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Environmental Genome Project

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Related terms
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Related Terms
  • Disease, DNA, DNA sequencing, environment, gene, gene-environment interaction, knockout mouse, polymorphism, ribonucleic acid.

Background
  • The Environmental Genome Project is a large-scale investigation started in 1997 by the National Institute of Environmental Health Sciences, a U.S. government agency. Exposure to environmental factors, such as pollution, chemicals, or UV (ultraviolet) radiation from the sun, is known to increase the risk of developing some diseases, such as cancer. The goal of the project is to better understand how differences in genes among individuals cause some people to be more susceptible than others to diseases caused by environmental factors.
  • The DNA (deoxyribonucleic acid) of humans is stored in 23 pairs of chromosomes. Chromosomes contain hundreds of genes, which provide the instructions for making proteins in the body. Chromosomes also contain many other regulatory sequences that control how much of a gene will be made, when it will be made, and where in the body it will be made.
  • The DNA between any two humans is identical (more than 99%). However, the small amount of variation that remains in the DNA sequence is in part what leads to differences among individuals (e.g., some people being taller than others). Genetic variation also causes some people to be more susceptible to specific diseases than others. Genetic variation could result in altered gene function that may lead to disease, or it could result in a different physiological response to a drug or chemical.
  • To try to find these genetic differences, researchers are sequencing a select group of genes from an ethnically diverse group of people. DNA sequencing is a technique researchers use in order to determine the sequence of bases along a chromosome or in a gene. DNA contains four different chemical compounds called bases: cytosine, thymine, guanine, and adenine. In any given person, these bases are found in a particular order along the chromosomes. The order of these bases contains the information for making genes. Because specific genetic differences may be more common in some ethnic groups than in others, researchers believe they are more likely to find genetic differences in the "candidate genes" by sequencing the genes in individuals from different ethnic groups.
  • Researchers working on the Environmental Genome Project chose to study genes that they thought would likely respond to environmental factors. When researchers find a genetic difference in one of the genes they are studying, they may not immediately understand how the genetic difference affects gene function or human health. Researchers therefore often need to perform follow-up experiments in the lab to better understand how the genetic difference they found may lead to a difference in gene function and perhaps to disease development.
  • Ultimately, the Environmental Genome Project may help individuals who carry specific gene variants understand whether they are at increased risk for environmentally linked diseases. Individuals who are at increased risk may use this information to avoid environmental factors involved in causing the disease. Additionally, information from the Environmental Genome Project may help develop treatments for disease. By identifying which genes are involved in causing a disease, researchers may be able to develop therapies that target these genes to help prevent or treat the disease.

Methods
  • The aim of the Environmental Genome Project is to sequence genes to find genetic differences and then to study the functional consequences of those differences. Therefore, methods for gene sequencing and for studying gene function are important for this project.
  • Sequence genes: The first part of the Environmental Genome Project is sequencing a select group of genes from a selected group of people. Researchers chose 554 candidate genes to sequence as part of the Environmental Genome Project. In many cases, these particular genes were chosen because previous research indicated that they are involved in a cellular response to environmental factors. For example, some of the genes chosen include genes that control cellular growth, development, metabolism, or death. By sequencing these genes, researchers hoped to find the genetic differences involved in making some individuals more susceptible than others to diseases caused by environmental factors.
  • Researchers then chose to sequence these genes in a group of 90 ethnically diverse Americans, including individuals of European, African, Asian, and Mexican descent. Researchers believe they are more likely to find genetic differences in the candidate genes by sequencing them in individuals from different ethnic groups.
  • Genetic differences among individuals are sometimes referred to as polymorphisms. When researchers identified a polymorphism as a result of gene sequencing, they recorded the finding in a database. After the polymorphisms were collected in a database, they could then be studied in more detail in the lab. Researchers have already identified polymorphisms in some genes using these methods, and they continue to test additional genes.
  • Study polymorphism function: After researchers identify genetic differences, or polymorphisms, in the genes, they may study them more closely in the lab. Some polymorphisms may cause a gene to function in a different way, whereas others may have no effect on gene function. As part of the Environmental Genome Project, researchers hope to identify which polymorphisms cause a gene to function differently in response to environmental factors. Further, if a specific polymorphism causes a gene to function differently, researchers hope to determine if and why this change in function may make an individual more susceptible to environmentally linked diseases.
  • To study polymorphisms in the lab, researchers commonly use knockout mice. A knockout mouse is a genetically modified mouse with specific genes that are deactivated. Knockout mice can be used to study the function of a specific gene.
  • To create a knockout mouse, scientists either replace or deactivate an existing gene with a gene-targeting construct. Targeting constructs may contain "foreign" DNA from other organisms and are designed to contain sequences that are similar, or homologous, to the mouse DNA. There are several types of targeting constructs. Some insert a piece of foreign DNA into the gene, which interrupts the gene sequence. If designed properly, this interruption may inactivate the gene. Other targeting constructs are designed to replace a gene or critical gene sequence with foreign DNA. Some targeting constructs are designed so that an entire gene or a critical part of the gene is removed completely. Depending on the type of procedure used, the constructs may target either specific genes or random DNA sequences.
  • In the case of the Environmental Genome Project, researchers may produce a knockout mouse that contains a gene with a specific polymorphism. Researchers may then study this mouse in greater detail to determine whether that polymorphism has an affect on the mouse by exposing it to an environmental stimulus or chemical.

Research
  • Although the Environmental Genome Project is still in progress, researchers involved with the project have already begun to find links between the genes they are studying and disease.
  • PON1: Researchers have identified a genetic variant in the gene PON1,which may be involved in disease susceptibility. PON1 provides instructions for making an enzyme that helps the body break down toxic compounds called organophosphates. Organophosphates are present in many products, such as insecticides and solvents (liquids that can dissolve other substances). Using knockout mouse studies, researchers found that PON1 genes with a specific polymorphism were more effective at breaking down a type of toxic organophosphate. This research suggests that individuals who have this PON1 polymorphism are less at risk for being poisoned by some types of organophosphates.
  • NQO1: Researchers have identified a genetic variant in the gene NQO1, which may influence an individual's risk of developing leukemia, a cancer of the white blood cells. NQO1 provides instructions for making a protein called NAD(P)H:quinone acceptor oxidoreductase 1, which normally protects cells from damage that can be caused by chemicals called quinones. Quinones may be used for a variety of purposes, including manufacturing dyes or in photography. Researchers found that individuals who have a specific polymorphism in NQO1 have a slightly increased risk of developing leukemia. The researchers believe that individuals who have this polymorphism may have a significantly increased risk of developing leukemia if they are exposed to high levels of quinones.

Implications
  • Reduce human disease: The Environmental Genome Project may ultimately help reduce the incidence of some human diseases. If individuals know they have certain genetic polymorphisms (differences in genetic sequence) that may make them more susceptible to a specific disease, they could change their behavior to reduce the risk of developing that disease. For example, if an individual knows that he or she carries a polymorphism that makes him or her more susceptible to types of cancer caused by solar radiation, he or she could choose to reduce exposure to the sun.
  • Discrimination: Some polymorphisms are more prevalent in specific racial or ethnic groups. If certain disease-related polymorphisms are identified as being more prevalent in specific ethnic groups, members of those groups might be the subject of discrimination. For example, insurance companies may make it more difficult for individuals from a particular ethnic group to obtain insurance because they may have an increased risk of developing a certain disease. In addition, employers may be hesitant to hire an individual with a polymorphism that may make the individual more susceptible to developing a disease.
  • Medicine and drug development: Information from the Environmental Genome Project may help develop treatments for disease. By identifying which genes are involved in causing a disease, researchers may be able to develop targeted therapies to help prevent or treat the disease. Additionally, information from the Environmental Genome Project may help doctors decide which patients may benefit most from a treatment, an approach called personalized medicine. For example, patients with a particular polymorphism may be at increased risk of developing a specific disease and may therefore benefit more than someone else from receiving a certain treatment aimed at preventing the disease.

Limitations
  • Although the Environmental Genome Project has the potential to provide useful information regarding disease susceptibility on an individual level, it is a large-scale project. A large amount of DNA is being sequenced, and a large number of genes are being studied in the laboratory. Therefore, this is an expensive and time-consuming project, which requires the efforts of a large number of researchers.

Safety




Future research
  • The Environmental Genome Project is not yet completed. Researchers are still sequencing genes in an effort to identify more polymorphisms. Additionally, researchers are still investigating whether the polymorphisms they have identified influence the risk of human disease.
  • In the future, researchers hope that this work will uncover more genetic polymorphisms that are involved in disease development and deepen our understanding of how these polymorphisms lead to disease. Eventually, this understanding may lead to a reduction in some diseases through the development of new drugs or through the modification of individual behavior.

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

Bibliography
  1. Brower V. Looking for the trigger. The Environmental Genome Project to uncover the interactions of genes and the environment in disease. EMBO Rep. 2003 May;4(5):452-4.
  2. Environmental Health Perspectives. .
  3. Guengerich FP. The Environmental Genome Project: functional analysis of polymorphisms. Environ Health Perspect. 1998 Jul;106(7):365-8.
  4. National Institute of Environmental Health Sciences. .
  5. Natural Standard: The Authority on Integrative Medicine. .
  6. University of Washington NIEHS SNPS Program. .
  7. Teng CT, Gladwell W. Single nucleotide polymorphisms (SNPs) in human lactoferrin gene. Biochem Cell Biol. 2006 Jun;84(3):381-4.
  8. Wakefield J. Environmental genome project: focusing on differences to understand the whole. Environ Health Perspect. 2002 Dec;110(12):A757-9.
  9. Wilson SH, Olden K. The Environmental Genome Project: phase I and beyond. Mol Interv. 2004 Jun;4(3):147-56.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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