Large-Scale Genome Sequencing Program

Related Terms

HapMap Project, heredity, HGP, Human Genome Project, knockout mouse, Knockout Mouse Project, KOMP, Large-Scale Genome Sequencing Program, overview of genomics, TCGA, The Cancer Genome Atlas Group, The ENCODE Project.

Background

Genetics is the scientific study of how specific traits and physical characteristics are passed down from parents to their children. This is also known as heredity. All of the genes in a single organism are called the genome. Genes are considered the building blocks of life because they provide instructions for all of the cells in the body. The study of an organism's genome is called genomics.
All people have about 99.9% of the same genetic information. The differences in the remaining 0.1% may provide information about the causes and epidemiology of many diseases. This is because many illnesses have been linked to mutations in specific genes. Researchers are studying genomics to help prevent, diagnose, treat, and possibly cure inherited disorders.
In addition to diseases, the human genome provides information about physical characteristics, personality, and behavior. Scientists continue to debate whether the environment or genetics is the primary cause of an individual's behavior, personality, or some types of physical traits (such as obesity). Although most researchers believe it is a combination of these two elements that leads to the development of such characteristics, experts disagree over which has a greater impact on an individual. Research in genomics may help scientists learn more about the impact of a person's genetic makeup.
Some researchers are studying the genomics of animals, such as the mouse. Scientists often study mice because mice and humans share about 85% of their genes. Therefore, many (but not all) of the discoveries made in mice are applicable to humans. In addition, much of the research done in mice would be unethical or impossible in humans. Therefore, using mice can help researchers learn more about the safety of certain procedures before trying them in humans.

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. The goal was to determine where genes are located in specific chromosomes.
Researchers from the United States, China, France, Germany, 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 hope that understanding the human genome will help them understand the causes and epidemiology of diseases. As a result, research in this area may lead to new strategies to diagnose, treat, and prevent inherited disorders, such as Down's 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 each of the cells of every 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. Maps of each chromosome are made by determining how frequently two markers are passed together from a parent to a child. These maps describe the tendency of genes to be inherited together as a result of their location on the same chromosome.

Research

General: There are hundreds of national, international, and privately-funded organizations that are studying genomics. Below are some of the most well-known organizations.
HapMap Project: 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 genes that are related to conditions, such as obesity and age-related blindness.
The Cancer Genome Atlas (TCGA): A new initiative, called The Cancer Genome Atlas (TCGA), aims to identify all of the genetic abnormalities that are associated with 50 of the most common types of cancer. Eligible cancer patients donate small tissue samples, and the researchers use a variety of technologies to analyze and record the genetic material in the samples. The project, which began in 2006, is expected to take nine years to complete. Researchers plan to create a list of all the mutations that cause cancer or allow cancerous growths to develop.
The ENCODE project: The Encyclopedia of DNA Elements, also called The ENCODE Project, was launched in 2003 to identify all of the functional elements in the human genome. Funded by the National Human Genome Research Institute (NHGRI), The ENCODE Project is being conducted in three stages: a pilot project phase, a technology development phase, and a planned production phase.
The first two phases are currently underway. Scientists from a diverse range of backgrounds are testing and comparing existing methods to analyze part of the human genome. During the technology phase, researchers aim to develop new and better methods to achieve this goal and efficiently analyze the entire genome, not just a part of it. All data that The ENCODE Project produces will be available on public databases.
The Large-Scale Genome Sequencing Program: Several research programs are involved in the Large-Scale Genome Sequencing Program, which is a national program that is funded by the National Human Genome Research Institute (NHGRI).
The program aims to generate gene sequencing information. It is divided into five major areas of interest: medical sequencing, survey of human structural variation, pathogens and vectors, annotating the human genome, and comparative genome evolution. Scientists who study medical sequencing aim to learn about the genomic variations that cause human disorders. The survey of human structural variation aims to use the sequenced genome to characterize large genetic structural variants in human populations. Researchers studying pathogens and vectors use basic sequence information to learn more about important disease-causing microorganisms (called pathogens). Scientists who are annotating the human genome use comparative sequence information to identify the functional elements of the human genome. Those who study the comparative genome evolution use comparative sequence information to learn more about the origin and evolution of genes, as well as their functions in relation to human diseases.
Knockout Mouse Project (KOMP): A knockout mouse is a type of laboratory mouse that is used for genetic research. When a scientist deactivates, or knocks out, a specific type of gene, the animal is called a knockout mouse. The Knockout Mouse Project (KOMP) is a trans-National Institutes of Health (NIH) initiative that aims to inactivate each of the 200,000 protein-coding genes in mice, one at a time.
During a knockout study, scientists insert an artificial piece of DNA to either replace or deactivate an existing gene inside a mouse embryo. Depending on the type of procedure used, the artificial gene may either target a specific gene or randomly replace or deactivate one of the mouse's genes.
When a gene is knocked out, the mouse's physical and/or biochemical characteristics (called phenotype), are changed. This is because the mouse's genetic makeup has been slightly altered.
This type of research allows scientists to learn what specific genes do. Whatever characteristic changes after a gene is replaced or deactivated indicates the function of the knocked out gene.
Research with knockout mice also provides information on how some inherited disorders and diseases work. Using knockout studies, researchers have learned about genes that are associated with many different diseases, including cystic fibrosis, obesity, heart disease, arthritis, blindness, Parkinson's disease, muscular dystrophy, aging, and various types of cancer. Understanding the pathology of these diseases is important because it ultimately helps researchers develop new treatments and possible ways to prevent certain illnesses.

Implications

General: The completed human genome is similar to having an instructional map on how the human body grows and functions. 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.
Information about 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.
Diagnosing human diseases: 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.
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.
It is important to note that genetic tests only provide a probability for developing a particular disorder. This is because genetic disorders are believed to be caused by a combination of genetic and environmental factors. Some people who carry a disease-associated mutation may never develop the disease.
Treating human diseases: The biomedical technology industry has also benefited from the completed human genome. Since the human genome was completed, many new technologies and medical treatments that use living cells and/or biological molecules have been designed. Currently, at least 350 biotechnology-based products are undergoing clinical trials. Patients should keep in mind that it 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).
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.
Scientists are also researching the effects of genetics on a person's ability to break down, absorb, and excrete drugs, herbs, and supplements. Some individuals are highly susceptible to side effects of certain medications. Research in this area may help individuals choose safer and more effective treatment options for patients with inherited disorders.
In addition, an experimental procedure called gene therapy may help treat or prevent inherited disorders and some types of cancer. Gene therapy involves inserting human genes into a patient in order to treat or prevent an illness. Researchers hope that gene therapy can be used instead of medications or surgery to treat or prevent inherited disorders that are currently incurable. Scientists also hope that gene therapy can prevent the growth of cancerous tumors and help kill cancer that has already developed.
Because the safety of gene therapy remains unknown, it is only being studied for the treatment of diseases that have no known cures, such as Parkinson's disease and Huntington's disease. No gene therapy products that introduce genetic material into the body have been approved for sale in the United States. Currently, gene therapy is only available through clinical trials. Gene therapy is a growing area of research, and hundreds of trials are ongoing.
Stem cell research: Researchers are also interested in studying stem cells, which 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 be an effective cure for 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.
Preventing human diseases: It is possible that by identifying disease-associated genes, scientists may be able to prevent certain disorders from occurring. For instance, if a person has a family history of a particular disorder, a scientist may one day be able to remove the mutated gene from an egg, sperm, or embryo. Once the gene is removed, the embryo could be inserted into the woman's uterus, and she would give birth to a healthy baby.
Changing a person's biological makeup: 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. Some individuals do not believe an embryo should be changed at all before conception, even for medical reasons. Others might argue that altering a gene for non-medical reasons is unnecessary and may limit social diversity.

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.
Studies are being performed to develop newer, more effective drugs with fewer side effects for genetic disorders, such as Huntington's disease, cystic fibrosis, and Parkinson's disease. As research continues in this area, other medical treatments, such as gene therapy, may prove to be effective therapies for genetic disorders.
Researchers are also interested in studying stem cells, which 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).
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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