The Human Genome Project

One of the most important research projects, in the history of biology, is the Human Genome Project. It is a project designed to identify all 3 billion DNA bases that contain all of the information necessary to make a human being. We would like a complete sequence of the entire human DNA, but there is much more to the Human Genome Project than generating the sequence of human DNA. No two people have the same DNA except for identical twins. The human genome project is studying the differences between DNA sequences between individuals. The project is also involved in studying the DNA sequences in many other organisms that have served well for the last 30, 40 or even 90 years for our studies of genetics. Bacteria, E-coli, yeast, fruit flies, worms, and mice can teach us about normal processes that take place in humans as well as other forms of life. ( www.thefreelibrary.com/Human+Genome+Project.)

DESCRIPTION

The Human Genome Project (HGP) was one of the great feats of exploration in history an inward voyage of discovery rather than an outward exploration of the planet or the cosmos; an international research effort to sequence and map all of the genes - together known as the genome - of members of our species, Homo sapiens. Completed in April 2003, the HGP gave us the ability to, for the first time, to read nature's complete genetic blueprint for building a human being. Begun formally in 1990, the U.S. Human Genome Project was a 13-year effort coordinated by the U.S. Department of Energy and the National Institutes of Health. The project originally was planned to last 15 years, but rapid technological advances accelerated the completion date to 2003. Project goals were to identify all the approximately 20,000-25,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up human DNA, store this information in databases, improve tools for data analysis, transfer related technologies to the private sector, and address the ethical, legal, and social issues (ELSI) that may arise from the project.

To help achieve these goals, researchers also studied the genetic makeup of several nonhuman organisms. These include the common human gut bacterium Escherichia coli, the fruit fly, and the laboratory mouse. A unique aspect of the U.S. Human Genome Project is that it was the first large scientific undertaking to address potential ELSI implications arising from project data. Another important feature of the project was the federal government's long-standing dedication to the transfer of technology to the private sector. By licensing technologies to private companies and awarding grants for innovative research, the project catalyzed the multibillion-dollar U.S. biotechnology industry and fostered the development of new medical applications. Landmark papers detailing sequence and analysis of the human genome were published in February 2001 and April 2003 issues of Nature and Science.

Tools being used

The tools created through the HGP also continue to inform efforts to characterize the entire genomes of several other organisms used extensively in biological research, such as mice, fruit flies and flatworms. These efforts support each other, because most organisms have many similar, "homologous," genes with similar functions. Therefore, the identification of the sequence or function of a gene in a model organism, for example, the

roundworm C. elegans, has the potential to explain a homologous gene in human beings, or in one of the other model organisms. These ambitious goals required and will continue to demand a variety of new technologies that have made it possible to relatively rapidly construct a first draft of the human genome and to continue to refine that draft. These techniques include: DNA Sequencing The Employment of Restriction Fragment-Length Polymorphisms (RFLP) Yeast Artificial Chromosomes (YAC) Bacterial Artificial Chromosomes (BAC) The Polymerase Chain Reaction (PCR) Electrophoresis Of course, information is only as good as the ability to use it. Therefore, advanced methods for widely Disseminating the information generated by the HGP to scientists, physicians and others, is necessary in Order to ensure the most rapid application of research results for the benefit of humanity. Biomedical Technology and research are particular beneficiaries of the HGP. A BRIEF HISTORY In February 2001, the Human Genome Project (HGP) published its results to that date: a 90 percent complete sequence of all three billion base pairs in the human genome. The HGP consortium published its data in the February 15, 2001, issue of the journal Nature. The project had its ideological origins in the mid-1980s, but its intellectual roots stretch back further. Alfred Sturtevant created the first Drosophila gene map in 1911. The crucial first step in molecular genome analysis, and in much of the molecular biological research of the last half-century, was the discovery of the double helical structure of the DNA molecule in 1953 by Francis Crick and James Watson. The two researchers shared the 1962 Nobel Prize (along with Maurice Wilkins) in the category of "physiology or medicine." In the mid-1970s, Frederick Sanger developed techniques to sequence DNA, for which he received his second Nobel Prize in chemistry in 1980. (His first, in 1958, was for studies of protein structure). With the automation of DNA sequencing in the 1980s, the idea of analyzing the entire human genome was first Proposed by a few academic biologists. The United States Department of Energy, seeking data on protecting the genome from the mutagenic (gene-mutating) effects of radiation, became involved in 1986, and established an early genome Project in 1987. In 1988, Congress funded both the NIH and the DOE to embark on further exploration of this concept, and the two government agencies formalized an agreement by signing a Memorandum of Understanding to "coordinate research and technical activities related to the human genome." James Watson was appointed to lead the NIH component, which was dubbed the Office of Human Genome Research. The following year, the Office of Human Genome Research evolved into the National Center for Human Genome Research (NCHGR). In 1990, the initial planning stage was completed with the publication of a joint research plan, "Understanding Our Genetic Inheritance: The Human Genome Project, The First Five Years, FY 1991-1995." This initial research plan set out specific goals for the first five years of what was then projected to be a 15- year research effort. In 1992, Watson resigned, and Michael Gottesman was appointed acting director of the center. The following year, Francis S. Collins was named director. The advent and employment of improved research techniques, including the use of restriction fragment length polymorphisms, the polymerase chain reaction, bacterial and yeast artificial chromosomes and pulsed-field gel electrophoresis, enabled rapid early progress. Therefore, the 1990 plan was updated with a new five-year plan announced in 1993 in the journal Science (262: 43-46; 1993). Indeed, a large part of the early work of the HGP was devoted to the development of improved technologies for accelerating the elucidation

of the genome. In a 2001 article in the journal Genome Research, Collins wrote, "Building detailed genetic and physical maps, developing better, cheaper and faster technologies for handling DNA, and mapping and sequencing the more modest-sized genomes of model organisms were all critical stepping stones on the path to initiating the large-scale sequencing of the human genome." Also in 1993, the NCHGR established a Division of Intramural Research (DIR), in which genome technology is developed and used to study specific diseases. By 1996, eight NIH institutes and centers had also collaborated to create the Center for Inherited Disease Research (CIDR), for study of the genetics of Complex diseases. In 1997, the NCHGR received full institute status at NIH, becoming the National Human Genome Research Institute in 1997, with Collins remaining as the director for the new institute. A third five-year plan was announced in 1998, again in Science, (282: 682-689; 1998). In June 2000 came the announcement that the majority of the human genome had in fact been sequenced, which was followed by the publication of 90 percent of the sequence of the genome's three billion base-pairs in the journal Nature, in February 2001. On April 14, 2003 the National Human Genome Research Institute (NHGRI), the Department of Energy (DOE) and their partners in the International Human Genome Sequencing Consortium announced the successful completion of the Human Genome Project. (http://genomics.energy.gov)

What was the Human Genome Project and why has it been Important?
The Human Genome Project was an international research effort to determine the Sequence of the human genome and identify the genes that it contains. The Project was Coordinated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, and China. The Human Genome Project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule. The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences.

What were the goals of the Human Genome Project?

The main goals of the Human Genome Project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The Project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. In addition to sequencing DNA, the Human Genome Project sought to develop new tools to Obtain and analyze the data and to make this information widely available. Also, because advances in genetics have consequences for individuals and society, the Human Genome Project committed to exploring the consequences of genomic research through its Ethical, Legal, and Social Implications (ELSI) program.

What did the Human Genome Project accomplish?

In April 2003, researchers announced that the Human Genome Project had completed a high-quality sequence of essentially the entire human genome. This sequence closed the gaps from a working draft of the genome, which was published in 2001. It also identified the locations of many human genes and provided information about their structure and organization. The Project made the sequence of the human genome and tools to analyze the data freely available via the Internet. In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including brewers yeast, the roundworm, and the fruit fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life. (www.4shared.com Human genome project molecular biology )

Project Sponsors
The U.S. Department of Energy funded its Human Genome Program through their Office
of Biological and Environmental Research. (genome@science.doe.gov). The U.S. National Institutes of Health funded its program through the National Human Genome Research Institute (NHGRI). TIMELINE OF HUMAN GENOME PROJECT

1985 Robert Sinsheimer holds meeting on human genome sequencing at University of California, Santa Cruz. At OHER Charles DeLisi and David A. Smith commission the first Santa Fe conference to assess the feasibility of a Human Genome Initiative. 1986 Following the Santa Fe conference, DOE OHER announces Human Genome Initiative. With $5.3 million, pilot projects begin at DOE national laboratories to develop critical resources and technologies. First Santa Fe Conference is held, March 3-4, 1986. 1987 Congressionally chartered DOE advisory committee, HERAC, recommends a 15-year, multidisciplinary, scientific, and technological undertaking to map and sequence the human genome. DOE designates multidisciplinary human genome centers. NIH NIGMS begins funding of genome projects. 1988 HUGO founded by scientists to coordinate efforts internationally. First annual Cold Spring Harbor Laboratory meeting on human genome mapping and sequencing. Telomere (chromosome end) sequence having implications for aging and cancer research is identified at LANL.

1989 DNA STSs recommended to correlate diverse types of DNA clones. DOE and NIH establish Joint ELSI Working Group. 1990 DOE and NIH present joint 5-year U.S. HGP plan to Congress . The 15year project formally begins. Projects begun to mark gene sites on chromosome maps as sites of mRNA expression. 1993 International IMAGE Consortium established to coordinate efficient mapping and sequencing of gene-representing cDNAs. DOE-NIH ELSI Working Group's Task Force on Genetic and Insurance Information releases recommendations. DOE and NIH revise 5-year goals IOM releases U.S. HGP-funded report, "Assessing Genetic Risks." LBNL implements novel transpose-mediated chromosome-sequencing system. GRAIL sequence-interpretation service provides Internet access at ORNL. 1992 Low-resolution genetic linkage map of entire human genome published. 1991 Human chromosome mapping data repository, GDB, established. 1994 Genetic-mapping 5-year goal achieved 1 year ahead of schedule. Completion of second-generation DNA clone libraries representing each human chromosome by LLNL and LBNL. Genetic Privacy Act, first U.S. HGP legislative product, proposed to regulate collection, analysis, storage, and use of DNA samples and genetic information obtained from them; endorsed by ELSI Working Group. DOE MGP launched ; spin-off of HGP. DOE HGP Information Web site activated for public and researchers. 1995 LANL and LLNL announce high-resolution physical maps of chromosome 16 and chromosome 19, respectively. Moderate-resolution maps of chromosomes 3, 11, 12, and 22 maps published. Physical map with over 15,000 STS markers published. First (nonviral) whole genome sequenced (for the bacterium Homophiles influenza). Sequence of smallest bacterium, Mycoplasma genitalium , completed; provides a model of the minimum number of genes needed for independent existence.

EEOC guidelines extend ADA employment protection to cover discrimination based on genetic information related to illness, disease, or other conditions. 1996 Methanococcus jannaschii genome sequenced; confirms existence of third major branch of life on Earth. Health Care Portability and Accountability Act prohibits use of genetic information in certain health insurance eligibility decisions, requires DHHS to enforce health-information privacy provisions. DOE and NCHGR issue guidelines on use of human subjects for largescale sequencing projects. Saccharomyces cerevisiae (yeast) genome sequence completed by international consortium. Sequence of the human T-cell receptor region completed. 1997 Escherichia coli genome sequence completed. Second large-scale sequencing strategy meeting held in Bermuda. High-resolution physical maps of chromosomes X and 7 completed. DOE forms Joint Genome Institute for implementing high-throughput activities at DOE human Genome centers, initially in sequencing and functional genomics. 1998 Caenorhabditis elegance genome sequence completed. DOE and NIH reveal new five-year plan for HGP, predict project completion by 2003. JGI exceeds sequencing goal , achieves 20 Mb for FY 1998. GeneMap'98 containing 30,000 markers released. Incyte Pharmaceuticals announces plans to sequence human genome in 2 years. Mycobacterium tuberculosis bacterium sequenced. Celera Genomics formed to sequence much of human genome in 3 years using HGP-generated Resources. Largest-ever ELSI meeting attended by over 800 from diverse disciplines and sponsored by DOE; Whitehead Institute; and the American Society of Law, Medicine, and Ethics. Human Genome Project passes midpoint. 1999 First Human Chromosome Completely Sequenced - Chromosome 22. HGP advances goal for obtaining a draft sequence of the entire human genome from 2001 to 2000. 2000 HGP leaders and President Clinton announce the completion of a "working draft" DNA sequence of the human genome.

International research consortium publishes chromosome 21 genome, the smallest human chromosome and the second to be completely sequenced. DOE researchers announce completion of chromosomes 5, 16, and 19 draft sequences. International collaborators publish genome of fruit fly Drosophila melanogaster. Human Chromosome 20 Finished - Chromosome 20 is the third chromosome completely sequenced to the high quality specified by the Human Genome Project. Publication of Initial Working Draft Sequence February 12, 2001 Special issues of Science (Feb. 16, 2001) and Nature (Feb. 15, 2001) contain the working draft of the human genome sequence. Nature papers include initial analysis of the descriptions of the sequence generated by the publicly sponsored Human Genome Project, while Science publications focus on the draft sequence reported by the private company, Celera Genomics. A press conference was held at 10 a.m., Monday, February 12, 2001, to discuss the landmark publications. Pieter de Jong's team (now at the Oakland Children's Hospital, Oakland, CA) was a major provider of the BAC libraries used in the sequencing of the human and several other genomes. 2002 Mouse Genome Sequencing Consortium publishes its draft sequence of mouse genome in the December 5, 2002, issue of Nature. International consortium led by the DOE Joint Genome Institute publishes draft sequence of Fugu rubripes. 2003 Human Chromosome 6 Completed, October 2003. Human Chromosome 7 Completed, July 2003. Human Chromosome Y Completed, June 2003. Human Genome Project Declared Complete, April 2003 [ Human Chromosome 14 Finished 2004 Human Chromosome 16 Completed, December 2004. Landmark Paper: Finishing the euchromatic sequence of the human genome, Nature, Oct. 21, 2004 Human Gene Count Estimates Changed to 20,000 to 25,000, October 2004. Human Chromosome 5 Completed, September 2004. Landmark Paper: Human genome: Quality assessment of the human genome sequence. Nature 429, 365-368 (27 May 2004) Human Chromosome 9 Completed, May 2004. Human Chromosome 10 Completed, May 2004. Human Chromosome 18 Completed, March 2004. Human Chromosome 19 Completed, March 2004. Human Chromosome 13 Completed, March 2004

2005 Human Chromosome 4 Completed, April 2005. Human Chromosome 2 Completed, April 2005. Human Chromosome X Completed, March 2005. 2006 Human Chromosome 1 Completed, May 2006. Human Chromosome 3 Completed, April 2006. Human Chromosome 17 Completed, April 2006. Human Chromosome 11 Completed, March 2006. Human Chromosome 12 Completed, March 2006. Human Chromosome 15 Completed, March 2006. Human Chromosome 8 Completed, January 2006. 2008 Genetic Information Nondiscrimination Act (GINA) Becomes Law, May 2008. Landmark Paper: Mapping and sequencing of structural variation from eight human genomes, (Nature, May 1, 2008) (http://www.genome.gov) Ethical, Legal, and Social Issues

Examine issues surrounding the completion of the human DNA sequence and the study of human genetic variation. Examine issues raised by the integration of genetic technologies and information into health care and public health activities. Examine issues raised by the integration of knowledge about genomics and gene-environment interactions in non-clinical settings. Explore how new genetic knowledge may interact with a variety of philosophical, theological, and ethical perspectives.

Explore how racial, ethnic, and socioeconomic factors affect the use, understanding, and interpretation of genetic information; the use of genetic services; and the development of policy. (www.scribd.com )
BOOKS Genetics A Conceptual Approach - Pierce, B. A. Bioinformatics Sequence and Genome Analysis - David W. Mount. From Genes to Genomes - Concepts and Applications of DNA Technology. Dale