The National Human Genome Research Institute (NHGRI) was originally established as the National Center for Human Genome Research (NCHGR) in 1989. Its primary mission was to lead the National Institutes of Health (NIH) contribution to the Human Genome Project - an international research effort to determine the location of all human genes and to read the entire set of genetic instructions encoded in human DNA. This mission was completed in April 2003 with publication of the full and complete sequence of the human genome.
NHGRI carried out this mission by providing financial support to scientists at university, and other, public research laboratories throughout the United States. In addition to supporting the Human Genome Project, NHGRI established a Division of Intramural Research in 1993 to develop genome technologies that will accelerate the process of identifying and understanding the molecular basis of human genetic diseases.
The Human Genome Project (HGP) officially began in 1990 and was coordinated in the United States by the NHGRI and the U.S. Department of Energy (DOE). International HGP partners included the United Kingdom, France, Germany, Japan and China. Once scientists completed the ultimate task of sequencing all 3 billion base pairs in the human genome, they created a virtual blueprint for a human being.
From 1990 to 1994, the activities of the HGP were primarily devoted to developing genetic and physical maps that allowed precise localization of genes, and exploring technologies that enabled the sequencing of very large amounts of DNA with high accuracy and low cost. Pilot projects were initiated in 1996 to explore the feasibility of such large-scale sequencing of human DNA. These projects were extremely successful and resulted in creative laboratory innovations that automated and accelerated the sequencing process. By September 1997, the pilot projects had sequenced approximately two percent of human DNA. Eventually, with current technology, HGP centers were able to sequence 1,000 base pairs per second at a very low cost.
Scientific leaders of the Human Genome Project also made an important decision in 1996 - to deposit sequence in public databases within 24 hours of its assembly, with no restrictions on its use or redistribution. This defining moment in the HGP made the sequence immediately available to anyone with an Internet connection, ensuring that the sequence would ultimately benefit the public by empowering all the world's best minds.
In June 2000, the International Human Genome Sequencing Consortium announced that a "working draft" sequence of the human genome, nearly 90 percent complete, had been produced. In February 2001, the consortium published this sequence and an initial analysis of the human genome that reported a number of discoveries. The most surprising of these was that humans have only 30,000 to 35,000 genes, whereas previous predictions had ranged from 80,000 to 150,000 genes.
The Human Genome Project's goal of producing a highly accurate "finished" sequence was met in April 2003 - under budget and two years ahead of the original schedule. With the completion of the HGP, the mission of the NHGRI has expanded to encompass a broad range of studies aimed at understanding the structure and function of the human genome and its role in health and disease.
The ENCODE Project (ENCyclopedia Of DNA Elements) is a highly interactive public research consortium developed by NHGRI to carry out a pilot project for testing and comparing existing and new methods to identify functional sequences in DNA. Working together in a highly cooperative effort to rigorously analyze a defined portion of the human genome sequence, investigators with diverse backgrounds and expertise evaluate the relative merits of each of a diverse set of techniques, technologies and strategies in identifying all the functional elements in human genomic sequence, identify gaps in our ability to annotate genomic sequence, consider the abilities of such methods to be scaled up for an effort to analyze the entire human genome.
Mapping, sequencing and analyzing the genomes of other organisms also are goals critical to the HGP and NHGRI because these genomes help researchers characterize and interpret the human genome. Comparing human DNA sequences with those of different organisms allows scientists to identify regions of the human genome that likely play a vital role in our biological processes because they have been conserved through time and evolution. By improving our understanding of how human genes work, this research can lead to insights into treating and preventing human disease. From the outset of the HGP, certain "model" organisms were chosen for genome sequencing in addition to humans. The genomes of the bacterium Escherichia coli; Saccharomyces cerevisiae (commonly known as baker's yeast); Drosophila melanogaster (the fruitfly); and Caenorhabditis elegans (the multi-cellular roundworm) have already been sequenced.
In addition, the genomes of the laboratory mouse and rat, animals widely used in biology as models for understanding, treating, and preventing human diseases, have now been sequenced. Due to the tremendous capacity now available for sequencing genomic DNA and because of its research value, NHGRI recently introduced a process by which any researcher can propose a new model organism for genomic analysis, including complete genome sequencing.
Sequencing so many organisms has created a flood of data that must be analyzed and understood. NHGRI is meeting this challenge by fostering the creation of new resources and the involvement of investigators at all levels. The Centers of Excellence in Genomic Science (CEGS) is a program designed to encourage academic centers to pursue advanced genome research using the new technologies and large databases developed by the HGP. The CEGS program challenges the entire biomedical research community to form multi-investigator, interdisciplinary teams to develop novel and innovative genomic research projects. CEGS projects will develop new methods and technologies for collecting, interpreting and/or using genomic data sets that can be employed by the broader biomedical research community.
NHGRI has a range of further important genetic and genomic research pursuits beyond its best-known goal of sequencing the human genome, including working to understand the way individuals differ from each other at the genetic level, and the impact these variations may have on health. (See: Genetic Variation Program)
The HGP and its partners are creating a catalogue of the places in the genome where the DNA sequence differs among individuals. The most common variations are known as single nucleotide polymorphisms, or SNPs (pronounced "snips"). These are places where the DNA sequence varies by a single base, or DNA letter. NHGRI research complements the work of a non-profit international group, The SNP Consortium (TSC). Through combined efforts, nearly 3 million SNPs have already been identified and made available in public databases.
Scientists use SNPs to scan the entire genome, looking for chromosomal regions that are statistically associated with disease. A researcher can then refer to the working draft of the human genome to find the genes in those regions and narrow his or her search for the disease-causing alterations. SNPs will help scientists pinpoint genetic differences that predispose some, but not others to disease, and could help to explain some individuals' different responses to medical treatment.
The next key step in learning from the HGP is to generate a new map of the patterns of genetic variations across populations, known as the Haplotype Map (See: International HapMap Project). The SNP variants do not occur at random, but are correlated in important ways with their neighbors. By finding the pattern of variation along chromosomes, scientists can select a much smaller set of SNPs distributed along the chromosomes that will represent nearly all the underlying patterns of variation. This ?haplotype map? will be another critical resource for researchers trying to identify and understand the genetic basis of common human diseases.
As a result of the completed HGP, new disease genes are already discovered almost weekly. Recent successes by NHGRI?s intramural researchers include discovery of genes for prostate cancer, breast cancer, holoprosencephaly, progeria and Alzheimer's disease. Once scientists have identified a disease gene, they can begin to understand the illness at a molecular level. Over time, this can lead to the development of treatments, prevention strategies and accurate diagnostic tests, which in some instances can be life saving.
NHGRI intramural investigators also lead in the development of new genomic technologies. Microarrays, also known as "DNA chips," are among their breakthrough developments. These miniature devices allow thousands of DNA experiments to be carried out in a "laboratory" smaller than a credit card. Microarrays are produced by robots capable of placing thousands of microscopic spots of DNA on a small "chip." Each spot contains a different gene, so researchers can use this chip technology to see which genes are active, or "turned on," in different types of tumors, for example, or to identify specific gene mutations. This knowledge can provide more precise diagnostic criteria for different cancers and more individualized and effective treatments.
NHGRI researchers recently used these DNA chips to distinguish several closely related types of childhood cancer. Using typical diagnostic techniques, these cancers can be difficult to tell apart because they look alike under a microscope, which can lead to misdiagnosis and improper treatment. Collaborating with scientists at Lund University in Sweden, NHGRI investigators designed a novel method of combining DNA chip technology with a form of artificial intelligence called an artificial neural network (ANN). This new combined technology can differentiate these similar cancers by rapidly analyzing large amounts of data, allowing for highly accurate diagnoses.
In addition to studying disorders that arise from errors in a single gene, NHGRI scientists are investigating new strategies to tease apart the genetic and environmental contributors to common, more complex, disorders, such as diabetes, many cancers and even mental illnesses. Very fast, or "high throughput," technologies for identifying genes are crucial to studying such complex diseases.
The Center for Inherited Disease Research (CIDR) is a joint effort by twelve NIH institutes, with NHGRI serving as its lead agency, located on the Bayview campus of The Johns Hopkins University. The CIDR, with the capacity to perform more than 5.7 million genotypes per year, provides researchers with high-throughput genotyping services as well as advice on study design, sophisticated data warehousing technologies and database assistance.
Since its founding, NHGRI has understood the need to analyze the ethical, legal and social implications of genetic research and to address the issues they raise. The Ethical, Legal and Social Implications (ELSI) Research Program at NHGRI was established in 1990 as an integral part of the U.S. Human Genome Project. The ELSI research program funds and manages research grants and education projects at institutions throughout the United States and supports workshops, research consortia and policy conferences related to these projects.
NHGRI's ELSI Research Program is currently the largest federal supporter of bioethics research in the country, with an annual budget of almost $15 million. Four areas of research have been established as priorities: privacy and fairness in the use and interpretation of genetic information; responsible clinical integration of genetic technologies; issues surrounding genetics research; and public and professional education about these issues.
In particular, the ELSI program works to ensure the responsible use of genetic information. Along with the benefits of major advances in genetics and genomics, such as genetic testing for patients and their families, there is the potential for misinterpretation and misuse of this information. NHGRI and the ELSI program support legislation to prohibit the use of genetic information to discriminate against individuals. President Clinton signed the "Executive Order To Prohibit Discrimination in Federal Employment Based on Genetic Information" on February 8, 2000. The order prohibits federal government agencies from obtaining genetic information from employees or job applicants and from using genetic information in hiring and promotion decisions.
On October 14, 2003, the U.S. Senate passed the Genetic Information Nondiscrimination Act of 2003 (S. 1053) by a vote of 95-0. This is the first time the Senate has passed a bipartisan genetic nondiscrimination bill. The bill represents more than a year of good faith negotiation between the two parties. It would prevent health insurers and employers from using genetic information to determine eligibility, set premiums, or hire and fire people. It is now left to the House to pass the bill and for the President to sign it. The NHGRI has been working on the issue of genetic discrimination since 1995.
Last Reviewed: April 4, 2011