Genomic Research

Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being. The next stage of genomic research will begin to derive meaningful knowledge from the DNA sequence. Research studies that build on the work of the Human Genome Project are under way worldwide.

The objectives of continued genomic research include the following:

• Determine the function of genes and the elements that regulate genes throughout the genome.

• Find variations in the DNA sequence among people and determine their significance. The most common type of genetic variation is known as a single nucleotide polymorphism or SNP (pronounced “snip”).  These small differences may help predict a person’s risk of particular diseases and response to certain medications.

• Discover the 3-dimensional structures of proteins and identify their functions.

• Explore how DNA and proteins interact with one another and with the environment to create complex living systems.

• Develop and apply genome-based strategies for the early detection, diagnosis, and treatment of disease.

• Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.

• Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.

• Continue to explore the ethical, legal, and social issues raised by genomic research.

For more information about the genomic research following the Human Genome Project:

The National Human Genome Research Institute supports research in many of the areas described above. The Institute provides detailed information about its research initiatives at NIH and nationwide. In addition, the NIH Roadmap outlines major initiatives in biomedical research.

A fact sheet titled Genes—What We Knew, Know, and Hope to Learn provides an outline of progress in genomic research from the National Institute of General Medical Sciences.

The U.S. Department of Energy Office of Science provides information about its genomics programs at genomics.energy.gov. A look at the possible benefits and applications of future research can be found in the article Fast Forward to 2020: What to Expect in Molecular Medicine. Additionally, the Office of Science offers a timeline of research events during and since the Human Genome Project.

Single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.

SNPs occur normally throughout a person’s DNA. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. They can act as biological markers, helping scientists locate genes that are associated with disease. When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function.

Most SNPs have no effect on health or development. Some of these genetic differences, however, have proven to be very important in the study of human health. Researchers have found SNPs that may help predict an individual’s response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases. SNPs can also be used to track the inheritance of disease genes within families. Future studies will work to identify SNPs associated with complex diseases such as heart disease, diabetes, and cancer.

For more information about SNPs:

An audio definition of SNPs is available from the National Human Genome Research Institute’s Talking Glossary of Genetic Terms.

The NCBI Science Primer offers a detailed description of SNPs in the chapter titled SNPs: Variations on a Theme.

The U.S. Department of Energy Office of Science provides additional information in its SNP Fact Sheet.

A detailed overview of SNPs and their association with cancer risk can be found in the National Cancer Institute’s Understanding Cancer Series: Genetic Variation (SNPs).

For people interested in more technical data, several databases of known SNPs are available:

• NCBI database of single nucleotide polymorphisms (dbSNP)

• Database of Japanese single nucleotide polymorphisms (JSNP)

Genome-wide association studies are a relatively new way for scientists to identify genes involved in human disease. This method searches the genome for small variations, called single nucleotide polymorphisms or SNPs (pronounced “snips”), that occur more frequently in people with a particular disease than in people without the disease. Each study can look at hundreds or thousands of SNPs at the same time. Researchers use data from this type of study to pinpoint genes that may contribute to a person’s risk of developing a certain disease.

Because genome-wide association studies examine SNPs across the genome, they represent a promising way to study complex, common diseases in which many genetic variations contribute to a person’s risk. This approach has already identified SNPs related to several complex conditions including diabetes, heart abnormalities, Parkinson disease, and Crohn disease. Researchers hope that future genome-wide association studies will identify more SNPs associated with chronic diseases, as well as variations that affect a person’s response to certain drugs and influence interactions between a person’s genes and the environment.

For more information about genome-wide association studies:

The National Human Genome Research Institute provides a detailed explanation of genome-wide association studies.

For people interested in more technical information, the NCBI’s Database of Genotype and Phenotype (dbGaP) contains data from genome-wide association studies. An introduction to this database, as well as information about study results, is available from the dbGaP press release. In addition, the National Human Genome Research Institute provides a Catalog of Published Genome-Wide Association Studies.

The International HapMap Project is an international scientific effort to identify common genetic variations among people. This project represents a collaboration of scientists from public and private organizations in six countries. Data from the project is freely available to researchers worldwide. Researchers can use the data to learn more about the relationship between genetic differences and human disease.

The HapMap (short for “haplotype map”) is a catalog of common genetic variants called single nucleotide polymorphisms or SNPs (pronounced “snips”).  Each SNP represents a difference in a single DNA building block, called a nucleotide.  These variations occur normally throughout a person’s DNA. When several SNPs cluster together on a chromosome, they are inherited as a block known as a haplotype.  The HapMap describes haplotypes, including their locations in the genome and how common they are in different populations throughout the world.    

The human genome contains roughly 10 million SNPs. It would be difficult, time-consuming, and expensive to look at each of these changes and determine whether it plays a role in human disease. Using haplotypes, researchers can sample a selection of these variants instead of studying each one. The HapMap will make carrying out large-scale studies of SNPs and human disease (called genome-wide association studies) cheaper, faster, and less complicated.

The main goal of the International HapMap Project is to describe common patterns of human genetic variation that are involved in human health and disease. Additionally, data from the project will help researchers find genetic differences that can help predict an individual’s response to particular medicines or environmental factors (such as toxins.)

For more information about the International HapMap Project:

The National Human Genome Research Institute provides an overview of the project in their International HapMap Project fact sheet. The fact sheet also includes a link to a more in-depth online tutorial on HapMap usage.

Detailed information about the project, as well as project data, are available from the International HapMap Project web site.

Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup.

Many drugs that are currently available are “one size fits all,” but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions.

The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.

For more information about pharmacogenomics:

The U.S Department of Energy Office of Science offers a fact sheet on pharmacogenomics. This resource outlines the anticipated benefits of this approach and lists barriers to progress.

Basic information about pharmacogenomics is also available from the Wellcome Trust. Additionally, the Wellcome Trust offers an article about the ethical considerations surrounding pharmacogenomics.

The National Institute of General Medical Sciences offers a list of Frequently Asked Questions about Pharmacogenomics.

The National Center for Biotechnology Information provides a discussion of this topic as part of its Science Primer: One Size Does Not Fit All: The Promise of Pharmacogenomics.

Additional information about pharmacogenetics is available from the Centre for Genetics Education.

The Genetic Science Learning Center at the University of Utah offers an interactive introduction to pharmacogenomics.

Genetic Tools offers a teaching case about genetic testing that predicts drug response (pharmacogenetic testing).

A list of clinical trials involving pharmacogenomics is available from ClinicalTrials.gov, a service of the National Institutes of Health.