Human Genome Project
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The Human Genome Project (HGP) was an international
scientific research The scientific method is an empirical method for acquiring knowledge that has been referred to while doing science since at least the 17th century. Historically, it was developed through the centuries from the ancient and medieval world. The ...
project with the goal of determining the base pairs that make up human
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
, and of identifying, mapping and sequencing all of the
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s of the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as the DNA within each of the 23 distinct chromosomes in the cell nucleus. A small DNA molecule is found within individual Mitochondrial DNA, mitochondria. These ar ...
from both a physical and a functional standpoint. It started in 1990 and was completed in 2003. It was the world's largest collaborative biological project. Planning for the project began in 1984 by the US government, and it officially launched in 1990. It was declared complete on 14 April 2003, and included about 92% of the genome. Level "complete genome" was achieved in May 2021, with only 0.3% of the bases covered by potential issues. The final gapless assembly was finished in January 2022. Funding came from the US 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 1887 and is part of the United States Department of Health and Human Service ...
(NIH) as well as numerous other groups from around the world. A parallel project was conducted outside the government by the Celera Corporation, or Celera Genomics, which was formally launched in 1998. Most of the government-sponsored sequencing was performed in twenty universities and research centres in the United States, the United Kingdom, Japan, France, Germany, and China, working in the International Human Genome Sequencing Consortium (IHGSC). The Human Genome Project originally aimed to map the complete set of
nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
contained in a human
haploid Ploidy () is the number of complete sets of chromosomes in a cell (biology), cell, and hence the number of possible alleles for Autosome, autosomal and Pseudoautosomal region, pseudoautosomal genes. Here ''sets of chromosomes'' refers to the num ...
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 chromosome 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

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 13 years. The idea that sets of inherited genes predicted the concept of mapping a disease gene to a chromosomal region originated in the work of Ronald A. Fisher, whose work is also credited with later initiating the project. In 1977, Walter Gilbert, Frederick Sanger, and Paul Berg invented these methods of sequencing DNA. 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 university, public Land-grant university, land-grant research university in Santa Cruz, California, United States. It is one of the ten campuses in the University of C ...
, to discuss the feasibility of building a systematic reference genome using gene sequencing technologies. Gilbert wrote the first plan for what he called The Human Genome Institute on the plane ride home from the workshop. In March 1986, the Santa Fe Workshop was organized by Charles DeLisi and David Smith of the Department of Energy's Office of Health and Environmental Research (OHER). At the same time Renato Dulbecco, President of the Salk Institute for Biological Studies, first proposed the concept of
whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing or just genome sequencing, is the process of determining the entirety of the DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's ...
in an essay in ''
Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
''. The published work, titled "A Turning Point in Cancer Research: Sequencing the Human Genome", was shortened from the original proposal of using the sequence to understand the genetic basis of breast cancer.
James Watson James Dewey Watson (born April 6, 1928) is an American molecular biology, molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper in ''Nature (journal), Nature'' proposing the Nucleic acid ...
, 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. 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. In a memo to the Assistant Secretary for Energy Research Alvin Trivelpiece, then-Director of the OHER Charles DeLisi outlined a broad plan for the project. This started a long and complex chain of events that led to the approved reprogramming of funds that enabled the OHER to launch the project in 1986, and to recommend the first line item for the HGP, which was in President Reagan's 1988 budget submission, and ultimately approved by Congress. Of particular importance in congressional approval was the advocacy of New Mexico Senator Pete Domenici, whom DeLisi had befriended. Domenici chaired the Senate Committee on Energy and Natural Resources, as well as the Budget Committee, both of which were key in the DOE budget process. Congress added a comparable amount to the NIH budget, thereby beginning official funding by both agencies. Trivelpiece sought and obtained the approval of DeLisi's proposal from Deputy Secretary William Flynn Martin. This chart was used by Trivelpiece in the spring of 1986 to brief Martin and Under Secretary Joseph Salgado regarding his intention to reprogram $4 million to initiate the project with the approval of John S. Herrington. This reprogramming was followed by a line item budget of $13 million in the
Reagan administration Ronald Reagan's tenure as the 40th president of the United States began with his first inauguration on January 20, 1981, and ended on January 20, 1989. Reagan, a Republican from California, took office following his landslide victory over ...
's 1987 budget submission to Congress. It subsequently passed both Houses. The project was planned to be completed within 15 years. In 1990 the two major funding agencies, DOE and the
National Institutes of Health 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 1887 and is part of the United States Department of Health and Human Service ...
, developed a memorandum of understanding to coordinate plans and set the clock for the initiation of the Project to 1990. At that time, David J. Galas was Director of the renamed "Office of Biological and Environmental Research" in the US Department of Energy's Office of Science and
James Watson James Dewey Watson (born April 6, 1928) is an American molecular biology, molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper in ''Nature (journal), Nature'' proposing the Nucleic acid ...
headed the NIH Genome Program. In 1993, Aristides Patrinos succeeded Galas and Francis Collins succeeded Watson, assuming the role of overall Project Head as Director of the NIH National Center for Human Genome Research (which would later become the
National Human Genome Research Institute The 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 transi ...
). A working draft of the genome was announced in 2000 and the papers describing it were published in February 2001. A more complete draft was published in 2003, and genome "finishing" work continued for more than a decade after that. The $3 billion project was formally founded in 1990 by the US Department of Energy and the National Institutes of Health, and was expected to take 15 years. In addition to the United States, the international
consortium A consortium () 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 achieving a ...
comprised geneticists in the United Kingdom, France, Australia, China, and a myriad of other spontaneous relationships. The project ended up costing less than expected, at about $2.7 billion (equivalent to about $5 billion in 2021). Most of the genome was mapped over a two-year span. Two technologies enabled the project: gene mapping and
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, thymine, cytosine, and guanine. The ...
. The gene mapping technique of 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, which began in 1974. Seeing a linkage marker for the gene, in collaboration with David Botstein, Ray White and Ron Davis conceived of a way to construct a
genetic linkage Genetic linkage is the tendency of Nucleic acid sequence, DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two Genetic marker, genetic markers that are physically near ...
map of the human genome. This enabled scientists to launch the larger human genome effort. Because of widespread international cooperation and advances in the field of
genomics Genomics is an interdisciplinary field of molecular 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 as well as its hierarchical, ...
(especially in
sequence analysis In 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. It can be performed on the entire genome ...
), as well as parallel advances in computing technology, a 'rough draft' of the genome was finished in 2000 (announced jointly by US President
Bill Clinton William Jefferson Clinton (né Blythe III; born August 19, 1946) is an American politician and lawyer who was the 42nd president of the United States from 1993 to 2001. A member of the Democratic Party (United States), Democratic Party, ...
and British Prime Minister
Tony Blair Sir 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 (UK), Leader of the Labour Party from 1994 to 2007. He was Leader ...
on 26 June 2000). This first available rough draft assembly 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 university, public Land-grant university, land-grant research university in Santa Cruz, California, United States. It is one of the ten campuses in the University of C ...
, primarily led by then-graduate student Jim Kent and his advisor David Haussler. Ongoing sequencing led to the announcement of the essentially complete genome on 14 April 2003, two years earlier than planned. In May 2006, another milestone was passed on the way to completion of the project when the sequence of the very last chromosome was published in ''Nature''. The various institutions, companies, and laboratories which participated in the Human Genome Project are listed below, according to the NIH:


State of completion

Notably the project was not able to sequence all of the DNA found in
human cells The list of human cell types provides an enumeration and description of the various specialized cells found within the human body, highlighting their distinct functions, characteristics, and contributions to overall physiological processes. Cell ...
; rather, the aim was to sequence only '' euchromatic'' regions of the nuclear genome, which make up 92.1% of the human genome. The remaining 7.9% exists in scattered '' 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. 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 14 April 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 27 May 2004, indicating over 92% of sampling exceeded 99.99% accuracy which was within the intended goal. In March 2009, the Genome Reference Consortium (GRC) released a more accurate version of the human genome, but that still left more than 300 gaps, while 160 such gaps remained in 2015. Though in May 2020 the GRC reported 79 "unresolved" gaps, accounting for as much as 5% of the human genome, months later, the application of new long-range sequencing techniques and a 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 X chromosome. Similarly, an end-to-end complete sequence of human autosomal chromosome 8 followed several months later. In April 2022, the Telomere-to-Telomere (T2T) consortium published a complete sequence of the non-
Y chromosome The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...
s, highlighting the 8% of the human genome that the HGP had not sequenced. The T2T consortium then used this newly completed genome sequence as a reference to identify over 2 million additional genomic variants. In August 2023, Rhie et al. reported the successful sequencing of the previously missing regions of the Y chromosome, achieving the full sequencing of all 24 human chromosomes.


Applications and proposed benefits

The sequencing of the human genome holds benefits for many fields, from molecular medicine to
human evolution ''Homo sapiens'' is a distinct species of the hominid family of primates, which also includes all the great apes. Over their evolutionary history, humans gradually developed traits such as Human skeletal changes due to bipedalism, bipedalism, de ...
. The Human Genome Project, through its sequencing of the DNA, can help researchers understand diseases including: genotyping of specific viruses to direct appropriate treatment; identification of
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s linked to different forms of cancer; the design of medication and more accurate prediction of their effects; advancement in
forensic Forensic science combines principles of law and science to investigate criminal activity. Through crime scene investigations and laboratory analysis, forensic scientists are able to link suspects to evidence. An example is determining the time and ...
applied sciences;
biofuel Biofuel is a fuel that is produced over a short time span from Biomass (energy), biomass, rather than by the very slow natural processes involved in the formation of fossil fuels such as oil. Biofuel can be produced from plants or from agricu ...
s and other energy applications; agriculture,
animal husbandry Animal husbandry is the branch of agriculture concerned with animals that are raised for meat, animal fiber, fibre, milk, or other products. It includes day-to-day care, management, production, nutrition, selective breeding, and the raising ...
, bioprocessing; risk assessment; bioarcheology,
anthropology Anthropology is the scientific study of humanity, concerned with human behavior, human biology, cultures, society, societies, and linguistics, in both the present and past, including archaic humans. Social anthropology studies patterns of behav ...
and
evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
. The sequence of the DNA is stored in
database In computing, a database is an organized collection of data or a type of data store based on the use of a database management system (DBMS), the software that interacts with end users, applications, and the database itself to capture and a ...
s available to anyone on the Internet. The US
National Center for Biotechnology Information The National Center for Biotechnology Information (NCBI) is part of the 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 NCBI is lo ...
(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 par ...
, along with sequences of known and hypothetical genes and proteins. Other organizations, such as the UCSC Genome Browser at the University of California, Santa Cruz, and Ensembl present additional data and annotation and powerful tools for visualizing and searching it. Computer programs have been developed to analyze the data because the data itself is difficult to interpret without such programs. Generally speaking, advances in genome sequencing technology have followed
Moore's Law Moore's law is the observation that the Transistor count, number of transistors in an integrated circuit (IC) doubles about every two years. Moore's law is an observation and Forecasting, projection of a historical trend. Rather than a law of ...
, 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 Human Genome Project. By 2023, the speed record for sequencing a genome was around five hours; more often, however, it takes weeks.


Techniques and analysis

The process of identifying the boundaries between genes and other features in a raw DNA sequence is called genome annotation and is in the domain of
bioinformatics Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
. 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. Subsequent projects sequenced the genomes of multiple distinct ethnic groups, though as of 2019 there is still only one "reference genome".


Findings

Key findings of the draft (2001) and complete (2004) genome sequences include: # There are approximately 22,300 protein-coding genes in human beings, the same range as in other mammals. # The human genome has significantly more segmental duplications (nearly identical, repeated sections of DNA) than had been previously suspected. # At the time when the draft sequence was published, fewer than 7% of protein families appeared to be vertebrate specific.


Accomplishments

The human genome has approximately 3.1 billion
base pair 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 ...
s. 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 A megaproject is an extremely large-scale construction and investment project. A more general definition is "Megaprojects are temporary endeavours (i.e. projects) characterised by: large investment commitment, vast complexity (especially in org ...
. The genome was broken into smaller pieces; approximately 150,000
base pair 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 ...
s in length. These pieces were then ligated into a type of vector known as "
bacterial artificial chromosome A bacterial artificial chromosome (BAC) is a DNA construct, based on a functional fertility plasmid (or F-plasmid), used for transforming and cloning in bacteria, usually '' E. coli''. F-plasmids play a crucial role because they contain partiti ...
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
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...
machinery. Each of these pieces was then sequenced separately as a small " shotgun" project and then assembled. The larger, 150,000 base pairs go together to create chromosomes. This is known as the " hierarchical shotgun" approach, because the genome is first broken into relatively large chunks, which are then mapped to chromosomes before being selected for sequencing. Funding came from the US government through the National Institutes of Health in the United States, and a UK charity organization, the
Wellcome Trust The Wellcome Trust is a charitable foundation focused on health research based in London, United Kingdom. It was established in 1936 with legacies from the pharmaceutical magnate Henry Wellcome (founder of Burroughs Wellcome, one of the predec ...
, as well as numerous other groups from around the world. The funding supported a number of large sequencing centers including those at Whitehead Institute, the
Wellcome Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit organisation, non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is l ...
(then called The Sanger Centre) based at the Wellcome Genome Campus, Washington University in St. Louis, and Baylor College of Medicine. The UN 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 $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
worm Worms are many different distantly related bilateria, bilateral animals that typically have a long cylindrical tube-like body, no limb (anatomy), limbs, and usually no eyes. Worms vary in size from microscopic to over in length for marine ...
, fly, and
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
genomes, funding of databases, development of new technologies, supporting bioinformatics and ethics programs, as well as polishing and assessment of the genome assembly. Both the Celera and public approaches spent roughly $250 million on the production sequencing effort. For sequence assembly, Celera made use of publicly available maps at
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 par ...
, which Celera was capable of generating, but the availability of which was "beneficial" to the privately-funded project. Celera used a technique called whole genome shotgun sequencing, employing 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 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 7 July 2000, the UCSC Genome Bioinformatics Group released the 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 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. The statement sent Celera's stock plummeting and dragged down the
biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...
-heavy
Nasdaq The Nasdaq Stock Market (; National Association of Securities Dealers Automated Quotations) is an American stock exchange based in New York City. It is the most active stock trading venue in the U.S. by volume, and ranked second on the list ...
. The biotechnology sector lost about $50 billion in
market capitalization Market capitalization, sometimes referred to as market cap, is the total value of a publicly traded company's outstanding common shares owned by stockholders. Market capitalization is equal to the market price per common share multiplied by ...
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 is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'' (which published the publicly funded project's 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,
press releases A press release (also known as a media release) is an official statement delivered to members of the news media for the purpose of providing new information, creating an official statement, or making an announcement directed for public releas ...
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 International Human Genome Sequencing Consortium (IHGSC) 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 A library is a collection of Book, books, and possibly other Document, materials and Media (communication), media, that is accessible for use by its members and members of allied institutions. Libraries provide physical (hard copies) or electron ...
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 reference genome produced by the public HGP came from a single anonymous male donor from
Buffalo, New York Buffalo is a Administrative divisions of New York (state), city in the U.S. state of New York (state), New York and county seat of Erie County, New York, Erie County. It lies in Western New York at the eastern end of Lake Erie, at the head of ...
, (
code name A code name, codename, call sign, or cryptonym is a code word or name used, sometimes clandestinely, to refer to another name, word, project, or person. Code names are often used for military purposes, or in espionage. They may also be used in ...
RP11; the "RP" refers to Roswell Park Comprehensive Cancer Center). HGP scientists used
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
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 X chromosome and one
Y chromosome The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...
) 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 In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a ...
(SNP) groups (called
haplotype A haplotype (haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material (DNA) which is inherited from two parents. Normally these organisms have their DNA orga ...
s, or "haps"). The DNA samples for the HapMap came from a total of 270 individuals;
Yoruba people The Yoruba people ( ; , , ) are a West African ethnic group who inhabit parts of Nigeria, Benin, and Togo, which are collectively referred to as Yorubaland. The Yoruba constitute more than 50 million people in Africa, are over a million outsid ...
in
Ibadan Ibadan (, ; ) is the Capital city, capital and most populous city of Oyo State, in Nigeria. It is the List of Nigerian cities by population, third-largest city by population in Nigeria after Lagos and Kano (city), Kano, with a total populatio ...
, Nigeria;
Japanese people are an East Asian ethnic group native to the Japanese archipelago. Japanese people constitute 97.4% of the population of the country of Japan. Worldwide, approximately 125 million people are of Japanese descent, making them list of contempora ...
in Tokyo;
Han Chinese The Han Chinese, alternatively the Han people, are an East Asian people, East Asian ethnic group native to Greater China. With a global population of over 1.4 billion, the Han Chinese are the list of contemporary ethnic groups, world's la ...
in 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 Northern Europe. In the Celera Genomics private-sector project, DNA from five different individuals was used for sequencing. The lead scientist of Celera Genomics at that time, Craig Venter, later acknowledged (in a public letter to the journal ''
Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
'') that his DNA was one of 21 samples in the pool, five of which were selected for use.


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 offer new avenues for advances in medicine and
biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...
. 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, hemostasis disorders,
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
,
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
diseases, and many others. Also, the etiologies for cancers,
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
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 may have narrowed down their search to a particular gene. By visiting the human genome database on the internet, 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 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. Analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of
evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
. In many cases, evolutionary questions can now be framed in terms of
molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
; indeed, many major evolutionary milestones (the emergence of the
ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...
and
organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...
s, the development of
embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...
s with body plans, the
vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
) can be related to the molecular level. Many questions about the similarities and differences between humans and their closest relatives (the
primate Primates is an order (biology), order of mammals, which is further divided into the Strepsirrhini, strepsirrhines, which include lemurs, galagos, and Lorisidae, lorisids; and the Haplorhini, haplorhines, which include Tarsiiformes, tarsiers a ...
s, and indeed the other
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
s) 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 '' 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 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 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 The Health Insurance Portability and Accountability Act of 1996 (HIPAA or the Ted Kennedy, Kennedy–Nancy Kassebaum, Kassebaum Act) is a United States Act of Congress enacted by the 104th United States Congress and signed into law by President ...
(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. 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. While 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 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." In July 2024, an investigation by Undark Magazine and co-published with STAT News revealed for the first time several ethical lapses by the scientists spearheading the Human Genome Project. Chief among these was the use of roughly 75 percent of a single donor's DNA in the construction of the reference genome, despite informed consent forms, provided to each of the 20 anonymous donors participating, that indicated no more than 10 percent of any one donor's DNA would be used. About 10 percent of the reference genome belonged to one of the project's lead scientists, Pieter De Jong.


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 billion 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.

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.

* ttps://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 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 RealPlayer, formerly RealAudio Player, RealOne Player and RealPlayer G2, is a cross-platform media player (software), media player app, developed by RealNetworks. The media player is compatible with numerous container file formats of the multimed ...
format.
Bioethics Research Library
Numerous original documents at Georgetown University.
David J. Galas
;Works by archive * **
Project Gutenberg Project Gutenberg (PG) is a volunteer effort to digitize and archive cultural works, as well as to "encourage the creation and distribution of eBooks." It was founded in 1971 by American writer Michael S. Hart and is the oldest digital li ...
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 throug
Human Genome Project, Chromosome Number 01
for Chromosome 1 sequentially t
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
supplementary information file
dated March 2004 which contains additional sequence information. * {{Authority control . Biotechnology 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 Bioinformatics