Human genome project how does it work

Miniaturization technology is facilitating the sequencing of more—and longer—DNA fragments in less time and increasing the portability of sequencing processes, a capability that is particularly important in clinical or field work. In , for example, the National Institutes of Health NIH , through its National Center for Human Genome Research NCHGR , began a new initiative for the development of microtechnologies to reduce the size of sequencing instrumentation and thereby increase the speed of the sequencing process.

NCHGR also is exploring new strategies for minimizing time-consuming sequencing bottlenecks by developing integrated, matched components that will help ensure that each step in the sequencing process proceeds as efficiently as possible. The overall sequencing rate is only as fast as its slowest step. Other developments in DNA sequencing have aimed to reduce the costs associated with the technology. Research on new DNA sequencing techniques is addressing the need for rapid, inexpensive, large-scale sequencing processes for comparison of complex genomes and clinical applications.

Further improvements in the efficiency of current processes, along with the development of entirely new approaches, will enable researchers to determine the complete sequence of the human genome perhaps before the year The detailed genetic, physical, and sequence maps developed by the Human Genome Project also will be critical to understanding the biological basis of complex disorders resulting from the interplay of multiple genetic and environmental influences, such as diabetes; heart disease; cancer; and psychiatric illnesses, including alcoholism.

In , for example, researchers used genetic maps to discover at least five different chromosome regions that appear to play a role in insulin-dependent i.

Analyses to identify the genetic components of these complex diseases require high-resolution genetic maps and must be conducted on a scale much larger than was previously possible. Automated microsatellite marker technology 3 now makes it possible to determine the genetic makeup i.

NCHGR is planning a technologically advanced genotyping facility to assist investigators in designing research studies; performing genetic analyses; and developing new techniques for analyzing common, multigene diseases.

Efforts to understand and treat disease processes at the DNA level are becoming the basis for a new molecular medicine. The discovery of disease-associated genes provides scientists with the foundation for understanding the course of disease, treating disorders with synthetic DNA or gene products, and assessing the risk for future disease.

Thus, by going directly to the genetic source of human illness, molecular medicine strategies will offer a more customized health management based on the unique genetic constitution of each person.

This approach will apply not only to classical, single-gene hereditary disorders but also to more common, multi-gene disorders, such as alcoholism. During the past 3 years, positional cloning has led to the isolation of more than 30 disease-associated genes. Although this number has increased dramatically, compared with the years predating the Human Genome Project, it is still a small fraction of the 50, to , genes that await discovery in the entire genome.

NCHGR has helped develop efficient biological and computer techniques to identify all the genes in large regions of the genome. One technique was used successfully last year to isolate BRCA1 , the first major gene linked to inherited breast cancer. A process that isolates the protein-coding sequences of a gene i. Clinical tests that detect disease-causing mutations in DNA are the most immediate commercial application of gene discovery.

These tests may positively identify the genetic origin of an active disease, foreshadow the development of a disease later in life, or identify healthy carriers of recessive diseases such as cystic fibrosis. Although DNA testing offers a powerful new tool for identifying and managing disease, it also poses several medical and technical challenges.

The number and type of mutations for a particular disease may be few, as in the case of achondroplasia, 5 or many, as in the case of cystic fibrosis and hereditary breast cancer.

Thus, it is essential to establish for each potential DNA test how often it detects disease-linked mutations and how often and to what degree detection of mutations correlates with the development of disease.

Gene discovery also provides opportunities for developing gene-based treatment for hereditary and acquired diseases. These treatment approaches range from the mass production of natural substances e. The top U. The translation of human genome technologies into patient care brings with it special concerns about how these tools will be applied. In the meantime, people who undergo genetic tests run the risk of discrimination in health insurance and may have difficulty adapting to test results—particularly in families in which hereditary disease is common—regardless of whether a test indicates future disease.

To help ensure that medical benefits are maximized without jeopardizing psychosocial and economic well-being, the Human Genome Project, from its beginning, has allocated a portion of its research dollars to study the ethical, legal, and social implications ELSI of the new genetic technologies. A diverse funding program supports research in four priority areas: the ethical issues surrounding the conduct of genetic research, the responsible integration of new genetic technologies into the clinic, the privacy and fair use of genetic information, and the professional and public education about these issues.

The task force will examine safety, accuracy, predictability, quality assurance, and counseling strategies for the responsible use of genetic tests. These 3-year studies are examining the psychosocial and patient-education issues related to testing healthy members of families with high incidences of cancer for the presence of mutations that greatly increase the risk of developing cancer. The results will provide a thorough base of knowledge on which to build plans for introducing genetic tests for cancer predisposition into medical practice.

Research in human genetics focuses not only on the causes of disease and disability but also on genes and genetic markers that appear to be associated with other human characteristics, such as height, weight, metabolism, learning ability, sexual orientation, and various behaviors Hamer et al.

Associating genes with human traits that vary widely in the population raises unique and potentially controversial social issues. Genetic studies elucidate only one component of these complex traits. The findings of these studies, however, may be interpreted to mean that such characteristics can be reduced to the expression of particular genes, thus excluding the contributions of psychosocial or environmental factors.

The Human Genome Project must therefore foster a better understanding of human genetic variation among the general public and health care professionals as well as offer research policy options to prevent genetic stigmatization, discrimination, and other misuses and misinterpretations of genetic information. Department of Health and Human Services and U.

Department of Energy After nearly 6 years, scientists involved in the Human Genome Project have met or exceeded most of those goals—some ahead of time and all under budget. Already, further technological advances make it likely that a new plan will be needed, perhaps as early as this year. In , an international consortium headed by the Genome Science and Technology Center in Iowa published a genetic map of the human genome containing almost 6, markers spaced less than 1 million nucleotides apart Cooperative Human Linkage Center et al.

This map was completed more than 1 year ahead of schedule, and its density of markers is four to six times greater than that called for by the goals. This early achievement is largely a result of the discovery and development of micro-satellite DNA markers and of large-scale methods for marker isolation and analysis. In a related project, technology developed so quickly that a high resolution genetic map of the mouse genome was completed in just 2 years.

NCHGR is now helping to coordinate an initiative with other NIH institutes, particularly the National Heart, Lung, and Blood Institute and the National Institute on Alcohol Abuse and Alcoholism, to develop a high-resolution genetic map of the rat, a useful model for studying complex disorders such as hypertension, diabetes, and alcoholism. The original 5-year goal to isolate contiguous DNA fragments that span at least 2 million nucleotides was met early on; soon, more than 90 percent of the human genome will be accounted for using sets of overlapping DNA fragments, each of which is at least 10 million nucleotides long.

Complete physical maps now exist for human chromosomes 21, 22, and Y. Nearly complete maps have been developed for chromosomes 3, 4, 7, 11, 12, 16, 19, and X.

As the end of the first phase of the Human Genome Project draws near, its impact already is rippling through basic biological research and clinical medicine.

From deciphering information in genes, researchers have gained new knowledge about the nature of mutations and how they cause disease. Furthermore, new paradigms will emerge as researchers and clinicians understand interactions between genes, the molecular basis of multigene disorders, and even tissue and organ function. Lander et al. Venter et al. Rather, they serve as a starting point for broad comparisons across humanity.

The knowledge obtained from the sequences applies to everyone because all humans share the same basic set of genes and genomic regulatory regions that control the development and maintenance of their biological structures and processes. In the international public-sector Human Genome Project HGP , researchers collected blood female or sperm male samples from a large number of donors. Only a few samples were processed as DNA resources.

Thus donors' identities were protected so neither they nor scientists could know whose DNA was sequenced. DNA clones from many libraries were used in the overall project. Technically, it is much easier to prepare DNA cleanly from sperm than from other cell types because of the much higher ratio of DNA to protein in sperm and the much smaller volume in which purifications can be done.

Sperm contain all chromosomes necessary for study, including equal numbers of cells with the X female or Y male sex chromosomes. However, HGP scientists also used white cells from female donors' blood to include samples originating from women.

In the Celera Genomics private-sector project, DNA from a few different genomes was mixed and processed for sequencing. Most SNPs have no physiological effect, although a minority contribute to the beneficial diversity of humanity. Marvin Stodolsky, formerly of the U. A list of the major U. Other individual researchers at numerous colleges, universities, and laboratories throughout the United States also received DOE and NIH funding for human genome research. After the atomic bomb was developed and used, the U.

Congress charged the Department of Energy's DOE predecessor agencies the Atomic Energy Commission and the Energy Research and Development Administration with studying and analyzing genome structure, replication, damage, and repair and the consequences of genetic mutations, especially those caused by radiation and chemical by-products of energy production.

From these studies grew the recognition that the best way to study these effects was to analyze the entire human genome to obtain a reference sequence.

Human Genome Project formally began October 1, , after the first joint 5-year plan was written and a memorandum of understanding was signed between the two organizations. The DOE Human Genome Program ELSI component and the data it generated concentrated on two main areas: 1 privacy and confidentiality of personal genetic information, including its accumulation in large, computerized databases and databanks; and 2 development of educational materials and activities in genome science and ELSI, including curricula and TV documentaries, workshops, and seminars for targeted audiences.

Other areas of interest include data privacy arising from potential uses of genetic testing in the workplace and issues related to commercialization of genome research results and technology transfer. Making the Project Possible Its long-standing mission to understand and characterize the potential health risks posed by energy use and production led DOE to propose, in the mids, that all three billion bases of DNA from an "average" human should be sequenced.

Technologies available before that time had not enabled the routine detection of extremely rare and often minute genetic changes resulting from radiation and chemical exposures. In most cases, the DOE successes outlined below were the result of basic research programs.

Research is an incremental process that learns from both the successes and failures of other research investments, including those at other agencies and organizations. In addition, no single instrument, technology, reagent, or protocol made high-throughput DNA sequencing possible, many contributors were responsible.

Richard Mathies at U. Norman Dovichi at the University of Alberta. These high-throughput instruments are one of the keys to the success of the genome project. DOE-funded research contributed to the development of fluorescent dyes that increased the accuracy and safety of DNA sequencing as well as the ability to automate the procedures. DNA cloning vectors Before large DNA molecules can be sequenced, they are cut into small pieces and multiplied, or cloned, into numerous copies using microbial-based "cloning" vectors.

Today, the bacterial artificial chromosome BAC is the most commonly used vector for initial DNA amplification before sequencing. These cloning vectors were developed with DOE funds. BAC-end sequencing The widely agreed-upon strategy for sequencing the human genome is based on the use of BACs that carry fragments of human DNA from known locations in the genome. DOE-funded research at The Institute for Genomic Research in Rockville, Maryland, and at the University of Washington provided the sequencing community with a complete set of over , BAC-based genetic "markers" corresponding to a sequence tag every 3 to 4 kilobases across the entire human genome.

These markers were needed to assemble both the draft and the final human DNA sequence. This powerful analytical tool was developed with DOE funds by Dr. Project goals were to. Since , the DOE Genomic Science Program has been using microbial and plant genomic data, high-throughput analytical technologies, and modeling and simulation to develop a predictive understanding of biological systems behavior relevant to solutions for energy and environmental challenges including bioenergy production, environmental remediation, and climate stabilization.

During the Human Genome Project, this website served as the primary electronic information source for HGP researchers and the public. It is now a unique archive—a repository for historical documents detailing the history of the HGP from the project's beginnings in until it was completed in Primary goals were to discover the complete set of human genes and make them accessible for further biological study, and determine the complete sequence of DNA bases in the human genome.

See Timeline for more HGP history. Published from until , this newsletter facilitated HGP communication, helped prevent duplication of research effort, and informed persons interested in genome research. Unless otherwise noted, publications and webpages on this site were created for the U. Department of Energy program and are in the public domain.

Permission to use these documents is not needed, but credit the U.