Genomics is the study of all of a person's genes (the genome), including interactions of those genes with each other and with the person's environment..
Deoxyribonucleic acid (DNA) is the chemical compound that contains the instructions needed to develop and direct the activities of nearly all living organisms. DNA molecules are made of two twisting, paired strands, often referred to as a double helix
Each DNA strand is made of four chemical units, called nucleotide bases, which comprise the genetic "alphabet." The bases are adenine (A), thymine (T), guanine (G), and cytosine (C). Bases on opposite strands pair specifically: an A always pairs with a T; a C always pairs with a G. The order of the As, Ts, Cs and Gs determines the meaning of the information encoded in that part of the DNA molecule just as the order of letters determines the meaning of a word.
Deoxyribonucleic acid (DNA) is the chemical compound that contains the instructions needed to develop and direct the activities of nearly all living organisms. DNA molecules are made of two twisting, paired strands, often referred to as a double helix
Each DNA strand is made of four chemical units, called nucleotide bases, which comprise the genetic "alphabet." The bases are adenine (A), thymine (T), guanine (G), and cytosine (C). Bases on opposite strands pair specifically: an A always pairs with a T; a C always pairs with a G. The order of the As, Ts, Cs and Gs determines the meaning of the information encoded in that part of the DNA molecule just as the order of letters determines the meaning of a word.
An organism's complete set of DNA is called its genome. Virtually every single cell in the body contains a complete copy of the approximately 3 billion DNA base pairs, or letters, that make up the human genome.
With its four-letter language, DNA contains the information needed to build the entire human body. A gene traditionally refers to the unit of DNA that carries the instructions for making a specific protein or set of proteins. Each of the estimated 20,000 to 25,000 genes in the human genome codes for an average of three proteins.
Located on 23 pairs of chromosomes packed into the nucleus of a human cell, genes direct the production of proteins with the assistance of enzymes and messenger molecules. Specifically, an enzyme copies the information in a gene's DNA into a molecule called messenger ribonucleic acid (mRNA). The mRNA travels out of the nucleus and into the cell's cytoplasm, where the mRNA is read by a tiny molecular machine called a ribosome, and the information is used to link together small molecules called amino acids in the right order to form a specific protein.
Proteins make up body structures like organs and tissue, as well as control chemical reactions and carry signals between cells. If a cell's DNA is mutated, an abnormal protein may be produced, which can disrupt the body's usual processes and lead to a disease such as cancer.
An organism's complete set of DNA is called its genome. Virtually every single cell in the body contains a complete copy of the approximately 3 billion DNA base pairs, or letters, that make up the human genome.
With its four-letter language, DNA contains the information needed to build the entire human body. A gene traditionally refers to the unit of DNA that carries the instructions for making a specific protein or set of proteins. Each of the estimated 20,000 to 25,000 genes in the human genome codes for an average of three proteins.
Located on 23 pairs of chromosomes packed into the nucleus of a human cell, genes direct the production of proteins with the assistance of enzymes and messenger molecules. Specifically, an enzyme copies the information in a gene's DNA into a molecule called messenger ribonucleic acid (mRNA). The mRNA travels out of the nucleus and into the cell's cytoplasm, where the mRNA is read by a tiny molecular machine called a ribosome, and the information is used to link together small molecules called amino acids in the right order to form a specific protein.
Proteins make up body structures like organs and tissue, as well as control chemical reactions and carry signals between cells. If a cell's DNA is mutated, an abnormal protein may be produced, which can disrupt the body's usual processes and lead to a disease such as cancer.
Sequencing simply means determining the exact order of the bases in a strand of DNA. Because bases exist as pairs, and the identity of one of the bases in the pair determines the other member of the pair, researchers do not have to report both bases of the pair.
In the most common type of sequencing used today, called sequencing by synthesis, DNA polymerase (the enzyme in cells that synthesizes DNA) is used to generate a new strand of DNA from a strand of interest. In the sequencing reaction, the enzyme incorporates into the new DNA strand individual nucleotides that have been chemically tagged with a fluorescent label. As this happens, the nucleotide is excited by a light source, and a fluorescent signal is emitted and detected. The signal is different depending on which of the four nucleotides was incorporated. This method can generate 'reads' of 125 nucleotides in a row and billions of reads at a time.
To assemble the sequence of all the bases in a large piece of DNA such as a gene, researchers need to read the sequence of overlapping segments. This allows the longer sequence to be assembled from shorter pieces, somewhat like putting together a linear jigsaw puzzle. In this process, each base has to be read not just once, but at least several times in the overlapping segments to ensure accuracy.
Researchers can use DNA sequencing to search for genetic variations and/or mutations that may play a role in the development or progression of a disease. The disease-causing change may be as small as the substitution, deletion, or addition of a single base pair or as large as a deletion of thousands of bases.
Sequencing simply means determining the exact order of the bases in a strand of DNA. Because bases exist as pairs, and the identity of one of the bases in the pair determines the other member of the pair, researchers do not have to report both bases of the pair.
In the most common type of sequencing used today, called sequencing by synthesis, DNA polymerase (the enzyme in cells that synthesizes DNA) is used to generate a new strand of DNA from a strand of interest. In the sequencing reaction, the enzyme incorporates into the new DNA strand individual nucleotides that have been chemically tagged with a fluorescent label. As this happens, the nucleotide is excited by a light source, and a fluorescent signal is emitted and detected. The signal is different depending on which of the four nucleotides was incorporated. This method can generate 'reads' of 125 nucleotides in a row and billions of reads at a time.
To assemble the sequence of all the bases in a large piece of DNA such as a gene, researchers need to read the sequence of overlapping segments. This allows the longer sequence to be assembled from shorter pieces, somewhat like putting together a linear jigsaw puzzle. In this process, each base has to be read not just once, but at least several times in the overlapping segments to ensure accuracy.
Researchers can use DNA sequencing to search for genetic variations and/or mutations that may play a role in the development or progression of a disease. The disease-causing change may be as small as the substitution, deletion, or addition of a single base pair or as large as a deletion of thousands of bases.
The Human Genome Project, which was led at the National Institutes of Health (NIH) by the National Human Genome Research Institute, produced a very high-quality version of the human genome sequence that is freely available in public databases. That international project was successfully completed in April 2003, under budget and more than two years ahead of schedule.
The sequence is not that of one person, but is a composite derived from several individuals. Therefore, it is a "representative" or generic sequence. To ensure anonymity of the DNA donors, more blood samples (nearly 100) were collected from volunteers than were used, and no names were attached to the samples that were analyzed. Thus, not even the donors knew whether their samples were actually used.
The Human Genome Project was designed to generate a resource that could be used for a broad range of biomedical studies. One such use is to look for the genetic variations that increase risk of specific diseases, such as cancer, or to look for the type of genetic mutations frequently seen in cancerous cells. More research can then be done to fully understand how the genome functions and to discover the genetic basis for health and disease.
The Human Genome Project, which was led at the National Institutes of Health (NIH) by the National Human Genome Research Institute, produced a very high-quality version of the human genome sequence that is freely available in public databases. That international project was successfully completed in April 2003, under budget and more than two years ahead of schedule.
The sequence is not that of one person, but is a composite derived from several individuals. Therefore, it is a "representative" or generic sequence. To ensure anonymity of the DNA donors, more blood samples (nearly 100) were collected from volunteers than were used, and no names were attached to the samples that were analyzed. Thus, not even the donors knew whether their samples were actually used.
The Human Genome Project was designed to generate a resource that could be used for a broad range of biomedical studies. One such use is to look for the genetic variations that increase risk of specific diseases, such as cancer, or to look for the type of genetic mutations frequently seen in cancerous cells. More research can then be done to fully understand how the genome functions and to discover the genetic basis for health and disease.
Source URL: http://www.genome.gov/18016863
Source Agency: National Human Genome Research Institute (NHGRI)
Captured Date: 2015-05-13 13:55:00.0
Frequently Asked Questions About Genetic Testing
- What is genetic testing?
- What can I learn from genetic testing?
- What are the different types of genetic tests?
- What are the benefits and drawbacks of genetic testing?
- How do I decide whether to be tested?
- Where can I find more information about genetic testing?
What is genetic testing?
Genetic testing uses laboratory methods to look at your genes, which are the DNA instructions you inherit from your mother and your father. Genetic tests may be used to identify increased risks of health problems, to choose treatments, or to assess responses to treatments.
What can I learn from testing?
There are many different types of genetic tests. Genetic tests can help to:
- Diagnose disease
- Identify gene changes that are responsible for an already diagnosed disease
- Determine the severity of a disease
- Guide doctors in deciding on the best medicine or treatment to use for certain individuals
- Identify gene changes that may increase the risk to develop a disease
- Identify gene changes that could be passed on to children
- Screen newborn babies for certain treatable conditions
Genetic test results can be hard to understand, however specialists like geneticists and genetic counselors can help explain what results might mean to you and your family. Because genetic testing tells you information about your DNA, which is shared with other family members, sometimes a genetic test result may have implications for blood relatives of the person who had testing.
What are the different types of genetic tests?
Diagnostic testing is used to precisely identify the disease that is making a person ill. The results of a diagnostic test may help you make choices about how to treat or manage your health.
Predictive and pre-symptomatic genetic tests are used to find gene changes that increase a person's likelihood of developing diseases. The results of these tests provide you with information about your risk of developing a specific disease. Such information may be useful in decisions about your lifestyle and healthcare.
Carrier testing is used to find people who "carry" a change in a gene that is linked to disease. Carriers may show no signs of the disease; however, they have the ability to pass on the gene change to their children, who may develop the disease or become carriers themselves. Some diseases require a gene change to be inherited from both parents for the disease to occur. This type of testing usually is offered to people who have a family history of a specific inherited disease or who belong to certain ethnic groups that have a higher risk of specific inherited diseases.
Prenatal testing is offered during pregnancy to help identify fetuses that have certain diseases.
Newborn screening is used to test babies one or two days after birth to find out if they have certain diseases known to cause problems with health and development.
Pharmacogenomic testing gives information about how certain medicines are processed by an individual's body. This type of testing can help your healthcare provider choose the medicines that work best with your genetic makeup.
Research genetic testing is used to learn more about the contributions of genes to health and to disease. Sometimes the results may not be directly helpful to participants, but they may benefit others by helping researchers expand their understanding of the human body, health, and disease.
What are the benefits and drawbacks of genetic testing?
Benefits: Genetic testing may be beneficial whether the test identifies a mutation or not. For some people, test results serve as a relief, eliminating some of the uncertainty surrounding their health. These results may also help doctors make recommendations for treatment or monitoring, and give people more information for making decisions about their and their family's health, allowing them to take steps to lower his/her chance of developing a disease. For example, as the result of such a finding, someone could be screened earlier and more frequently for the disease and/or could make changes to health habits like diet and exercise. Such a genetic test result can lower a person's feelings of uncertainty, and this information can also help people to make informed choices about their future, such as whether to have a baby.
Drawbacks: Genetic testing has a generally low risk of negatively impacting your physical health. However, it can be difficult financially or emotionally to find out your results.
Emotional: Learning that you or someone in your family has or is at risk for a disease can be scary. Some people can also feel guilty, angry, anxious, or depressed when they find out their results.
Financial: Genetic testing can cost anywhere from less than $100 to more than $2,000. Health insurance companies may cover part or all of the cost of testing.
Many people are worried about discrimination based on their genetic test results. In 2008, Congress enacted the Genetic Information Nondiscrimination Act (GINA) to protect people from discrimination by their health insurance provider or employer. GINA does not apply to long-term care, disability, or life insurance providers. (For more information about genetic discrimination and GINA, see http://www.genome.gov/10002328/genetic-discrimination-fact-sheet/).
Limitations of testing: Genetic testing cannot tell you everything about inherited diseases. For example, a positive result does not always mean you will develop a disease, and it is hard to predict how severe symptoms may be. Geneticists and genetic counselors can talk more specifically about what a particular test will or will not tell you, and can help you decide whether to undergo testing.
How do I decide whether to be tested?
There are many reasons that people might get genetic testing. Doctors might suggest a genetic test if patients or their families have certain patterns of disease. Genetic testing is voluntary and the decision about whether to have genetic testing is complex.
A geneticist or genetic counselor can help families think about the benefits and limitations of a particular genetic test. Genetic counselors help individuals and families understand the scientific, emotional, and ethical factors surrounding the decision to have genetic testing and how to deal with the results of those tests. (See: Frequently Asked Questions about Genetic Counseling)
Where can I find more information about genetic testing?
Talking Glossary of Genetic Terms
What You Need to Know about Direct-to-Consumer Genetic Testing 
Genetic Testing
From Genetics Home Reference: the benefits, costs, risks and limitations of genetic testing.
Genetic Testing Registry [ncbi.nlm.nih.gov]
A publicly funded medical genetics information resource developed for physicians, other healthcare providers, and researchers.
Prenatal Screening [marchofdimes.com]
Provides prenatal testing information, including ultrasound, amniocentesis and chorionic villus sampling (CVS).
National Newborn Screening & Genetics Resource Center [genes-r-us.uthscsa.edu]
Provides information and resources in the area of newborn screening and genetics.
Genetic Alliance- Genes in Life [genesinlife.org]
A guide from the Genetic Alliance with easy-to-read information about genetic testing.
Genetics and Cancer [cancer.gov]
An information fact sheet from the National Cancer Institute about genetic testing for hereditary cancers.
Find a Genetic Counselor [nsgc.org]
A search engine developed by the National Society of Genetic Counselors.
Last Updated: February 13, 2019
Source URL: http://www.genome.gov/19516567
Source Agency: National Human Genome Research Institute (NHGRI)
Captured Date: 2015-05-13 13:57:00.0
Frequently Asked Questions About Newborn Sequencing
- What is newborn screening?
- How does genomics come into it?
- Is the government planning to replace newborn screening with newborn genome sequencing?
- What about the emotional toll on families who receive information about mutations with health
consequences? - What protections are in place for families who do not wish to receive this information?
What is newborn screening?
Newborn screening in the United States is a major public health success that has saved countless lives. Each state runs its own newborn screening program, where almost all newborns are tested for at least 30 (and in some states more than 50) serious-but-treatable conditions that occur during childhood.
Almost all of the current newborn screening tests use a dried blood sample collected during the first week after birth to measure the presence of disease biomarkers (a measurable substance or characteristic that is indicative of a disease). Currently, the tests used by state newborn screening programs are fast, low cost and accurate in identifying disease before symptoms appear.
How does genomics come into it?
The cost of genome sequencing has now decreased to a price range similar to many other complex medical tests, increasing the possibilities for its clinical application. One potential use for genome sequencing would be to replace or supplement the existing traditional panels of newborn screening tests. Sequencing a newborn's genome could provide more health information than the current panel of tests, and could potentially be used to guide an individual's lifetime of medical care, providing early information on both treatable childhood diseases and conditions that occur in adulthood.
Many questions remain to be answered before contemplating a future of routine newborn genome sequencing. Among the questions are:
- Can DNA sequencing identify the same conditions at birth with as much accuracy and speed as traditional methods?
- Is having a genome sequence from birth useful for that individual's clinical care?
- What if the genome sequence reveals information about untreatable diseases, or even conditions that will not occur until adulthood?
- What is the risk to newborns that the identification of specific genetic variants, such as a predisposition to a disease, could lead to future discrimination?
- How might the use of genome sequencing affect public support for newborn screening programs?
- How feasible would it be for states to perform genome sequencing in addition, or instead of, existing testing programs?
- Are there additional considerations to collecting and storing newborn genome sequences versus newborn blood specimens?
Clinicians, scientists, bioethicists and others have debated these issues for several years but, until now, they have been abstract questions.
Thanks to a new research program being funded by the National Institutes of Health, a small number of pilot studies are beginning to carefully examine these questions. The program's goal is to generate scientific evidence and ethical considerations that healthcare professionals and policy makers can use to formulate future practical applications and policies related to the use of genome sequencing in the newborn period.Is the government planning to replace newborn screening with newborn genome sequencing?
No. This research effort seeks to determine whether or not genome sequence data could provide additional information that would be of benefit to newborns and their families during the newborn period.
What about the emotional toll on families who receive information about mutations with health consequences?
Studying the ethical, legal, and social implications of receiving genomic information about newborns is an integral component of this research program. While there have been discussions in the abstract about how families will process positive diagnoses, until now these issues have not been studied in depth. There is precedence for this approach. In the abstract, many experts believed that informing someone that they had an increased risk of developing Alzheimer's disease (which is untreatable) would cause severe psychological distress. Therefore, NIH funded the REVEAL and REVEAL II studies to explore whether these assumptions were true. Surprisingly, the results of those trials suggested that individuals are not unduly distressed, demonstrating the value of such research. It is important that we seek understanding of what, if any, impacts genome sequencing and similar information could have in this possible scenario.
What protections are in place for families who do not wish to receive this information?
Participation in NIH research is entirely voluntary. Participants will only be enrolled in the studies after participating in an informed consent process, where they will be educated about the goals of the study and the possible outcomes. While in some cases it may be possible to participate in a particular aspect of a study without receiving research results, one aim of the program is to determine how clinicians and families use genomic sequence information in decision-making. Several of the funded projects are specifically interested in how families understand and respond to genomic information (including optimal ways to communicate that information). Therefore participation in these research studies may not be suitable for families who do not wish to know what their sequence information contains. As with all federally funded biomedical research studies involving human research participants, the research is overseen by an Institutional Review Board at each institute, which monitors the study plans and implementation to ensure ethical conduct throughout the research process.
Last Updated: August 27, 2015
Source URL: http://www.genome.gov/27556918
Source Agency: National Human Genome Research Institute (NHGRI)
Captured Date: 2015-05-13 13:59:00.0
Genome-Wide Association Studies
- What is a genome-wide association study?
- Why are such studies possible now?
- How will genome-wide association studies benefit human health?
- What have genome-wide association studies found?
- How are genome-wide association studies conducted?
- How can researchers access data from genome-wide association studies?
- What is NIH doing to support genome-wide association studies?
What is a genome-wide association study?
A genome-wide association study is an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Once new genetic associations are identified, researchers can use the information to develop better strategies to detect, treat and prevent the disease. Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease and mental illnesses.
Why are such studies possible now?
With the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005, researchers now have a set of research tools that make it possible to find the genetic contributions to common diseases. The tools include computerized databases that contain the reference human genome sequence, a map of human genetic variation and a set of new technologies that can quickly and accurately analyze whole-genome samples for genetic variations that contribute to the onset of a disease.
How will genome-wide association studies benefit human health?
The impact on medical care from genome-wide association studies could potentially be substantial. Such research is laying the groundwork for the era of personalized medicine, in which the current one size-fits-all approach to medical care will give way to more customized strategies.
In the future, after improvements are made in the cost and efficiency of genome-wide scans and other innovative technologies, health professionals will be able to use such tools to provide patients with individualized information about their risks of developing certain diseases. The information will enable health professionals to tailor prevention programs to each person's unique genetic makeup. In addition, if a patient does become ill, the information can be used to select the treatments most likely to be effective and least likely to cause adverse reactions in that particular patient.
What have genome-wide association studies found?
Researchers already have reported considerable success using this new strategy. For example, in 2005, three independent studies found that a common form of blindness is associated with variation in the gene for complement factor H, which produces a protein involved in regulating inflammation. Few previously thought that inflammation might contribute so significantly to this type of blindness, which is called age-related macular degeneration.
Similar successes have been reported using genome-wide association studies to identify genetic variations that contribute to risk of type 2 diabetes, Parkinson's disease, heart disorders, obesity, Crohn's disease and prostate cancer, as well as genetic variations that influence response to anti-depressant medications.
How are genome-wide association studies conducted?
To carry out a genome-wide association study, researchers use two groups of participants: people with the disease being studied and similar people without the disease. Researchers obtain DNA from each participant, usually by drawing a blood sample or by rubbing a cotton swab along the inside of the mouth to harvest cells.
Each person's complete set of DNA, or genome, is then purified from the blood or cells, placed on tiny chips and scanned on automated laboratory machines. The machines quickly survey each participant's genome for strategically selected markers of genetic variation, which are called single nucleotide polymorphisms, or SNPs.
If certain genetic variations are found to be significantly more frequent in people with the disease compared to people without disease, the variations are said to be "associated" with the disease. The associated genetic variations can serve as powerful pointers to the region of the human genome where the disease-causing problem resides.
However, the associated variants themselves may not directly cause the disease. They may just be "tagging along" with the actual causal variants. For this reason, researchers often need to take additional steps, such as sequencing DNA base pairs in that particular region of the genome, to identify the exact genetic change involved in the disease.
How can researchers access data from genome-wide association studies?
The National Center for Biotechnology Information (NCBI), a part of NIH's National Library of Medicine, is developing databases for use by the research community. An archive of data from genome-wide association studies on a variety of diseases and conditions already can be accessed through an NCBI Web site, called the Database of Genotype and Phenotype (dbGaP) located at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap.
What is NIH doing to support genome-wide association studies?
NIH, the Foundation for the National Institutes of Health, Pfizer Global Research & Development and others have formed a public-private partnership, the Genetic Association Information Network (GAIN), to fund genome-wide association studies. After peer-review of applications, GAIN announced its first round of studies in October 2006. The initial studies include bipolar disorder, major depression, kidney disease in type 1 diabetes, attention deficit hyperactivity disorder, schizophrenia and psoriasis. More information about GAIN can be found at: http://www.fnih.org/work/past-programs/genetic-association-information-network-gain.
In addition, individual NIH institutes have started genome-wide association studies. For example, the National Heart Lung and Blood Institute (NLBI) has launched the Framingham Genetic Research Study in collaboration with the Boston University School of Medicine. In that study, 9,000 participants in the long-running Framingham Heart Study will undergo genome-wide association studies to identify the genes underlying cardiovascular and other chronic diseases, such as osteoporosis and diabetes. More information on that study can be found at: http://www.nhlbi.nih.gov/news/press-releases/2006/nhlbi-to-launch-framingham-genetic-research-study.html.
Other NHLBI efforts in this area include genome-wide association studies involving the Women's Health Study, the Women's Health Initiative and the Candidate Gene Association Resource, which pools DNA samples collected from multiple NHLBI cohort studies. NHLBI, along with the National Institute of General Medical Sciences, also are major contributors to the PharmacoGenetics Research Network. Along with many other tools and technologies, this network is using genome-wide association studies to explore the effects of genes on individuals' varying responses to medications.
Some NIH institutes already have completed genome-wide association studies and deposited their data in the NCBI dbGaP database. These studies include research by the National Eye Institute on age-related eye diseases and the National Institute of Neurological Disorders and Stroke on Parkinson's disease.
Last Updated: August 27, 2015
Source URL: http://www.genome.gov/20019523
Source Agency: National Human Genome Research Institute (NHGRI)
Captured Date: 2015-05-13 13:57:00.0
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