GenRISK Adult Genetics Program Testing

Genetics 101

Genetics and genetic testing are complicated subjects. The following will give you an overview. You may want to explore other websites as well. The National Institute of Health's publication, "Understanding Gene Testing"  is a good resource.

The National Human Genome Research Institute has a useful glossary of genetic terms  with pictures. During your GenRISK appointment, we will explain genetic concepts in more detail and answer your questions. Below is a brief lesson in "Genetics 101."

Our bodies consist of millions and millions of cells. Genetic material, or DNA, is stored inside each. The DNA is organized into 46 packages, called chromosomes. Genes are simply pieces of information carried on the chromosomes. Cells use genes like instructions to make proteins they need to function. Human beings are thought to have 30,000 to 35,000 genes, divided among the chromosomes in each cell. The DNA that genes are made of is like a code written with only four letters. Sometimes misspellings (mutations) happen in a gene. Extra letters may be inserted into the code. Letters may be missing. Or one letter is found where another ought to be. Sometimes, but not always, these mutations can cause disease.

Most of our chromosomes come in pairs, like the genes they carry. One copy of each gene comes from our mother and one from our father. Some genetic diseases are caused when there is a mutation in both copies of a gene. These are called "recessive" conditions. Cystic fibrosis and sickle cell anemia are examples of recessive diseases. Other genetic diseases occur when there is a mutation in only one copy of a gene. These diseases are "dominant" conditions. Marfan syndrome and most hereditary cancer syndromes are dominant conditions. Some genetic diseases are much more complex. They are caused by the combination of more than one gene mutation and the environment. Cardiovascular disease, asthma and most common cancers are examples of complex genetic diseases.

Genetic tests identify genetic mutations or the signs that a mutation may be present. Some genetic tests involve checking a gene's DNA code "letter by letter" to find a mutation directly. When this isn't practical, less direct methods are used. For example, genetic tests may look at the proteins made by a gene to see if they are normal in size or other characteristics. Some genetic tests look at the bigger picture. Such biochemical tests look at the role of the enzymes and proteins that are encoded by our genes. Several tests done for genetic risk of heart disease are biochemical tests.

Selecting Tests and Laboratories

Even with the success of the Human Genome Project, there still isn't a genetic test for every disease. A disease may run in a family and clearly be inherited, but the gene responsible may not be identified yet. The GenRISK team will see if there is a genetic test available for the condition running in your family.

If a test exists, the GenRISK team will find the best laboratory to use. Some laboratories offer clinical testing and must follow federal quality control standards. The government set standards for laboratories in the Clinical Laboratory Improvement Act (CLIA) of 1993. CLIA laboratories typically quote a fixed price and a standard return time for results.

Other laboratories offer research testing and are usually linked to academic centers and universities. They do testing at no cost in most cases. However, often research laboratories do not provide results. If they do, it may take months or years to deliver results. Research test results should be confirmed in a clinical laboratory if medical management is based on the result.

Testing Strategies

Not everyone who has a genetic disease will have a mutation or a biochemical abnormality that shows up in testing. Because of this limitation, in a family it makes sense to first test someone who has had the disease in question.

If a genetic risk factor is found, ways of managing or preventing the disease due to that genetic risk can be discussed. Additionally, at-risk relatives can check their own status by testing for that specific risk factor. If that specific genetic risk factor is not found in an at-risk relative (i.e., they have a normal test result), he or she can be reassured. If the at-risk relative has a positive genetic test result, he or she has a greater chance of getting the condition. Relatives whose risk has been confirmed can start screening and prevention practices targeted for their genetic risk.

Sometimes testing a family member who has the disease is not possible. (The person may be dead, unavailable or unwilling to be tested.) An unaffected person can take the test but only if indicated. Finding a genetic risk factor will certainly give useful information, but a normal test result does not always mean there is no risk. Many genes responsible for an inherited susceptibility are not yet known. In other words, a normal test result can exclude the genetic risk factors that have been tested but not the possibility of an inherited susceptibility. It may be valuable to test other family members.

If you were to have genetic testing it would be important to interpret your test results in light of your personal and family medical history. We will also identify family members who might benefit from risk assessment and genetic testing. If necessary, we can provide referrals for relatives outside the Los Angeles area.

Practical Issues

Genetic tests are typically DNA-based or biochemical. DNA-based testing is often done to identify an inherited risk of cancer. Biochemical testing is often done when evaluating the risk of cardiovascular disease or diabetes. DNA-based tests are usually done on DNA from a blood sample. Sometimes DNA tests can be done on stored pathology samples, such as tumor tissue from a past surgery of a family member who has died.

Most commercial laboratories use PCR-based (polymerase chain reaction) methods to amplify a DNA sample. This is followed by sequencing or other testing methods. Sequencing is the gold standard for genetic testing in most cases. However, even sequencing may miss rearrangements or large deletions of DNA or mutations in regulatory regions. Much more rarely, errors can happen if samples are handled incorrectly, there is contamination in the lab or the PCR technique fails.

Testing costs and turnaround times vary. Genetic test results are usually ready in three to four weeks. Though genetic testing costs are often paid for by insurance carriers, patients may be required to pay some or all of the cost when the test is ordered. Under certain circumstances, once you have attended our clinic, our staff will write a letter of medical necessity explaining the benefits genetic testing might have for you. This can often increase the likelihood that your insurance company will pay for the testing.

Potential Benefits of Testing

If you test negative for a genetic risk factor that is known to run in your family you may be relieved that a major risk factor has been excluded since your risk for disease will not be increased. If you test positive for a genetic susceptibility, you may want to start screening earlier or more often. Preventive actions may be useful as well. Preventive surgery may reduce the risk of a disease. Drugs, diet and lifestyle changes may help prevent the disease improve treatment. If you test positive for a genetic susceptibility, close relatives might value having this information and going through testing themselves to determine their disease risks and the best preventive approach.

Potential Risks and Limitations of Testing

Finding a genetic susceptibility only shows there is a higher risk of developing a specific disease, but it does not tell us if or when the disease will develop. Although DNA-based genetic testing is very accurate, there is a chance that an inherited mutation will be missed. If a mutation is not found, the test results cannot exclude the possibility of an inherited risk since there may be a mutation in another gene for which testing was not done. An inherited disease risk can only be excluded if a known mutation in the family has been excluded. Even if a genetic test shows that a person does not have the mutation that causes susceptibility to a disease running in the family, it doesn't mean he or she will never get the disease. It means only that the risk is reduced and probably similar to the average person's risk.

Family relationships may be affected by this information. If you have a genetic susceptibility, other family members might benefit by also knowing. In the process of sharing your genetic risk information, family members may learn things about you that you do not want known. In addition, you may learn things about relatives that you did not want to know. For example, it may be revealed that a family member is adopted.

Some people find it hard to learn that they carry a gene that makes their risk of developing a disease greater. They may feel many emotions, including anger, fear about the future, anxiety about their health or guilt about passing a mutation on to their children. They may be shocked by the news. They may go through denial or a change in their self-image.

Sometimes genetic test results are uninformative or ambiguous, making it difficult or impossible to say if a person has a higher risk. These ambiguous results can be the most difficult as they don't provide a clear-cut answer.

For people with normal test results, where the genetic risk in the family has been excluded, a variety of emotions might occur. Most people feel tremendous relief. Others may feel survivor guilt, wondering why they were spared the risk. This can sometimes lead to changes in relationships between family members.

Potential for Genetic Discrimination

Knowing that you have a higher risk of getting a particular disease may affect your ability to be insured (health, life and disability). Several state and federal laws prohibit use of genetic information by health insurance companies. California has enacted some of the toughest anti-genetic discrimination legislation, and currently at the federal level, there are laws being debated in the Congress that would outlaw genetic discrimination for those with a predisposition to disease. In general, health insurers cannot use this information as a preexisting condition that could disqualify you when applying for new insurance. Genetic information cannot be used to raise premium payments or to deny coverage. However, these laws are not fully comprehensive and may not entirely prevent discrimination. You may want to contact your insurance company to see what effect, if any, genetic testing may have on your coverage. For more information about the laws enacted in California and HIPAA (federal legislation), please visit our Insurance Coverage  page or contact the Cancer Legal Resource Center, a joint program of the Western Law Center for Disability Rights and Loyola Law School, at (213) 736-1455.

Android app on Google Play