Expressed sequence tags

Related Terms

Adenine, biotechnology, Cancer Genome Atlas, cytosine, deoxyribonucleic acid, DNA, double helix, expressed sequence tags, gene, genetic disease, genetic disorders, genetic research, genetic testing, geneticists, genetics, genome, genomics, guanine, HapMap, heredity, human genome, inherited diseases, inherited disorders, mouse genome, nitrogen, TCGA, thymine.

Background

The Human Genome Project (HGP), which began in 1990, was an international research program that was designed to map out all of the genes that make up human beings. All of the genes in a single organism are called the genome.
Genes are found inside the cells of all organisms. An individual's genes are present in a large molecule called DNA (deoxyribonucleic acid), which looks like a twisted ladder. This unique shape is called a double helix. The sides of the double helix are made of alternating sugar and phosphate molecules. The "rungs" of the "ladder" are made of smaller molecules that contain nitrogen. These molecules include adenine, thymine, cytosine, and guanine.
All genes are made up of different combinations of these four molecules, which are arranged in different lengths. The sequence of these molecules provides the "code," or instructions, for each of the genes involved in the development, growth, and function of all the cells in the body.
Researchers from the United States, China, France, German, Japan, and the United Kingdom participated in the $3-billion human genome project. The goal of the HGP was to provide researchers with tools to understand the genetic factors related to inherited human diseases. Researchers hoped that understanding the human genome would lead to new strategies to diagnose, treat, and prevent inherited disorders, such as Down syndrome and Huntington's disease.
The project, which was expected to take 15 years to complete, was finished after 13 years. The project also cost less than expected ($2.7 billion).
HGP researchers have discovered that about 30,000-40,000 different genes are present in the cells of each human being. Researchers have identified the exact order and location of these genes in humans and other species. They have also developed linkage maps, which track the inheritance of genetic diseases over generations.

Methods

The Human Genome Project (HGP), which began in 1990, was an international research program that was designed to map out all of the genes that make up human beings (called the human genome), as well as their respective hereditary characteristic controls. The genome was completed in 2003. Researchers are still studying it in order to improve the treatments, prevention strategies, and diagnostic techniques for genetic disorders, such as Down syndrome and Huntington's disease.

Research

1990: In 1990, the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH) presented the Human Genome Project (HGP) to Congress. The government approved the research project, and the HGP formally began.
1994: In 1994, a detailed human genome map was completed one year ahead of schedule. This map allowed researchers to see where genes are located in specific chromosomes.
1995: In 1995, a physical map of the human genome was completed. This map arranged large segments of DNA in order.
1996: In 1996, the genetic map of the mouse was completed. This was considered an important milestone because mice and humans share about 85% of their genes. This is why scientists often study human diseases and drugs in mice.
Scientists also created a map that labeled the locations of expressed sequence tags (ESTs), which represent fragments of more than 16,000 genes in the human genome.
In addition, researchers from the National Human Genome Research Institute funded pilot projects to determine the best way to sequence the entire human genome. These projects tested the accuracy and feasibility of large-scale sequencing. They also took into consideration how expensive other approaches might be.
1998: In 1998, HGP researchers released a gene map that included 30,000 human genes that were believed to represent about one-third of all of the human genes.
1999: In 1999, HGP researchers finished the first completed sequence of a human chromosome: chromosome 22. Researchers chose to sequence this chromosome because it is a relatively small chromosome, and detailed maps of the chromosome had already been developed. The genes were sequenced in both the long and short arm of the chromosome. The long arm contains at least 545 genes and is 33,400,000 base pairs in length.
2000: In 2000, researchers from Harvard Medical School used gene splicing techniques to produce fruit flies that exhibited symptoms of Parkinson's disease. Researchers inserted mutated genes that were suspected causes of Parkinson's disease. The scientists used fruit flies because they have a short life cycle, which makes it easy to quickly test theories about specific genes associated with Parkinson's disease and possible treatments.
2001: In 2001, the National Human Genome Research Institute (NHGRI), the DOE, and their partners in the International Human Genome Sequencing Consortium published the first draft of the human genome that was 90% complete in the journal Nature.
2002: In 2002, researchers used a family-based study to link bipolar disorder (BP) to a specific gene. The scientists analyzed blood samples from 283 families with histories of this psychological illness. The researchers concluded that genetics appears to play a role in the development of BP.
2003: In 2003, researchers from the Human Genome Project (HGP) completed the human genome and found that there are 30,000-40,000 genes in each human. This number surprised the research community, because it was initially estimated that a human had anywhere from 50,000 to 140,000 genes.
Present: The completed human genome provides detailed information about the structure, organization, and function of human genes. This information is a basic set of instructions, or blueprint, for the development and function of a human being.
The completion of the HGP has led researchers to study the genome of other organisms, including mice, fruit flies, and flatworms. Researchers believe that identifying genes in other organisms may help them understand human genes better.

Implications

General: The completed human genome is similar to having an instructional map on how to make a human body. Researchers are now faced with the challenge of interpreting these so-called instructions in order to determine how genes work together in human health and disease. Scientists believe that genome-based research will lead to improved tools to diagnose, treat, and prevent inherited disorders, such as Huntington's disease.
Human diseases: In 2005, the international HapMap Project was developed to use information from the Human Genome Project (HGP) to research genes involved in common human diseases. This initiative has led to the discovery of more than 1,800 genes that are associated with inherited disorders. Researchers from HapMap have found genetic factors that are related to conditions, such as obesity and age-related blindness.
Today, as a result of the HGP, researchers are able to find a gene that is suspected of causing a specific disease in only a few days.
Genetic testing: The results of the HGP have led to the development of more than 1,000 genetic tests for inherited human diseases and disorders. These tests allow patients to learn their risks of developing certain diseases. They are also used to diagnose inherited medical conditions.
Biomedical products: The biomedical technology industry has also benefited from the completed human genome. Since the human genome was completed, many new technologies that use living cells and/or biological molecules have been designed. For instance, scientists are studying the safety and effectiveness of gene therapy, which involves inserting human genes into a patient as a possibly way to treat or prevent inherited disorders and some types of cancer. Currently, at least 350 biotechnology-based products are undergoing clinical trials. Patients should keep in mind that is usually takes more than 10 years for a company to perform the necessary studies in order to gain approval by the U.S. Food and Drug Administration (FDA).
Stem cell research: The completion of the HGP has also led to stem cell research. Stem cells are unspecialized cells that can potentially develop into different types of specialized cells. These cells may help treat diseases that are currently incurable, such as Alzheimer's disease, Parkinson's disease, or multiple sclerosis (MS). There are three types of stem cells: adult stem cells, embryonic stem cells, and umbilical cord stem cells.
Adult stem cells are present in many human body tissues and organs, including the brain, bone marrow, bloodstream, blood vessels, skeletal muscle, skin, and liver. These cells allow the person to repair damaged cells or produce new cells in a tissue or organ.
Today, adult stem cells are commonly used in patients who need bone marrow transplants. Scientists have been studying these cells in laboratories to determine if adult stem cells can be manipulated to produce specific types of cells. If scientists can find ways to make the adult stem cells produce specialized cells, they may be able to treat diseases. For instance, these specialized cells might be able to replace insulin-producing cells in patients with diabetes or dopamine-producing cells in patients with Parkinson's disease.
Embryonic stem cells are present in organisms during the very early stages of development. In an embryo that is three to five days old, these stem cells produce specialized cells that make up the heart, liver, lungs, and other tissues.
Scientists are capable of removing stem cells from a human embryo for research. They are removed from eggs that have been fertilized in a laboratory and then donated for research purposes. Scientists want to learn more about the functions of these cells and how they are different from specialized cells. Researchers have suggested that these cells may effectively cure diseases, such as multiple sclerosis (MS). These cells may be able to replace the dead or defective cells that cause such diseases.
Embryonic stem cell research is controversial. Some individuals believe it is unethical to isolate stem cells from an embryo because embryos have the potential to develop into human beings. They argue that adult stem cells from a variety of sources, including bone marrow, the placenta and umbilical-cord blood, have led to successful treatments for a number of diseases, making the destruction of human embryos unnecessary. Do No Harm: The Coalition of Americans for Research Ethics states that, "Stem cell research promises great good and is a worthy scientific priority as long as we pursue it ethically. Obtaining stem cells from people without seriously harming people in the process can be ethical. However, obtaining stem cells from human embryos cannot be ethical because it necessarily involves destroying those embryos."
In 2001, President George W. Bush approved federal funding for research of more than 60 pre-existing stem cell lines that have already been isolated from embryos. The embryos from which the existing stem cell lines were created had already been destroyed.
Federal funds are not available to isolate stem cells from additional embryos that have been fertilized in a laboratory and then donated for research purposes. Because the government does not currently support using embryos for research, it may only be conducted with private funds.
The umbilical cord, which carries blood, oxygen, and nutrients from the placenta to the baby during pregnancy, also contains stem cells. These cells can be removed from the placenta after the baby is born, and the umbilical cord is no longer needed.
Researchers are studying umbilical cord stem cells as possible treatments for diseases. One potential benefit of these cells is that they are less likely to cause transplant rejection than donated bone marrow or blood stem cells. Transplant rejection occurs when the transplant recipient recognizes the donated cells as foreign invaders and attacks them. Transplant rejection is less likely to occur because umbilical cord stem cells have not developed the features that the recipient's immune system can recognize and attack.
In addition, patients who receive umbilical cord blood have a decreased risk of developing graft-versus host disease (GVHD). This disease occurs when the donated cells attack the recipient's cells because they are identified as foreign. GVHD is less likely to occur because the umbilical cord blood does not contain well-developed immune cells needed to launch an attack.

Limitations

The results of the HGP have led to the development of more than 1,000 genetic tests for inherited human diseases and disorders. These tests are used to diagnose certain inherited medical conditions. They also allow patients to learn their risks of developing certain diseases. However, predictive genetic testing has sparked some debate because these tests only provide a probability for developing particular disorders. Even though many medical conditions have been linked to genetic causes, a person's biological makeup is not the only factor involved. Therefore, some people who carry a disease-associated mutation may never develop the disease. As a result, patients who test positive for a specific gene may become excessively worried about developing the disorder and experience a decreased quality of life.
Similarly, it is commonly believed that an individual's genetic makeup is just one factor, among many others, that influence behavior. An individual's environment, including social relationships and culture, has also been shown to influence behaviors. Therefore, if a person has just one gene associated with shyness, for instance, it does not necessarily mean that the person is going to be shy.

Future research

Researchers from HapMap are hopeful that they will find genetic factors for common inherited diseases that affect humans, including diabetes, heart disease, and mental illness, in the next few years.
A new initiative, called The Cancer Genome Atlas (TCG), aims to identify all of the genetic abnormalities that are associated with 50 of the most common types of cancer. The project, which began in 2006, is expected to take nine years to complete. Researchers plan to create a listing of all the mutations that cause cancer or allow cancerous growths to develop.
Newer, more effective drugs with fewer side effects are likely to be developed in the future for genetic disorders, such as Huntington's disease, cystic fibrosis, and Parkinson's disease. For instance, a new drug, called PTC124, has shown promising results as a treatment for cystic fibrosis and muscular dystrophy. This drug targets a specific type of mutation that can cause very different symptoms, depending on the particular gene that is mutated. Although this drug is still undergoing research to determine its safety and efficacy, researchers hope that it can help treat a wide range of inherited disorders.
In the future, patients may eventually have their individual genome analyzed for genes that are associated with specific diseases or disorders. As a result, preventative treatments and programs may be designed based on the patient's specific needs. However, preemptive screening may also lead to new ethical dilemmas. In order to prevent health insurance companies from denying coverage to people who have genes linked to specific conditions that are costly to treat, the U.S. senate passed a new bill in April 2008. The Genetic Information Nondiscrimination Act (GINA) is an amended version of H.R. 493, which passed the House April 25, 2007. The bill prohibits employers and health insurance companies from using the results of predictive genetic tests to discriminate against their workers or members.
In the future, it may be possible to alter the genes of an embryo for medical or non-medical reasons. For instance, individuals may ask scientists to manipulate the genes of an embryo to ensure that their child is a boy with blond hair and blue eyes. This type of gene manipulation would raise many ethical, religious, and social questions. Therefore, the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH) have set aside some of their budget to investigate the ethical, legal, and social issues (ELSI) regarding genetic research and its implications.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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