 }}</ref> 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).<ref name="auto">{{cite journal | vauthors = DeLisi C | title = Meetings that changed the world: Santa Fe 1986: Human genome baby-steps | journal = Nature | volume = 455 | issue = 7215 | pages = 876–877 | date = October 2008 | pmid = 18923499 | doi = 10.1038/455876a | bibcode = 2008Natur.455..876D | s2cid = 41637733 | doi-access = free }}</ref> At the same time [[Biography:Renato Dulbecco|Renato Dulbecco]], President of the [[Organization:Salk Institute for Biological Studies|Salk Institute for Biological Studies]], first proposed the concept of [[Biology:Whole genome sequencing|whole genome sequencing]] in an essay in ''Science''.<ref>{{cite journal | vauthors = Dulbecco R | title = A turning point in cancer research: sequencing the human genome | journal = Science | volume = 231 | issue = 4742 | pages = 1055–1056 | date = March 1986 | pmid = 3945817 | doi = 10.1126/science.3945817 | bibcode = 1986Sci...231.1055D }}</ref> 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.<ref>{{Cite book|last=Cook-Deegan|first=Robert M.|title=The Gene Wars: Science, Politics, and the Human Genome|publisher=W.W. Norton|year=1994|location=New York|pages=108}}</ref> [[Biography:James Watson|James Watson]], one of the discoverers of the double helix shape of DNA in the 1950s, 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.<ref>{{Cite web|url=https://clintonwhitehouse5.archives.gov/WH/new/html/Mon_Jan_8_141714_2001.html|title=President Clinton Awards the Presidential Citizens Medals|website=clintonwhitehouse5.archives.gov}}</ref><ref>{{cite web |url=https://commons.wikimedia.org/wiki/File:Plaque_commemorating_the_Human_Genome_Project,_outside_Charles_DeLisi%27s_former_office_at_DOE.png |title = File:Plaque commemorating the Human Genome Project, outside Charles DeLisi's former office at DOE.png – Wikimedia Commons}}</ref><ref>Bevatron's Encyclopedia of Inventions: a compendium of technological leaps, ground break discoveries and scientific breakthroughs that changed the world. The Human Genome Project, Charles DeLisi, pp. 360–362.</ref><ref>Origins of the Human Genome Project: A Political History – Bob Cook-Deegan https://www.youtube.com/watch?v=-opMu4Ld21Q&t=3885s</ref>

The fact that the Santa Fe Workshop was motivated and supported by a federal agency opened a path, albeit a difficult and tortuous one,<ref name="Cook-Deegan">Gene Wars, Op.Cit. p. 102.</ref> 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.<ref>{{cite web|url=https://repository.library.georgetown.edu/handle/10822/556935/discover?filtertype=author&filter_relational_operator=equals&filter=DeLisi%2C+Charles|title=Search|work=georgetown.edu}}</ref> 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,<ref name="Cook-Deegan" /> and ultimately approved by Congress.  Of particular importance in congressional approval was the advocacy of New Mexico Senator Pete Domenici, whom DeLisi had befriended.<ref>{{cite web|url=http://clinton5.nara.gov/WH/new/html/Mon_Jan_8_141714_2001.html|title=President Clinton Awards the Presidential Citizens Medals|work=nara.gov|access-date=2014-08-06|archive-url=https://web.archive.org/web/20120801215612/http://clinton5.nara.gov/WH/new/html/Mon_Jan_8_141714_2001.html|archive-date=2012-08-01|url-status=dead}}</ref>  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.{{cn|date=December 2023}}

Trivelpiece sought and obtained the approval of DeLisi's proposal by Deputy Secretary William Flynn Martin. This chart<ref>{{Cite web |url=http://www.wpainc.com/Archive/Trivelpiece/HGP%20Presenation.jpg |title=Archived copy |access-date=2013-08-19 |archive-url=https://web.archive.org/web/20160303221351/http://www.wpainc.com/Archive/Trivelpiece/HGP%20Presenation.jpg |archive-date=2016-03-03 |url-status=dead }}</ref> 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.{{citation needed|date=October 2023}} This reprogramming was followed by a line item budget of $13 million in the Reagan administration's 1987 budget submission to Congress.<ref name="auto" /> It subsequently passed both Houses. The project was planned to be completed within 15 years.<ref>{{cite journal |last=DeLisi |first=Charles | name-list-style = vanc |title=The Human Genome Project |journal=American Scientist |date=1988 |volume=76 |issue=5 |page=488 |bibcode = 1988AmSci..76..488D }}</ref>
[[File:Proposal to William Martin.jpg|thumb|Proposal to William F. Martin launching the Human Genome Project]]

In 1990, the two major funding agencies, DOE and the [[Organization:National Institutes of Health|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.<ref name=hgmis>{{cite news |url=http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml |title=About the Human Genome Project: What is the Human Genome Project |publisher=The Human Genome Management Information System (HGMIS) |date=2011-07-18 |access-date=2011-09-02 |archive-url=https://web.archive.org/web/20110902062606/http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml |archive-date=2011-09-02 |url-status=dead }}</ref> 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 [[Biography:James Watson|James Watson]] headed the NIH Genome Program. In 1993, Aristides Patrinos succeeded Galas and [[Biography:Francis Collins|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 [[Organization:National Human Genome Research Institute|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.{{cn|date=December 2023}}

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.<ref name=human>{{cite web|author= Human Genome Information Archive|url= http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml|title= About the Human Genome Project|publisher= U.S. Department of Energy & Human Genome Project program|access-date= 1 August 2013|archive-url= https://web.archive.org/web/20110902062606/http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml|archive-date= 2 September 2011|url-status= dead|df= dmy-all}}</ref> In addition to the United States, the international [[Organization:Consortium|consortium]] comprised [[Biology:Geneticist|geneticist]]s in the United Kingdom, France, Australia, China, and myriad other spontaneous relationships.<ref>{{cite web | vauthors = Collins F, Galas D |url=http://www.genome.gov/10001476 |title=A New Five-Year Plan for the United States: Human Genome Program|publisher=National Human Genome Research Institute |date=1993-10-01 | access-date=1 August 2013}}</ref> The project ended up costing less than expected, at about $2.7 billion (equivalent to about $5 billion in 2021).<ref name="genome.gov" /><ref name="Nature">{{cite journal | title = Life on Earth to have its DNA analysed in the name of conservation | journal = Nature | volume = 563 | issue = 7730 | pages = 155–156 | date = November 2018 | pmid = 30401859 | doi = 10.1038/d41586-018-07323-y | bibcode = 2018Natur.563..155. | doi-access =  }}</ref><ref name="PNAS">{{cite journal | vauthors = Lewin HA, Robinson GE, Kress WJ, Baker WJ, Coddington J, Crandall KA, Durbin R, Edwards SV, Forest F, Gilbert MT, Goldstein MM, Grigoriev IV, Hackett KJ, Haussler D, Jarvis ED, Johnson WE, Patrinos A, Richards S, Castilla-Rubio JC, van Sluys MA, Soltis PS, Xu X, Yang H, Zhang G | display-authors = 6 | title = Earth BioGenome Project: Sequencing life for the future of life | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 17 | pages = 4325–4333 | date = April 2018 | pmid = 29686065 | pmc = 5924910 | doi = 10.1073/pnas.1720115115 | bibcode = 2018PNAS..115.4325L | doi-access = free }}</ref>

Two technologies enabled the project: [[Biology:Gene mapping|gene mapping]] and [[Biology:DNA sequencing|DNA sequencing]]. The gene mapping technique of [[Biology:Restriction fragment length polymorphism|restriction fragment length polymorphism]] (RFLP) arose from the search for the location of the breast cancer gene by Mark Skolnick of the University of Utah,<ref>{{Cite book|last=Cook-Deegan|first=Robert M.|title=The Gene Wars: Science, Politics, and the Human Genome|publisher=W.W. Norton|year=1994|location=New York|pages=95–96}}</ref> which began in 1974.<ref>{{Cite book|last1=Bishop|first1=Jerry E.|title=Genome: The Story of the Most Astonishing Scientific Adventure of Our Time--the Attempt to Map All the Genes in the Human Body|last2=Waldholz|first2=Michael|publisher=Simon and Schuster|year=1990|location=New York|pages=54}}</ref> Seeing a linkage marker for the gene, collaboration with David Botstein, Ray White and Ron Davies conceived of a way to construct a [[Biology:Genetic linkage|genetic linkage]] map of the human genome. This enabled scientists to launch the larger human genome effort.<ref>{{Cite book|last1=Bishop|first1=Jerry E.|title=Genome: The Story of the Most Astonishing Scientific Adventure of Our Time – the Attempt to Map All the Genes in the Human Body|last2=Waldholz|first2=Michael|publisher=Simon and Schuster|year=1990|location=New York|pages=201}}</ref>

Because of widespread international cooperation and advances in the field of [[Biology:Genomics|genomics]] (especially in [[Biology:Sequence analysis|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).<ref>{{cite web |url=http://www.ornl.gov/sci/techresources/Human_Genome/project/clinton1.shtml |title=White House Press Release |access-date=2006-07-22}}</ref><ref>{{Cite web|url=https://archive.nytimes.com/www.nytimes.com/library/national/science/062600sci-human-genome.html?amp;sq=francis%252520collins&amp;st=cse&scp=23|title = Scientists Complete Rough Draft of Human Genome}}</ref> This first available rough draft assembly of the genome was completed by the Genome Bioinformatics Group at the [[Organization:University of California, Santa Cruz|University of California, Santa Cruz]], primarily led by then-graduate student [[Biography:Jim Kent|Jim Kent]] and his advisor [[Biography:David Haussler|David Haussler]].<ref>{{Cite journal|last=Gitschier|first=Jane|date=2013-01-31|title=Life, the Universe, and Everything: An Interview with David Haussler|journal=PLOS Genetics|volume=9|issue=1|pages=e1003282|doi=10.1371/journal.pgen.1003282|issn=1553-7390|pmc=3561096|pmid=23382705 |doi-access=free }}</ref> Ongoing sequencing led to the announcement of the essentially complete genome on April 14, 2003, two years earlier than planned.<ref>{{cite news |url=http://news.bbc.co.uk/1/hi/sci/tech/2940601.stm |title=Human genome finally complete |access-date=2006-07-22 |date=2003-04-14 |work=BBC News |first=Ivan |last=Noble | name-list-style = vanc }}</ref><ref>{{cite news|url=https://www.nytimes.com/2013/04/16/science/the-human-genome-project-then-and-now.html|title=Human Genome, Then and Now|last=Kolata|first=Gina | name-list-style = vanc |date=15 April 2013|work=The New York Times|access-date=24 April 2014}}</ref> 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''.<ref>{{cite news |url=https://www.theguardian.com/uklatest/story/0,,-5829253,00.html |title=Guardian Unlimited &#124;UK Latest &#124; Human Genome Project finalised |access-date=2006-07-22 |work=The Guardian |location=London }} {{dead link|date=August 2014}}</ref>

The various institutions, companies, and laboratories which participated in the Human Genome Project are listed below, according to the NIH:<ref name="genome.gov" />

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

== State of completion ==
Notably, the project was not able to sequence all of the DNA found in human cells; rather, the aim was to sequence only ''[[Biology:Euchromatin|euchromatic]]'' regions of the nuclear genome, which make up 92.1% of the human genome. The remaining 7.9% exists in scattered ''[[Biology:Heterochromatin|heterochromatic]]'' regions such as those found in centromeres and telomeres. These regions by their nature are generally more difficult to sequence and so were not included as part of the project's original plans.<ref name=Genoscope>{{cite web|title=The Human Genome Project FAQ|url=http://www.genoscope.cns.fr/spip/The-Human-Genome-Project.html?artsuite=1#FAQ2|website=Genoscope|publisher=Centre National de Séquençage|access-date=12 February 2015|date=2013-10-19|archive-url=https://web.archive.org/web/20150722060952/http://www.genoscope.cns.fr/spip/The-Human-Genome-Project.html?artsuite=1#FAQ2|archive-date=22 July 2015|url-status=dead}}</ref>

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.<ref>{{cite journal | vauthors = Schmutz J, Wheeler J, Grimwood J, Dickson M, Yang J, Caoile C, Bajorek E, Black S, Chan YM, Denys M, Escobar J, Flowers D, Fotopulos D, Garcia C, Gomez M, Gonzales E, Haydu L, Lopez F, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salazar A, Tsai M, Myers RM | display-authors = 6 | title = Quality assessment of the human genome sequence | journal = Nature | volume = 429 | issue = 6990 | pages = 365–368 | date = May 2004 | pmid = 15164052 | doi = 10.1038/nature02390 | doi-access = free | bibcode = 2004Natur.429..365S }}</ref>

In March 2009, the [[Organization:Genome Reference Consortium|Genome Reference Consortium]] (GRC) released a more accurate version of the human genome, but that still left more than 300 gaps,<ref>{{cite journal | vauthors = Dolgin E | title = Human genomics: The genome finishers | journal = Nature | volume = 462 | issue = 7275 | pages = 843–845 | date = December 2009 | pmid = 20016572 | doi = 10.1038/462843a | doi-access =  }}</ref> while 160 such gaps remained in 2015.<ref name="Chaisson">{{cite journal | vauthors = Chaisson MJ, Huddleston J, Dennis MY, Sudmant PH, Malig M, Hormozdiari F, Antonacci F, Surti U, Sandstrom R, Boitano M, Landolin JM, Stamatoyannopoulos JA, Hunkapiller MW, Korlach J, Eichler EE | title = Resolving the complexity of the human genome using single-molecule sequencing | journal = Nature | volume = 517 | issue = 7536 | pages = 608–611 | date = Jan 2015 | pmid = 25383537 | doi = 10.1038/nature13907 | pmc=4317254| bibcode = 2015Natur.517..608C }}</ref>

Though in May 2020, the GRC reported 79 "unresolved" gaps,<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/grc/human/issues?filters=type:gap&asm=GRCh37.p13|title=Human Genome Issues|website=Genome Reference Consortium|access-date=2019-06-29}}</ref> accounting for as much as 5% of the human genome,<ref name=t2t>{{Citation|title=The (near) complete sequence of a human genome|date=2020-10-06|url=https://genomeinformatics.github.io/CHM13v1/}}</ref> months later, the application of new [[Biology:Single-molecule real-time sequencing|long-range sequencing techniques]] and a hydatidiform mole-derived 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 [[Biology:X chromosome|X chromosome]].<ref name=":1">{{Cite journal|last1=Miga|first1=Karen H.|last2=Koren|first2=Sergey|last3=Rhie|first3=Arang|last4=Vollger|first4=Mitchell R.|last5=Gershman|first5=Ariel|last6=Bzikadze|first6=Andrey|last7=Brooks|first7=Shelise|last8=Howe|first8=Edmund|last9=Porubsky|first9=David|last10=Logsdon|first10=Glennis A.|last11=Schneider|first11=Valerie A.|date=September 2020|title=Telomere-to-telomere assembly of a complete human X chromosome|url= |journal=Nature|language=en|volume=585|issue=7823|pages=79–84|doi=10.1038/s41586-020-2547-7|issn=1476-4687|pmc=7484160|pmid=32663838|bibcode=2020Natur.585...79M}}</ref> Similarly, an end-to-end complete sequence of human autosomal [[Biology:Chromosome 8|chromosome 8]] followed several months later.<ref>{{Cite journal |last1=Logsdon |first1=Glennis A. |last2=Vollger |first2=Mitchell R. |last3=Hsieh |first3=PingHsun |last4=Mao |first4=Yafei |last5=Liskovykh |first5=Mikhail A. |last6=Koren |first6=Sergey |last7=Nurk |first7=Sergey |last8=Mercuri |first8=Ludovica |last9=Dishuck |first9=Philip C. |last10=Rhie |first10=Arang |last11=de Lima |first11=Leonardo G. |date=May 2021 |title=The structure, function and evolution of a complete human chromosome 8 |journal=Nature |language=en |volume=593 |issue=7857 |pages=101–107 |doi=10.1038/s41586-021-03420-7 |pmid=33828295 |pmc=8099727 |bibcode=2021Natur.593..101L |issn=1476-4687}}</ref>

In 2021, it was reported that the Telomere-to-Telomere (T2T) consortium had filled in all of the gaps except five in repetitive regions of ribosomal DNA.<ref name="NatureMile">{{cite journal |last1=Wrighton |first1=Katharine |title=Filling in the gaps telomere to telomere |journal=Nature Milestones: Genomic Sequencing |date=February 2021 |page=S21 |url=https://www.nature.com/articles/d42859-020-00117-1}}</ref> Months later, those gaps had also been closed. The full sequence did not contain the [[Biology:Y chromosome|Y chromosome]], which causes the embryo to become male, being absent in the cell line that served as the source for the DNA analyzed. About 0.3% of the full sequence proved difficult to check for quality, and thus might have contained errors,<ref>{{Cite journal|last=Reardon|first=Sara|date=2021-06-04|title=A complete human genome sequence is close: how scientists filled in the gaps|journal=Nature|language=en|volume=594|issue=7862|pages=158–159|doi=10.1038/d41586-021-01506-w|pmid=34089035|bibcode=2021Natur.594..158R|s2cid=235346408|doi-access=free}}</ref> which were being targeted for confirmation.<ref>{{Cite web|title=GitHub – marbl/CHM13-issues: CHM13 human reference genome issue tracking|url=https://github.com/marbl/CHM13-issues|access-date=2021-07-26|website=GitHub|language=en}}</ref> In April 2022, the complete non-Y chromosome sequence was formally published, providing a view of much of the 8% of the genome left out by the HGP.<ref>[https://www.science.org/toc/science/376/6588 Special Issue: Completing the human genome, ''Science'', vol. 376, no. 6588 (1 April 2022)].</ref> In December, 2022, a [[Preprint|preprint]] article claimed that the sequencing of the remaining missing regions of Y chromosome had been performed, thus completing the sequencing of all 24 human chromosomes.<ref>{{cite journal|url=https://www.biorxiv.org/content/10.1101/2022.12.01.518724v1|title=The complete sequence of a human Y chromosome|author=Rhie|display-authors=0|date=2022-12-01|website=bioRxiv|doi=10.1101/2022.12.01.518724 |s2cid=254181409 }}</ref> In August 2023 this preprint was finally published.<ref>{{Cite journal |last1=Rhie |first1=Arang |last2=Nurk |first2=Sergey |last3=Cechova |first3=Monika |last4=Hoyt |first4=Savannah J. |last5=Taylor |first5=Dylan J. |last6=Altemose |first6=Nicolas |last7=Hook |first7=Paul W. |last8=Koren |first8=Sergey |last9=Rautiainen |first9=Mikko |last10=Alexandrov |first10=Ivan A. |last11=Allen |first11=Jamie |last12=Asri |first12=Mobin |last13=Bzikadze |first13=Andrey V. |last14=Chen |first14=Nae-Chyun |last15=Chin |first15=Chen-Shan |date=2023-08-23 |title=The complete sequence of a human Y chromosome |url=https://www.nature.com/articles/s41586-023-06457-y |journal=Nature |volume=621 |issue=7978 |pages=344–354 |language=en |doi=10.1038/s41586-023-06457-y |pmid=37612512 |bibcode=2023Natur.621..344R |s2cid=254181409 |issn=0028-0836}}</ref><ref>{{Cite report |url=https://www.science.org/content/article/most-troublesome-chromosome-gets-new-respect-after-full-sequence |title='Most troublesome chromosome' gets new respect after full sequence |date=2023-08-23 |doi=10.1126/science.adk4669 |language=en}}</ref>

== Applications and proposed benefits ==
The sequencing of the human genome holds benefits for many fields, from [[Medicine:Molecular medicine|molecular medicine]] to [[Biology:Human evolution|human evolution]]. The Human Genome Project, through its sequencing of the DNA, can help researchers understand diseases including: [[Biology:Genotype|genotyping]] of specific [[Biology:Virus|virus]]es to direct appropriate treatment; identification of [[Biology:Mutation|mutation]]s linked to different forms of [[Medicine:Cancer|cancer]]; the design of medication and more accurate prediction of their effects; advancement in forensic applied sciences;  [[Earth:Biofuel|biofuel]]s and other energy applications; [[Earth:Agriculture|agriculture]], animal husbandry, bioprocessing; [[Risk assessment|risk assessment]];  bioarcheology, [[Social:Anthropology|anthropology]] and [[Biology:Evolution|evolution]]. Another proposed benefit is the commercial development of [[Biology:Genomics|genomics]] research related to DNA-based products, a multibillion-dollar industry.{{cn|date=December 2023}}

The sequence of the DNA is stored in [[Database|database]]s available to anyone on the [[Internet]]. The U.S. [[Organization:National Center for Biotechnology Information|National Center for Biotechnology Information]] (and sister organizations in Europe and Japan) house the gene sequence in a database known as [[Biology:GenBank|GenBank]], along with sequences of known and hypothetical genes and proteins. Other organizations, such as the [[Biology:UCSC Genome Browser|UCSC Genome Browser]] at the University of California, Santa Cruz,<ref>{{Cite web|url=http://genome.ucsc.edu/|title=UCSC Genome Browser Home|website=genome.ucsc.edu}}</ref> and Ensembl<ref>{{cite web|url=http://www.ensembl.org|title=Ensembl Genome Browser|work=ensembl.org}}</ref> present additional data and annotation and powerful tools for visualizing and searching it. [[Computer program]]s 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.<ref>{{cite journal | vauthors = Mardis ER | title = The impact of next-generation sequencing technology on genetics | journal = Trends in Genetics | volume = 24 | issue = 3 | pages = 133–141 | date = March 2008 | pmid = 18262675 | pmc = 2680276 | doi = 10.1016/j.tig.2007.12.007 }}</ref> 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 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 [[Biology:Bioinformatics|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.<ref>{{cite journal | vauthors = Liu Y, Gonzàlez-Porta M, Santos S, Brazma A, Marioni JC, Aebersold R, Venkitaraman AR, Wickramasinghe VO | display-authors = 6 | title = Impact of Alternative Splicing on the Human Proteome | language = en | journal = Cell Reports | volume = 20 | issue = 5 | pages = 1229–1241 | date = August 2017 | pmid = 28768205 | pmc = 5554779 | doi = 10.1016/j.celrep.2017.07.025 | url = }}</ref>

 Subsequent projects sequenced the genomes of multiple distinct ethnic groups, though as of 2019 there is still only one "reference genome".<ref>{{cite journal | vauthors = Ballouz S, Dobin A, Gillis JA | title = Is it time to change the reference genome? | journal = Genome Biology | volume = 20 | issue = 1 | pages = 159 | date = August 2019 | pmid = 31399121 | pmc = 6688217 | doi = 10.1186/s13059-019-1774-4 | doi-access = free }}</ref>

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

# There are approximately 22,300<ref>{{cite journal | vauthors = Pertea M, Salzberg SL | title = Between a chicken and a grape: estimating the number of human genes | journal = Genome Biology | volume = 11 | issue = 5 | pages = 206 | date = 2010 | pmid = 20441615 | pmc = 2898077 | doi = 10.1186/gb-2010-11-5-206 | doi-access = free }}</ref> protein-coding genes in human beings, the same range as in other mammals.
# The human genome has significantly more [[Biology:Segmental duplication|segmental duplication]]s (nearly identical, repeated sections of DNA) than had been previously suspected.<ref name="Venter_2004">{{cite journal | vauthors = Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, etal | title = The sequence of the human genome | journal = Science | volume = 291 | issue = 5507 | pages = 1304–1351 | date = February 2001 | pmid = 11181995 | doi = 10.1126/science.1058040 | doi-access =  | bibcode = 2001Sci...291.1304V }}</ref><ref name=ighsc>{{cite journal | vauthors = Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, etal | collaboration = International Human Genome Sequencing Consortium (IHGSC) | title = Finishing the euchromatic sequence of the human genome | journal = Nature | volume = 431 | issue = 7011 | pages = 931–945 | date = October 2004 | pmid = 15496913 | doi = 10.1038/nature03001 | doi-access = free | bibcode = 2004Natur.431..931H }}</ref><ref>{{cite web| url= http://www.genome.gov/12513430 |last=Spencer |first=Geoff | name-list-style = vanc |title= International Human Genome Sequencing Consortium Describes Finished Human Genome Sequence|date=20 December 2004|work=NIH Nes Release |publisher= National Institutes of Health}}</ref>
# At the time when the draft sequence was published, fewer than 7% of [[Biology:Protein family|protein families]] appeared to be vertebrate specific.<ref>{{cite book|page=108|url=https://books.google.com/books?id=yzFFAQAAIAAJ|quote=...brought to light about 1200 protein families. Only 94 protein families, or 7%, appear to be vertebrate specific|title=Design and information in biology: From molecules to systems|isbn=978-1-85312-853-0| vauthors = Bryant JA |date=2007| publisher=WIT Press }}</ref>

=== Accomplishments ===

[[File:Wellcome genome bookcase.png|thumb|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 [[Biology:Base pair|base pair]]s.<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 |doi-access=free }}</ref> 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|megaproject]].

The genome was broken into smaller pieces; approximately 150,000 [[Biology:Base pair|base pair]]s in length.<ref name=wellcome /> These pieces were then ligated into a type of vector known as "[[Biology:Bacterial artificial chromosome|bacterial artificial chromosome]]s", 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 [[Biology:DNA replication|DNA replication]] machinery. Each of these pieces was then sequenced separately as a small "[[Biology:Shotgun sequencing|shotgun]]" project and then assembled. The larger, 150,000 base pairs go together to create chromosomes. This is known as the "[[Biology:Shotgun sequencing#Hierarchical Shotgun sequencing|hierarchical shotgun]]" approach, because the genome is first broken into relatively large chunks, which are then mapped to chromosomes before being selected for sequencing.<ref>{{cite web|url= http://www.ocf.berkeley.edu/~edy/genome/celera.html|title=Celera: A Unique Approach to Genome Sequencing | work= ocf.berkeley.edu|date=2006|publisher=Biocomputing | access-date=1 August 2013}}</ref><ref>{{cite web|author =Davidson College |url= http://www.bio.davidson.edu/courses/genomics/method/shotgun.html|title= Sequencing Whole Genomes: Hierarchical Shotgun Sequencing v. Shotgun Sequencing | work=bio.davidson.edu |date=2002|publisher=Department of Biology, Davidson College | access-date=1 August 2013}}</ref>

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 [[Organization:Whitehead Institute|Whitehead Institute]], the Wellcome Sanger Institute (then called The Sanger Centre) based at the [[Biology:Wellcome Genome Campus|Wellcome Genome Campus]], [[Organization:Washington University in St. Louis|Washington University in St. Louis]], and Baylor College of Medicine.<ref name=human /><ref>{{cite web|author = Human Genome Project Information Archive|url=http://web.ornl.gov/sci/techresources/Human_Genome/research/centers.shtml |title= U.S. & International HGP Research Sites| date=2013|publisher= U.S. Department of Energy & Human Genome Project | access-date=1 August 2013}}</ref>

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.<ref>{{cite journal|last1=Vizzini|first1=Casimiro | name-list-style = vanc |title=The Human Variome Project: Global Coordination in Data Sharing|journal=Science & Diplomacy|date=March 19, 2015|volume=4|issue=1|url=http://www.sciencediplomacy.org/article/2015/human-variome-project}}</ref>

== Public vis-à-vis private approaches ==
In 1998, a similar, privately funded quest was launched by the American researcher [[Biography:Craig Venter|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 million 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. While the Celera project focused its efforts on production sequencing and assembly of the human genome, the public HGP also funded mapping and sequencing of the [[Biology:Caenorhabditis elegans|worm]], [[Biology:Drosophila melanogaster|fly]], and [[Biology:Saccharomyces cerevisiae|yeast]] genomes, funding of databases, development of new technologies, supporting bioinformatics and ethics programs, as well as polishing and assessment of the genome assembly.<ref>{{cite book|last1=Sulston|first1=John|last2=Ferry|first2=Georgina|date=2002|title=The Common Thread: A Story of Science, Politics, Ethics and the Human Genome|location=London|publisher=Bantam Press|page=160|isbn=0593-048016}}</ref> Both the Celera and public approaches spent roughly $250 million on the production sequencing effort.<ref>{{Cite news|last=Wade|first=Nicholas|date=March 23, 1999|title=Who'll Sequence Human Genome First? It's Up to Phred|url=https://www.nytimes.com/1999/03/23/science/who-ll-sequence-human-genome-first-it-s-up-to-phred.html|newspaper={{wipe|New York Times}}}}</ref> For sequence assembly, Celera made use of publicly available maps at [[Biology:GenBank|GenBank]], which Celera was capable of generating, but the availability of which was "beneficial" to the privately-funded project.<ref name="Venter_2004" />

Celera used a technique called whole genome shotgun sequencing, employing [[Biology:Shotgun sequencing#Whole genome shotgun sequencing|pairwise end sequencing]],<ref>{{cite journal | vauthors = Roach JC, Boysen C, Wang K, Hood L | title = Pairwise end sequencing: a unified approach to genomic mapping and sequencing | journal = Genomics | volume = 26 | issue = 2 | pages = 345–353 | date = March 1995 | pmid = 7601461 | doi = 10.1016/0888-7543(95)80219-C }}</ref> 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 "[[Biology:Bermuda Principles|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&nbsp;GB of information from the UCSC genome server in the first 24 hours of free and unrestricted access.<ref>{{cite web |author=Center for Biomolecular Science & Engineering|url=http://www.cbse.ucsc.edu/research/hgp_race |title=The Human Genome Project Race |publisher=Center for Biomolecular Science and Engineering |access-date=1 August 2013}}</ref>

In March 2000, President Clinton, along with Prime Minister Tony Blair in a dual statement, urged that all researchers who wished to research the sequence should have "unencumbered access" to the genome sequence.<ref>{{Cite news|last=Gillis|first=Justin|date=March 15, 2000|title=Clinton, Blair Urge Open Access to Gene Data|url=https://www.washingtonpost.com/wp-srv/WPcap/2000-03/15/036r-031500-idx.html|newspaper=Washington Post}}</ref>  The statement sent Celera's stock plummeting and dragged down the [[Engineering:Biotechnology|biotechnology]]-heavy [[Finance:Nasdaq|Nasdaq]]. The biotechnology sector lost about $50 billion in [[Social:Market capitalization|market capitalization]] in two days.{{cn|date=December 2023}}

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 [[Academic publishing|scientific paper]])<ref name="Venter_2004" /> 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.{{cn|date=December 2023}}

== Genome donors ==
In the International Human Genome Sequencing Consortium (IHGSC) [[Social:Public sector|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 taken from many different libraries were used in the overall project, with most of those libraries being created by Pieter J. de Jong.  Much of the sequence (>70%) of the [[Biology:Reference genome|reference genome]] produced by the public HGP came from a single anonymous male donor from Buffalo, New York, ([[Social:Code name|code name]] RP11; the "RP" refers to Roswell Park Comprehensive Cancer Center).<ref>{{cite journal | vauthors = Osoegawa K, Mammoser AG, Wu C, Frengen E, Zeng C, Catanese JJ, de Jong PJ | title = A bacterial artificial chromosome library for sequencing the complete human genome | journal = Genome Research | volume = 11 | issue = 3 | pages = 483–496 | date = March 2001 | pmid = 11230172 | pmc = 311044 | doi = 10.1101/gr.169601 }}</ref><ref>{{cite journal | vauthors = Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA, Pertz LM, Haugen E, Hayden H, Albertson D, Pinkel D, Olson MV, Eichler EE | display-authors = 6 | title = Fine-scale structural variation of the human genome | journal = Nature Genetics | volume = 37 | issue = 7 | pages = 727–732 | date = July 2005 | pmid = 15895083 | doi = 10.1038/ng1562 | s2cid = 14162962 }}</ref>

[[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[Biology:Karyotype|karyogram]] of a human, showing an overview of the human genome, with 22 homologous chromosomes, both the female (XX) and male (XY) versions of the sex chromosome (bottom right), as well as the mitochondrial genome (to scale at bottom left). The blue scale to the left of each chromosome pair (and the mitochondrial genome) shows its length in terms of millions of DNA base pairs.{{further|Karyotype}}]]
HGP scientists used [[Biology:White blood cell|white blood cell]]s 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, because of quality considerations.  One minor technical issue is that male samples contain just over half as much DNA from the sex chromosomes (one [[Biology:X chromosome|X chromosome]] and one [[Biology:Y chromosome|Y chromosome]]) compared to female samples (which contain two [[Biology:X chromosome|X chromosome]]s). 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 [[Biology:Single-nucleotide polymorphism|single-nucleotide polymorphism]] (SNP) groups (called [[Biology:Haplotype|haplotype]]s, or "haps"). The DNA samples for the HapMap came from a total of 270 individuals; Yoruba people in Ibadan, Nigeria; Japanese people in [[Place:Tokyo|Tokyo]]; Han Chinese in [[Place:Beijing|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 [[Place:Northern Europe|Northern Europe]].

In the Celera Genomics [[Finance:Private sector|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.<ref>{{cite journal | vauthors = Kennedy D | title = Not wicked, perhaps, but tacky | journal = Science | volume = 297 | issue = 5585 | pages = 1237 | date = August 2002 | pmid = 12193755 | doi = 10.1126/science.297.5585.1237 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Venter JC | title = A part of the human genome sequence | journal = Science | volume = 299 | issue = 5610 | pages = 1183–1184 | date = February 2003 | pmid = 12595674 | doi = 10.1126/science.299.5610.1183 | s2cid = 5188811 }}</ref>

== Developments ==

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.<ref name=hgmis /><ref name=wellcome>{{cite web|author= Wellcome Sanger Institute|url= http://www.sanger.ac.uk/about/history/hgp/|title= The Human Genome Project: a new reality|publisher= Wellcome Trust Sanger Institute, Genome Research Limited|access-date= 1 August 2013|url-status= dead|archive-url= https://web.archive.org/web/20130801231124/http://www.sanger.ac.uk/about/history/hgp/|archive-date= 2013-08-01}}</ref>

It is anticipated that detailed knowledge of the human genome will provide new avenues for advances in [[Medicine:Medicine|medicine]] and [[Engineering:Biotechnology|biotechnology]]. Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as [[Company:Myriad Genetics|Myriad Genetics]], started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including [[Medicine:Breast cancer|breast cancer]], hemostasis disorders, [[Medicine:Cystic fibrosis|cystic fibrosis]], [[Biology:Liver|liver]] diseases and many others. Also, the etiologies for [[Medicine:Cancer|cancer]]s, [[Medicine:Alzheimer's disease|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.<ref name=naid>{{cite journal | vauthors = Naidoo N, Pawitan Y, Soong R, Cooper DN, Ku CS | title = Human genetics and genomics a decade after the release of the draft sequence of the human genome | journal = Human Genomics | volume = 5 | issue = 6 | pages = 577–622 | date = October 2011 | pmid = 22155605 | pmc = 3525251 | doi = 10.1186/1479-7364-5-6-577 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gonzaga-Jauregui C, Lupski JR, Gibbs RA | title = Human genome sequencing in health and disease | journal = Annual Review of Medicine | volume = 63 | issue = 1 | pages = 35–61 | date = 2012 | pmid = 22248320 | pmc = 3656720 | doi = 10.1146/annurev-med-051010-162644 }}</ref>

There are also many tangible benefits for biologists. For example, a researcher investigating a certain form of [[Medicine:Cancer|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 functions, its evolutionary relationships to other human genes, or to genes in mice, 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, a 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 [[Biology:Biological process|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.<ref>{{cite journal | vauthors = Snyder M, Du J, Gerstein M | title = Personal genome sequencing: current approaches and challenges | journal = Genes & Development | volume = 24 | issue = 5 | pages = 423–31 | date = March 2010 | pmid = 20194435 | pmc = 2827837 | doi = 10.1101/gad.1864110 }}</ref>

The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of [[Biology:Evolution|evolution]]. In many cases, evolutionary questions can now be framed in terms of [[Biology:Molecular biology|molecular biology]]; indeed, many major evolutionary milestones (the emergence of the [[Biology:Ribosome|ribosome]] and [[Biology:Organelle|organelle]]s, the development of [[Biology:Embryo|embryo]]s with body plans, the [[Biology:Vertebrate|vertebrate]] [[Biology:Immune system|immune system]]) can be related to the molecular level. Many questions about the similarities and differences between humans and their closest relatives (the [[Biology:Primate|primate]]s, and indeed the other [[Biology:Mammal|mammal]]s) are expected to be illuminated by the data in this project.<ref name=naid /><ref>{{cite journal | vauthors = Lander ES | title = Initial impact of the sequencing of the human genome | journal = Nature | volume = 470 | issue = 7333 | pages = 187–97 | date = February 2011 | pmid = 21307931 | doi = 10.1038/nature09792 | url = https://dspace.mit.edu/bitstream/1721.1/69154/3/ppnature09792%20%28REVISED-CLEAN%29%5b1%5d.pdf | bibcode = 2011Natur.470..187L | hdl = 1721.1/69154 | s2cid = 4344403 | hdl-access = free }}</ref>

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.<ref>{{cite journal| vauthors = Peng JH, Sun D, Nevo E |title=Domestication Evolution, Genetics And Genomics In Wheat|journal=Molecular Breeding|date=2011|volume=28|issue=3|pages=281–301|doi=10.1007/s11032-011-9608-4|s2cid=24886686}}</ref> It is being investigated which loci are most susceptible to manipulation, and how this plays 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 the genetic modification in the future which could yield healthier and disease-resistant wheat crops, among other things.

== Ethical, legal, and social issues ==
At the onset of the Human Genome Project, several ethical, legal, and social concerns were raised in regard to how increased knowledge of the human genome [[Social:Genetic discrimination|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.<ref>{{cite book|last=Greely|first=Henry| name-list-style = vanc |title=The Code of Codes: Scientific and Social Issues in the Human Genome Project|date=1992|publisher=Harvard University Press|location=Cambridge, Massachusetts|isbn=978-0-674-13646-5|pages=[https://archive.org/details/codeofcodesscien00hood/page/264 264–265]|url=https://archive.org/details/codeofcodesscien00hood/page/264}}</ref> In 1996, the United States passed the [[Medicine:Health Insurance Portability and Accountability Act|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.<ref>{{cite web|author = US Department of Health and Human Services|url=https://www.hhs.gov/ocr/privacy/hipaa/understanding/index.html|title=Understanding Health Information Privacy|date=2015-08-26}}</ref>

Along with identifying all of the approximately 20,000–25,000 genes in the human genome (estimated at between 80,000 and 140,000 at the start of the project), the Human Genome Project also sought to address the ethical, legal, and social issues that were created by the onset of the project.<ref name=HGPinsights>{{cite web|author= Human Genome Information Archive|url= http://www.ornl.gov/sci/techresources/Human_Genome/project/journals/insights.shtml|title= Insights Learned from the Human DNA Sequence|publisher= U.S. Department of Energy & Human Genome Project program|access-date= 20 February 2021|archive-url= https://web.archive.org/web/20110903035819/http://www.ornl.gov/sci/techresources/Human_Genome/project/journals/insights.shtml|archive-date= 3 September 2011|url-status= dead|df= dmy-all}}</ref> 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.<ref name=human /><ref>{{cite web| work = Genetics Home Reference | publisher = U.S. National Library of Medicine |url=http://ghr.nlm.nih.gov/handbook/hgp/elsi |title= What were some of the ethical, legal, and social implications addressed by the Human Genome Project? |date=2013|access-date=1 August 2013}}</ref> This budget started at approximately $1.57 million in the year 1990, but increased to approximately $18 million in the year 2014.<ref>{{Cite web|url=https://www.genome.gov/10002329/elsi-research-program-fact-sheet/|title=ELSI Research Program Fact Sheet – National Human Genome Research Institute (NHGRI)|website=www.genome.gov|access-date=2016-09-27}}</ref>

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. Historian of science [[Biography:Hans-Jörg Rheinberger|Hans-Jörg Rheinberger]] wrote that "the prospect of 'molecularizing' diseases and their possible cure will have a profound impact on what patients expect from medical help, and on a new generation of doctors' perception of illness."<ref>{{cite book| vauthors = Rheinberger HJ |title=Living and Working with the New Medical Technologies| url = https://archive.org/details/livingworkingwit00lock | url-access = limited |date=2000|publisher=Cambridge University Press|location=Cambridge|page=[https://archive.org/details/livingworkingwit00lock/page/n29 20]}}</ref>

== See also ==<!-- PLEASE RESPECT ALPHABETICAL ORDER -->
{{col div}}
* {{annotated link|Biology:1000 Genomes Project}}
* {{annotated link|Philosophy:100,000 Genomes Project}}
* {{annotated link|Biology:Chimpanzee genome project}}
* {{annotated link|Biology:ENCODE}}
* {{annotated link|Biology:Physiome}}
* {{annotated link|Organization:HUGO Gene Nomenclature Committee}}
* {{annotated link|Human Brain Project}}
* {{annotated link|Human Connectome Project}}
* {{annotated link|Biology:Cytomics|Human Cytome Project}}
* {{annotated link|Biology:Human Epigenome Project}}
* {{annotated link|Biology:Human Microbiome Project}}
* {{annotated link|Biology:Human proteome project}}
* {{annotated link|Biology:Human Variome Project}}
* {{annotated link|Biology:List of biological databases}}
* {{annotated link|Biology:Neanderthal genome project}}
* {{annotated link|Biology:Genographic Project}}
{{colend}}

== References ==
{{Reflist}}

== Further reading ==
{{refbegin|30em}}
* {{cite book| last = McElheny | first = Victor K. | name-list-style = vanc |title=Drawing the Map of Life: Inside the Human Genome Project|date=2010|publisher=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.
* {{cite book| vauthors = Collins F |date= 2006|title= The Language of God: A Scientist Presents Evidence for Belief| publisher= Free Press| isbn= 978-0-7432-8639-8| oclc= 65978711|title-link= The Language of God: A Scientist Presents Evidence for Belief}}
* {{cite book| vauthors = Venter JC | title = A Life Decoded: My Genome: My Life| date = October 18, 2007| publisher = Viking Adult| location = New York, New York| isbn = 978-0-670-06358-1| oclc = 165048736| url = https://archive.org/details/lifedecodedmygen00vent}}
* {{cite book |first=Robert |last=Cook-Deegan | name-list-style = vanc |title=The Gene Wars: Science, Politics, and the Human Genome |url=https://archive.org/details/genewarssciencep00cook |url-access=registration |year=1994 |publisher=W W Norton |location=New York |isbn=978-0-393-03572-8 }}
* {{cite journal | vauthors = Lone Dog L | title = Whose genes are they? The Human Genome Diversity Project | journal = Journal of Health & Social Policy | volume = 10 | issue = 4 | pages = 51–66 | date = 1999 | pmid = 10538186 | doi = 10.1300/J045v10n04_04 | url = http://www.haworthpress.com/store/ArticleAbstract.asp?sid=DS104W6XGPL58H9EKU06C2L1QSSP41VF&ID=5707 }}
{{refend}}

== External links ==
* [https://www.genome.gov/ National Human Genome Research Institute (NHGRI)]. NHGRI led the National Institutes of Health's contribution to the International Human Genome Project. This project, which had as its primary goal the sequencing of the three billion base pairs that make up the human genome, was successfully completed in April 2003.
* [https://web.ornl.gov/sci/techresources/Human_Genome/publicat/hgn/index.shtml Human Genome News]. Published from 1989 to 2002 by the US Department of Energy, this newsletter was a major communications method for coordination of the Human Genome Project. Complete online archives are available.
* [https://genomicscience.energy.gov/ The HGP information pages] Department of Energy's portal to the international Human Genome Project, Microbial Genome Program, and Genomics:GTL systems biology for energy and environment
* [https://www.yourgenome.org/ yourgenome.org: The Sanger Institute public information pages] has general and detailed primers on DNA, genes, and genomes, the Human Genome Project and science spotlights.
* [https://www.ensembl.org/index.html Ensembl project], an automated annotation system and browser for the human genome
* [https://genome.ucsc.edu/ UCSC genome browser], This site contains the reference sequence and working draft assemblies for a large collection of genomes. It also provides a portal to the ENCODE project.
* [http://www.nature.com/genomics/human/ Nature magazine's human genome gateway], including the HGP's paper on the draft genome sequence
* [https://web.archive.org/web/20100420114125/http://genome.wellcome.ac.uk/ Wellcome Trust Human Genome website] A free resource allowing you to explore the human genome, your health and your future.
* [https://www.ericdigests.org/2003-2/genome.html Learning about the Human Genome. Part 1: Challenge to Science Educators. ERIC Digest.]
* [https://www.ericdigests.org/2003-2/genome2.html Learning about the Human Genome. Part 2: Resources for Science Educators. ERIC Digest.]
* [https://web.archive.org/web/20110916042739/http://prospect.org/cs/articles?article=patenting_life ''Patenting Life'' by  Merrill Goozner]
* [https://web.archive.org/web/20110514175551/http://clinton4.nara.gov/WH/EOP/OSTP/html/00626_4.html Prepared Statement of Craig Venter of Celera] Venter discusses Celera's progress in deciphering the human genome sequence and its relationship to healthcare and to the federally funded Human Genome Project.
* [https://www.pbs.org/wgbh/nova/genome/ Cracking the Code of Life] Companion website to 2-hour NOVA program documenting the race to decode the genome, including the entire program hosted in 16 parts in either [[Software:QuickTime|QuickTime]] or [[Software:RealPlayer|RealPlayer]] format.
* [https://repository.library.georgetown.edu/handle/10822/556935 Bioethics Research Library] Numerous original documents at Georgetown University.
* [http://davidjgalasphd.com/ David J. Galas]
;Works by archive
* {{Gutenberg author | id=856| name=Human Genome Project}}
** [[Project Gutenberg]] hosts e-texts for Human Genome Project, titled ''Human Genome Project, Chromosome Number #'' (# denotes 01–22, X and Y). This information is the raw sequence, released in November 2002; access to entry pages with download links is available through [https://www.gutenberg.org/ebooks/3501 Human Genome Project, Chromosome Number 01] for Chromosome 1 sequentially to [https://www.gutenberg.org/ebooks/3524 Human Genome Project, Y Chromosome] for the Y Chromosome. Note that this sequence might not be considered definitive because of ongoing revisions and refinements. In addition to the chromosome files, there is a [https://www.gutenberg.org/ebooks/11799 supplementary information file] dated March 2004 which contains additional sequence information.
* {{Internet Archive author |sname=Human Genome Project}}
{{Genomics}}
{{Personal genomics}}
{{Great apes}}
{{History of biology}}
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[[Category:Human genome projects| ]]
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{{Sourceattribution|Human Genome Project}}