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The Human Genome Project (HGP) was an international
scientific research The scientific method is an empirical method of acquiring knowledge that has characterized the development of science since at least the 17th century. It involves careful observation, applying rigorous skepticism about what is observed, given t ...

scientific research
project with the goal of determining the
base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA a ...
that make up human
DNA The structure of part of a DNA double helix Deoxyribonucleic acid (; DNA) is a molecule composed of two polynucleotide chains that coil around each other to form a double helix carrying genetic instructions for the development, functioning, g ...
, and of identifying and mapping all of the
gene In biology, a gene (from ''genos'' "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." (Greek) meaning ''generation'' or ''birth'' ) is a basic unit of heredity and a sequence of nucleotides in DNA or R ...
s of the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuc ...
from both a physical and a functional standpoint. It remains the world's largest collaborative biological project. Planning started after the idea was picked up in 1984 by the
US government The federal government of the United States (U.S. federal government) is the national government of the United States, a federal republic in North America, composed of 50 states, a federal district, five major self-governing territories and ...
, the project formally launched in 1990, and was declared complete on April 14, 2003. Funding came from the American government through the
National Institutes of Health The National Institutes of Health (NIH) () is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1880s and is now part of the United States Department of Health an ...
(NIH) as well as numerous other groups from around the world. A parallel project was conducted outside the government by the
Celera Corporation Celera is a subsidiary of Quest Diagnostics which focuses on genetic sequencing and related technologies. It was founded in 1998 as a business unit of Applera, spun off into an independent company in 2008, and finally acquired by Quest Diagnostics ...
, 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
United States The United States of America (USA), commonly known as the United States (U.S. or US), or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major self-governing territories, 326 India ...
, the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain,Usage is mixed. The Guardian' and Telegraph' use Britain as a synonym for the United Kingdom. Some prefer to use Britain as shortha ...
,
Japan , image_flag = Flag of Japan.svg , alt_flag = Centered deep red circle on a white rectangle , image_coat = Imperial Seal of Japan.svg , alt_coat = Golden circle subdivided ...
,
France France (), officially the French Republic (french: link=no, République française), is a country primarily located in Western Europe, consisting of metropolitan France and several overseas regions and territories. The metropolitan area of Fr ...
,
Germany ) , image_map = , map_caption = , map_width = 250px , capital = Berlin , coordinates = , largest_city = capital , languages_type = Official language , languages = German , demonym = German , government_type = Federal parliamentary republi ...
,
Spain , * gl, Reino de España, * oc, Reiaume d'Espanha, , , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = , national_anthem = , image_map = , map_caption = , image_map2 = , ...
, and
China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population of around 1.4 billion. Covering approximately 9.6 million square kilometers (3.7 million m ...
. The Human Genome Project originally aimed to map the
nucleotides Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all l ...

nucleotides
contained in a human
haploid Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Somatic cells, tissues, and individual organisms can be described according to the number of sets ...
reference genome A reference genome (also known as a reference assembly) is a digital nucleic acid sequence database, assembled by scientists as a representative example of the set of genes in one idealized individual organism of a species. As they are assembled ...
(more than three billion). The "genome" of any given individual is unique; mapping the "human genome" involved sequencing a small number of individuals and then assembling to get a complete sequence for each chromosome. Therefore, the finished human genome is a mosaic, not representing any one individual.


Human Genome Project


History

The Human Genome Project was a 13-year-long, publicly funded project initiated in 1990 with the objective of determining the DNA sequence of the entire euchromatic human genome within 15 years. In May 1985, Robert Sinsheimer organized a workshop at the
University of California, Santa Cruz The University of California, Santa Cruz (UC Santa Cruz or UCSC) is a public land-grant research university in Santa Cruz, California. It is one of ten University of California campuses. Located on Monterey Bay, on the edge of the coastal commun ...
, to discuss sequencing the human genome, but for a number of reasons the NIH was uninterested in pursuing the proposal. The following March, the Santa Fe Workshop was organized by
Charles DeLisi Charles Peter DeLisi (born December 9, 1941) is an American biomedical scientist and the Metcalf Professor of Science and Engineering at Boston University. He is noted for seminal contributions to the initiation of the Human Genome Project , for ...
and David Smith of the Department of Energy's Office of Health and Environmental Research (OHER). At the same time
Renato Dulbecco Renato Dulbecco ( , ; February 22, 1914 – February 19, 2012) was an Italian–American virologist who won the 1975 Nobel Prize in Physiology or Medicine for his work on oncoviruses, which are viruses that can cause cancer when they infect animal ...
proposed whole genome sequencing in an essay in Science. James Watson 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,Gene Wars, Op.Cit. p. 102. for converting the idea into public policy in the
United States The United States of America (USA), commonly known as the United States (U.S. or US), or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major self-governing territories, 326 India ...
. In a memo to the Assistant Secretary for Energy Research (Alvin Trivelpiece), Charles DeLisi, who was then Director of the OHER, outlined a broad plan for the project. 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 the Congress. Of particular importance in Congressional approval was the advocacy of New Mexico Senator
Pete Domenici Pietro Vichi "Pete" Domenici (May 7, 1932 – September 13, 2017) was an American attorney and politician from New Mexico. A Republican, Domenici served six terms in the United States Senate from 1973 to 2009; he is the longest-tenured U.S. s ...
, 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.
Alvin Trivelpiece Alvin Trivelpiece, retired Director of Oak Ridge National Laboratory (ORNL), former Executor Officer of American Association for the Advancement of Science (AAAS), and former Director of the Office of Energy Research, U.S. Department of Energy (DOE) ...
sought and obtained the approval of DeLisi's proposal by Deputy Secretary
William Flynn Martin William Flynn Martin (born October 4, 1950) is an American energy economist, educator, and international diplomat. Martin served as Special Assistant to Ronald Reagan for National Security Affairs, Executive Secretary of the United States National ...
. This chart was used in the spring of 1986 by Trivelpiece, then Director of the Office of Energy Research in the Department of Energy, to brief Martin and Under Secretary Joseph Salgado regarding his intention to reprogram $4 million to initiate the project with the approval of . This reprogramming was followed by a line item budget of $16 million in the
Reagan Administration The presidency of Ronald Reagan began at noon EST (17:00 UTC) on January 20, 1981, when Ronald Reagan was inaugurated as the 40th President of the United States, and ended on January 20, 1989. Reagan, a Republican from California, took office f ...
’s 1987 budget submission to Congress. It subsequently passed both Houses. The Project was planned for 15 years. Candidate technologies were already being considered for the proposed undertaking at least as early as 1979; Ronald W. Davis and colleagues of Stanford University submitted a proposal to NIH that year and it was turned down as being too ambitious. In 1990, the two major funding agencies, DOE and NIH, developed a memorandum of understanding in order to coordinate plans and set the clock for the initiation of the Project to 1990. At that time, David Galas was Director of the renamed “Office of Biological and Environmental Research” in the U.S. Department of Energy's Office of Science and
James Watson James Dewey Watson KBE (born April 6, 1928) is an American molecular biologist, geneticist and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick and ...

James Watson
headed the NIH Genome Program. In 1993, Aristides Patrinos succeeded Galas and
Francis Collins Francis Sellers Collins (born April 14, 1950) is an American physician-geneticist who discovered the genes associated with a number of diseases and led the Human Genome Project. He is director of the National Institutes of Health (NIH) in Bethe ...
succeeded
James Watson James Dewey Watson KBE (born April 6, 1928) is an American molecular biologist, geneticist and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick and ...

James Watson
, assuming the role of overall Project Head as Director of the
U.S. National Institutes of Health The National Institutes of Health (NIH) () is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1880s and is now part of the United States Department of Health an ...
(NIH) National Center for Human Genome Research (which would later become the
National Human Genome Research InstituteThe National Human Genome Research Institute (NHGRI) is an institute of the National Institutes of Health, located in Bethesda, Maryland. NHGRI began as the Office of Human Genome Research in The Office of the Director in 1988. This Office transiti ...
). A working draft of the genome was announced in 2000 and the papers describing it were published in February 2001. A more complete draft was published in 2003, and genome "finishing" work continued for more than a decade. The $3 billion project was formally founded in 1990 by the US Department of Energy and the National Institutes of Health, and was expected to take 15 years. In addition to the United States, the international
consortium A consortium (plural: consortia) is an association of two or more individuals, companies, organizations or governments (or any combination of these entities) with the objective of participating in a common activity or pooling their resources for a ...
comprised
geneticist A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. Description A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processes or ...
s in the United kingdoms, France, Australia, China and myriad other spontaneous relationships. Adjusted for inflation the project cost roughly $5 billion. Due to widespread international cooperation and advances in the field of
genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes. In contrast to genetics, which refers t ...
(especially in
sequence analysisIn bioinformatics, sequence analysis is the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution. Methodologies used include sequence alignment ...
), 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 William Jefferson Clinton (''né'' Blythe III; born August 19, 1946) is an American politician and attorney who served as the 42nd president of the United States from 1993 to 2001. Prior to his presidency, he served as governor of Arkansas ...

Bill Clinton
and British
Prime Minister#REDIRECT Prime minister#REDIRECT Prime minister {{R from other capitalisation ...
{{R from other capitalisation ...
Tony Blair Anthony Charles Lynton Blair (born 6 May 1953) is a British politician who served as Prime Minister of the United Kingdom from 1997 to 2007 and Leader of the Labour Party from 1994 to 2007. On his resignation he was appointed Special Envoy o ...

Tony Blair
on June 26, 2000). This first available rough draft
assembly Assembly may refer to: Organisations and meetings * Deliberative assembly, a gathering of members who use parliamentary procedure for making decisions * General assembly, an official meeting of the members of an organization or of their representat ...
of the genome was completed by the Genome Bioinformatics Group at the
University of California, Santa Cruz The University of California, Santa Cruz (UC Santa Cruz or UCSC) is a public land-grant research university in Santa Cruz, California. It is one of ten University of California campuses. Located on Monterey Bay, on the edge of the coastal commun ...
, primarily led by then-graduate student
Jim Kent William James Kent (born February 10, 1960) is an American research scientist and computer programmer. He has been a contributor to genome database projects and the 2003 winner of the Benjamin Franklin Award. Early life Kent was born in Hawaii a ...
. Ongoing
sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succin ...
led to the announcement of the essentially complete
genome In the fields of molecular biology and genetics, a genome is all genetic material of an organism. It consists of DNA (or RNA in RNA viruses). The genome includes both the genes (the coding regions) and the noncoding DNA, as well as mitochond ...
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 Nature, in the broadest sense, is the natural, physical, material world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Al ...
''. The institutions, companies, and laboratories in Human Genome Program are listed below, according to NIH: Additionally, beginning in 2000 and continuing for three years in
Russia Russia (russian: link=no, Россия, , ), or the Russian Federation, is a country spanning Eastern Europe and Northern Asia. It is the largest country in the world, covering and encompassing more than one-eighth of the Earth's inhabited l ...
, the Russian Foundation for Basic Research (RFFI) (russian: Российский фонд фундаментальных исследований (РФФИ)) provided a grant of about 500 thousand rubles to fund genome mapping of Russians (three groups: Vologda-Vyatka (russian: Вологда-Вятка), Ilmen-Belozersk (russian: Ильмень-Белозерск), and Valdai (russian: Валдай)) by the Laboratory of Human Population Genetics of the Medical Genetics Center of the
Russian Academy of Medical SciencesThe USSR Academy of Medical Sciences (russian: Акаде́мия медици́нских нау́к СССР) was the highest scientific and medical organization founded in the Soviet Union founded in 1944. Its successor is the Russian Academy of ...
(russian: лаборатории популяционной генетики человека Медико-генетического центра Российской академии медицинских наук). Although the top Russian geneticist in 2004 is Sergei Inge-Vechtomov (russian: Сергей Инге-Вечтомов), the research was headed by Doctor of Biological Sciences Elena Balanovskaya (russian: Елена Балановская) at the Laboratory of Human Population Genetics in
Moscow Moscow (, ; rus, links=no, Москва, r=Moskva, p=mɐˈskva, a=Москва.ogg) is the capital and largest city of Russia. The city stands on the Moskva River in Central Russia, with a population estimated at 12.4 million residents within the ci ...
. 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 There are many different types of cell in the human body. Cells derived primarily from endoderm Exocrine secretory epithelial cells *Brunner's gland cell in duodenum (enzymes and alkaline mucus) *Insulated goblet cell of respiratory and diges ...
. 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 In this diagram of a duplicated chromosome, (2) identifies the centromere—the region that joins the two sister chromatids, or each half of the chromosome. In prophase of mitosis, specialized regions on centromeres called kinetochores attach chr ...
and
telomeres A telomere ( or , from and ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres in a broad sense, are a widespread genetic ...
, 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 ConsortiumThe Genome Reference Consortium (GRC) is an international collective of academic and research institutes with expertise in genome mapping, sequencing, and informatics, formed to improve the representation of reference genomes. At the time the human ...
(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 The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and X0 sex-dete ...
. Work to complete the remaining chromosomes using the same approach is ongoing.


Applications and proposed benefits

The sequencing of the human genome holds benefits for many fields, from
molecular medicineMolecular medicine is a broad field, where physical, chemical, biological, bioinformatics and medical techniques are used to describe molecular structures and mechanisms, identify fundamental molecular and genetic errors of disease, and to develop mo ...
to
human evolution Human evolution is the evolutionary process that led to the emergence of anatomically modern humans, beginning with the evolutionary history of primates—in particular genus ''Homo''—and leading to the emergence of ''Homo sapiens'' as a distinc ...

human evolution
. The Human Genome Project, through its sequencing of the DNA, can help us understand diseases including:
genotyping Genotyping is the process of determining differences in the genetic make-up (genotype) of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It ...
of specific
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovs ...
es to direct appropriate treatment; identification of
mutation A tulip flower exhibiting a partially yellow petal due to a mutation in its genes In biology, a mutation is an alteration in the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA o ...
s linked to different forms of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleedi ...

cancer
; the design of medication and more accurate prediction of their effects; advancement in
forensic Forensic science, also known as criminalistics, is the application of science to criminal and civil laws, mainly—on the criminal side—during criminal investigation, as governed by the legal standards of admissible evidence and criminal proce ...
applied sciences;
biofuel Biofuel is fuel that is produced through contemporary processes from biomass, rather than by the very slow geological processes involved in the formation of fossil fuels, such as oil. Since biomass technically can be used as a fuel directly (e.g ...
s and other energy applications;
agriculture Agriculture is the science, art and practice of cultivating plants and livestock. Agriculture was the key development in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that enabled peo ...
,
animal husbandry Animal husbandry is the branch of agriculture concerned with animals that are raised for meat, fibre, milk, eggs, or other products. It includes day-to-day care, selective breeding and the raising of livestock. Husbandry has a long history, start ...
,
bioprocessingBioprocess engineering, also biochemical engineering, is a specialization of chemical engineering or Biological engineering, It deals with the design and development of equipment and processes for the manufacturing of products such as agriculture, f ...
;
risk assessment Broadly speaking, a risk assessment is the combined effort of: # identifying and analyzing potential (future) events that may negatively impact individuals, assets, and/or the environment (i.e. hazard analysis); and # making judgments "on the tol ...
; bioarcheology,
anthropology Anthropology is the scientific study of humanity, concerned with human behavior, human biology, cultures, and societies, in both the present and past, including past human species. Social anthropology studies patterns of behaviour, while cultur ...
and
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes that are passed on from parent to offspring during reproduction. Different character ...

evolution
. Another proposed benefit is the commercial development of
genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes. In contrast to genetics, which refers t ...
research related to DNA based products, a multibillion-dollar industry. The sequence of the DNA is stored in
database A database is an organized collection of data, generally stored and accessed electronically from a computer system. Where databases are more complex they are often developed using formal design and modeling techniques. The database management sys ...
s available to anyone on the
Internet The Internet (or internet) is the global system of interconnected computer networks that uses the Internet protocol suite (TCP/IP) to communicate between networks and devices. It is a ''network of networks'' that consists of private, pub ...

Internet
. The U.S.
National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The N ...
(and sister organizations in Europe and Japan) house the gene sequence in a database known as
GenBank The GenBank sequence database is an open access, annotated collection of all publicly available nucleotide sequences and their protein translations. It is produced and maintained by the National Center for Biotechnology Information (NCBI; a part of ...
, along with sequences of known and hypothetical genes and proteins. Other organizations, such as the
UCSC Genome Browser The UCSC Genome Browser is an on-line, and downloadable, genome browser hosted by the University of California, Santa Cruz (UCSC). It is an interactive website offering access to genome sequence data from a variety of vertebrate and invertebrate sp ...
at the University of California, Santa Cruz, and
EnsemblEnsembl genome database project is a scientific project at the European Bioinformatics Institute, which was launched in 1999 in response to the imminent completion of the Human Genome Project. Ensembl aims to provide a centralized resource for geneti ...
present additional data and annotation and powerful tools for visualizing and searching it.
Computer program A computer program is a collection of instructions that can be executed by a computer to perform a specific task. A computer program is usually written by a computer programmer in a programming language. From the program in its human-readable f ...
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#REDIRECT Moore's law#REDIRECT Moore's law {{R from other capitalisation ...
{{R from other capitalisation ...
, 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 DNA annotation or genome annotation is the process of identifying the locations of genes and all of the coding regions in a genome and determining what those genes do. An annotation (irrespective of the context) is a note added by way of explanation ...
and is in the domain of
bioinformatics thumbnail, 220px, Map of the human X chromosome (from the National Center for Biotechnology Information website) Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in partic ...
. 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#redirect RNA-Seq#redirect RNA-Seq {{R from other capitalisation ...
{{R from other capitalisation ...
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 An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...
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 duplication Low copy repeats (LCRs), also known as segmental duplications (SDs), are highly homologous sequence elements within the eukaryotic genome. Repeats They are typically 10–300 kb in length, and bear greater than 95% sequence identity. Though rare in ...
s (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 A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term ''protein family'' should not be co ...
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 sequencing, "shotgun" project and then assembled. The larger, 150,000 base pairs go together to create chromosomes. This is known as the 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. 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, th
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 research funding, publicly funded project. The Celera approach was able to proceed at a much more rapid rate, and at a lower cost, than the public project in part because it used data made available by the publicly funded project. Celera used a technique called whole genome shotgun sequencing#Whole genome shotgun sequencing, whole genome shotgun sequencing, employing Shotgun sequencing#Whole genome shotgun sequencing, pairwise end sequencing, which had been used to sequence bacterial genomes of up to six million base pairs in length, but not for anything nearly as large as the three billion base pair human genome. Celera initially announced that it would seek patent protection on "only 200–300" genes, but later amended this to seeking "intellectual property protection" on "fully-characterized important structures" amounting to 100–300 targets. The firm eventually filed preliminary ("place-holder") patent applications on 6,500 whole or partial genes. Celera also promised to publish their findings in accordance with the terms of the 1996 "Bermuda 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 GB of information from the UCSC genome server in the first 24 hours of free and unrestricted access. In March 2000, Bill Clinton, President Clinton, along with Tony Blair, Prime Minister Tony Blair in a dual statement, urged that the Genome, genome sequence should have "unencumbered access" to all researchers who wished to research the sequence. The statement sent Celera's stock plummeting and dragged down the biotechnology-heavy Nasdaq. The biotechnology sector lost about $50 billion in market capitalization in two days. Although the working draft was announced in June 2000, it was not until February 2001 that Celera and the HGP scientists published details of their drafts. Special issues of ''
Nature Nature, in the broadest sense, is the natural, physical, material world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Al ...
'' (which published the publicly funded project's Academic publishing, scientific paper) 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, News release, press releases announced that the project had been completed by both groups. Improved drafts were announced in 2003 and 2005, filling in to approximately 92% of the sequence currently.


Genome donors

In the IHGSC international Public sector, 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 DNA library, libraries were used in the overall project, with most of those libraries being created by Pieter J. de Jong's. Much of the sequence (>70%) of the
reference genome A reference genome (also known as a reference assembly) is a digital nucleic acid sequence database, assembled by scientists as a representative example of the set of genes in one idealized individual organism of a species. As they are assembled ...
produced by the public HGP came from a single anonymous male donor from Buffalo, New York (code name RP11; the "RP" refers to Roswell Park Comprehensive Cancer Center). HGP scientists used white blood cells from the blood of two male and two female donors (randomly selected from 20 of each) – each donor yielding a separate DNA library. One of these libraries (RP11) was used considerably more than others, due to quality considerations. One minor technical issue is that male samples contain just over half as much DNA from the sex chromosomes (one X chromosome and one Y chromosome) compared to female samples (which contain two X chromosomes). The other 22 chromosomes (the autosomes) are the same for both sexes. Although the main sequencing phase of the HGP has been completed, studies of DNA variation continued in the International HapMap Project, whose goal was to identify patterns of single-nucleotide polymorphism (SNP) groups (called haplotypes, or “haps”). The DNA samples for the HapMap came from a total of 270 individuals; Yoruba people in Ibadan, Nigeria; Japanese people in Tokyo; Han Chinese in Beijing; and the French Center for the Study of Human Polymorphisms, Centre d’Etude du Polymorphisme Humain (CEPH) resource, which consisted of residents of the United States having ancestry from Western and Northern Europe. In the Celera Genomics Private sector, 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 (journal), Science'') that his DNA was one of 21 samples in the pool, five of which were selected for use. In 2007, a team led by Jonathan Rothberg published
James Watson James Dewey Watson KBE (born April 6, 1928) is an American molecular biologist, geneticist and zoologist. In 1953, he co-authored with Francis Crick the academic paper proposing the double helix structure of the DNA molecule. Watson, Crick and ...

James Watson
's entire genome, unveiling the six-billion-nucleotide genome of a single individual for the first time.


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. It is anticipated that detailed knowledge of the human genome will provide new avenues for advances in medicine and biotechnology. Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as Myriad Genetics, started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, blood clotting, hemostasis disorders, cystic fibrosis, liver diseases and many others. Also, the etiology (medicine), etiologies for
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleedi ...

cancer
s, 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. There are also many tangible benefits for biologists. For example, a researcher investigating a certain form of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleedi ...

cancer
may have narrowed down their search to a particular gene. By visiting the human genome database on the World Wide Web, this researcher can examine what other scientists have written about this gene, including (potentially) the three-dimensional structure of its product, its function(s), its evolutionary relationships to other human genes, or to genes in mice or yeast or fruit flies, possible detrimental mutations, interactions with other genes, body tissues in which this gene is activated, and diseases associated with this gene or other datatypes. Further, 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 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. The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes that are passed on from parent to offspring during reproduction. Different character ...

evolution
. In many cases, evolutionary questions can now be framed in terms of molecular biology; indeed, many major evolutionary milestones (the emergence of the ribosome and organelles, the development of embryos with body plans, the vertebrate immune system) can be related to the molecular level. Many questions about the similarities and differences between humans and our closest relatives (the primates, and indeed the other mammals) are expected to be illuminated by the data in this project. The project inspired and paved the way for genomic work in other fields, such as agriculture. For example, by studying the genetic composition of ''Common wheat, 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. 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 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. In 1996 the United States passed the Health Insurance Portability and Accountability Act (HIPAA) which protects against the unauthorized and non-consensual release of individually identifiable health information to any entity not actively engaged in the provision of healthcare services to a patient. Other nations passed no such protections . 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. 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. This budget started at approximately $1.57 million in the year 1990, but increased to approximately $18 million in the year 2014. Whilst the project may offer significant benefits to medicine and scientific research, some authors have emphasized the need to address the potential social consequences of mapping the human genome. "Molecularising disease and their possible cure will have a profound impact on what patients expect from medical help and the new generation of doctors' perception of illness."


See also

* * * * * * * * * * * * * * * * *


References


Further reading

* 361 pages. Examines the intellectual origins, history, and motivations of the project to map the human genome; draws on interviews with key figures. * * * *


External links


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 thousand million base pairs that make up the human genome, was successfully completed in April 2003.
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.
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
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.
Ensembl project
an automated annotation system and browser for the human genome
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.
Nature magazine's human genome gateway
including the HGP's paper on the draft genome sequence
Wellcome Trust Human Genome website
A free resource allowing you to explore the human genome, your health and your future.

* [http://www.ericdigests.org/2003-2/genome2.html Learning about the Human Genome. Part 2: Resources for Science Educators. ERIC Digest.]
''Patenting Life'' by Merrill Goozner


Venter discusses Celera's progress in deciphering the human genome sequence and its relationship to healthcare and to the federally funded Human Genome Project.
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 QuickTime or RealPlayer format.
Bioethics Research Library
Numerous original documents at Georgetown University. ;Works by archive * ** 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 for Chromosome 1 sequentially to https://www.gutenberg.org/ebooks/3524 for the Y Chromosome. Note that this sequence might not be considered definitive due to ongoing revisions and refinements. In addition to the chromosome files, there is
supplementary information file
dated March 2004 which contains additional sequence information. * {{Authority control Human genome projects, Human Genome Project scientists, . Biotechnology Genetics Life sciences industry Wellcome Trust Projects established in 1990 1990 in biotechnology 1990 in biology 1990 in science 1990 establishments in the United States 2003 in biotechnology James Watson