Purpose of Test
Your healthcare provider may order a genetic test for any number of reasons related to diagnosis, prevention, and treatment. Genetic testing can also be used in legal investigations. There are even direct-to-consumer tests able to trace your ancestry.
How Genetic Tests Work
Nearly every cell in your body contains DNA, genes, and chromosomes. Each serves a specific and interrelated function:
DNA (deoxyribonucleic acid) is a double-stranded molecule that contains all the genetic information about you as an individual. DNA is made up of four substances known as adenine (A), thymine (T), cytosine (C), and guanine (G). The unique sequence of these substances provides the “programming code” for your body. A gene is a distinct portion of DNA that contains the coded instructions on how and when to build specific proteins. While a gene is meant to perform in a standard way, any flaws in its DNA coding can affect how those instructions are delivered. These flaws are referred to as genetic mutations. A chromosome is a bundled unit of genes. Every human has 46 genes, 23 of which are inherited from the mother and father, respectively. Each chromosome contains between 20,000 to 25,000 genes.
Since the early 1900s, scientists have understood that specific genetic variations (genotypes) translate into specific physical characteristics (phenotypes). In recent years, advances in technology and a broader understanding of the human genome have allowed scientists to pinpoint which mutations confer to certain illnesses or characteristics.
Types of Genetic Tests
Genetic tests have far-ranging applications in medical and non-medical settings. They include:
Diagnostic testing to confirm or rule out a genetic disorder Carrier testing done prior to or during pregnancy to see if you and your partner carry a gene that may cause a congenital defect Prenatal diagnosis to detect abnormalities in a fetus’s genes before birth to identify congenital disorders or birth defects Newborn screening to routinely screen for 21 inheritable disorders, as mandated by law Preimplantation testing used to screen embryos for abnormalities as part of the in vitro fertilization (IVF) process Predictive diagnosis to estimate your risk (predisposition) of developing a genetically influenced disease, like breast cancer, later in life Pharmacogenetics testing to determine whether your genetics may influence your response to drug therapies, particularly genetic resistance to viruses such as HIV
Non-medical uses of genetic testing include paternity test (used to identify inheritance patterns between individuals), genealogy testing (to determine ancestry or heritage), or forensic testing (to identify an individual for legal purposes).
Currently Available Tests
The number of genetic tests available to diagnose disease is increasing each year. In some cases, the tests may be more suggestive than diagnostic given that understanding about disease genetics (such as with cancer and autoimmune disorders) remains limited.
Among some of the genetic tests currently used for diagnosis:
Becker/Duchenne associated with muscular dystrophy BRCA1 and BRCA2 mutations associated with breast, ovarian, and prostate cancers Cell-free DNA screening used to diagnose Down syndrome CTFR mutations associated with cystic fibrosis FH mutations associated with familial hypercholesterolemia FMR1 mutations linked to autism and intellectual disability HD mutations associated with Huntington’s disease HEXA mutations associated with Tay-Sachs disease HBB mutations associated with sickle cell anemia IBD1 mutations linked to inflammatory bowel disease (IBD) LCT mutations associated with lactose intolerance MEN2A and MEN2B mutations associated with thyroid cancer NOD2 mutations associated with Crohn’s disease PAI-1 mutations, predictive of coronary artery disease (CAD) and stroke
There are today well over 2,000 genetic tests available for medical and non-medical purposes, according to the Bethesda, Maryland-based National Human Genome Research Institute.
Risks and Contraindications
The physical risks of genetic testing are small. Most require a blood or saliva sample or a swab of the inside of your cheek (known as a buccal smear). Depending on the aims of the test, it may only require a few drops of blood (such as for newborn screening or paternity testing) or several vials (for cancer or HIV testing).
If cancer is suspected, a biopsy may be performed to obtain cells from a solid tumor or bone marrow. The risks of biopsy can vary depending on how invasive the procedure is, ranging from localized pain and bruising to scarring and infection.
Prenatal Risks
Prenatal genetic testing is commonly performed on maternal blood. One example is the cell-free fetal DNA (cfDNA) test performed after the 10th week of pregnancy. The risks to the mother and baby are no greater than that for a blood draw done on a non-pregnant individual.
Genetic testing can also be performed on amniotic fluid obtained through amniocentesis. Amniocentesis can be used to perform a karyotype, which screens for genetic disorders such as Down syndrome, cystic fibrosis, and neural tube defects like spina bifida. Side effects may include cramping, localized pain at the puncture site, and accidental bladder perforation. Amniocentesis carries a one-in-400 risk of miscarriage.
By contrast, samples obtained through chorionic villus sampling (CVS) may result in pregnancy loss in one of every 100 procedures. CVS can be used to screen for the same congenital conditions with the exception of neural tube defects. It is not recommended for women with an active infection, who are expecting twins, or who are experiencing vaginal bleeding, among others. Side effects may include spotting, cramping, or infection.
Considerations
Beyond the physical risks of testing, ethicists remain concerned about the emotional impact of learning that you may or may not develop a serious illness years or even decades from now. The uncertainty can cause stress about your future and/or your ability to obtain health or life insurance when needed.
Efforts are being made to address some of these concerns. In 2009, the Genetic Information Non-Discrimination Act (GINA) was passed by the U.S. Congress, banning discrimination in health insurance or employment based on the results of a genetic test. Despite efforts to broaden protection, GINA does not apply to companies with less than 15 employees or prevent discriminatory practices among life insurance providers.
If considering an elective test, it is important to meet with a trained genetic counselor to fully understand the benefits, risks, and limitations of testing. This includes your “right not to know” if any unintended findings are uncovered.
In some cases, knowing you have a genetic predisposition for a disease like breast cancer can help you make important decisions about your health. At other times, knowing about a disease that may or may not develop, and for which there may be no treatment, may not be something you want to face. There is no wrong or right answer in either regard; there is only personal choice.
Before the Test
A genetic test does not require much preparation on your part. The only exception may be prenatal tests, which sometimes require food and/or fluid restrictions.
Timing
Depending on the purpose of the investigation, a genetic test may take as little as a few minutes to perform.
With the exception of direct-to-consumer ancestry kits, most genetic tests will involve some level of pre-test counseling. Even if your healthcare provider orders the test as part of an ongoing investigation, expect to spend no less than 15 minutes at the lab or clinic (not including the wait time).
Prenatal tests may take anywhere from 30 to 90 minutes to perform, depending on whether amniocentesis, transabdominal CVS, or transcervical CVS is ordered.
Biopsies may take longer, particularly those involving bone marrow or the colon. While the procedure may take only 10 to 30 minutes to perform, preparation and recovery time may add another hour if an intravenous (IV) sedative is used.
Location
Genetic samples can be obtained in a healthcare provider’s office, clinic, hospital, or an independent lab. Prenatal screening is performed as an in-office procedure. Some biopsies, such as fine needle aspiration, can be done in a practitioner’s office; others are performed on an outpatient basis at a hospital or clinic.
The actual testing of samples is conducted in a lab certified under the Clinical Laboratory Improvement Amendments (CLIA) of 1988. Today, there are more than 500 CLIA-certified genetics labs in the United States.
What to Wear
If a blood draw is required, be sure to wear short sleeves or a top with sleeves that can be easily rolled up. For prenatal screening or a biopsy, you may be asked to partially or fully undress. If so, leave any valuables at home. A hospital gown will be provided if needed.
Food and Drink
Generally speaking, there are no food or drink restrictions for a genetic test. Eating, drinking, or taking medications will not affect the outcome of the test.
While there are no food restrictions for prenatal DNA screening, fluids should be avoided prior to amniocentesis so that the bladder is empty and less likely to be perforated. By contrast, you may need a full bladder for a CVS and will be asked to drink extra fluids.
Food and drink restrictions may also apply to certain biopsy procedures, particularly those that involve the gastrointestinal tract or require sedation. Speak with your healthcare provider to ensure you adhere to the appropriate dietary guidelines.
You will also need to advise your healthcare provider if you are taking anticoagulants (blood thinners) or aspirin prior to a biopsy, as this can promote bleeding. As a rule, it is important to advise your practitioner about any medications you may be taking, prescribed or non-prescribed, prior to any medical test or investigation.
What to Bring
Be sure to bring your ID and health insurance card to your appointment. If the procedure involves sedation of any sort, either organize for a car service or bring a friend along to drive you home after the appointment.
Cost and Health Insurance
The cost of a genetic test can vary enormously, ranging from under $100 to well over $2,000, depending on the aim and complexity of the test. This does not include the extra cost of obtaining a fluid or tissue sample when prenatal screening or a tissue biopsy is indicated.
Most genetic tests require insurance pre-authorization. Some, like newborn screening and the BRCA tests used to screen for breast cancer, are classified as essential health benefits (EHB) under the Affordable Care Act, meaning that your insurer is required to cover the cost of the test and genetic counseling free of charge.
By and large, genetic tests are approved if the test helps prevent disease progression or improve treatment outcomes. With that being said, copay and coinsurance costs can often be prohibitive. If a genetic test is approved by your insurer, be sure to speak to them about any out-of-pocket expenses you are likely to incur.
If you are uninsured or underinsured, ask if the lab offers a monthly payment option or a patient assistance program with a tiered price structure for low-income families.
Direct-to-consumer ancestry tests are priced between $50 and $200, and they are not covered by insurance. Elective tests, such as paternity tests, are generally never covered by health insurance, even if mandated by a court.
Other Considerations
Some people will prefer to pay out of pocket if they fear a positive test result may impact their ability to get insurance. While health insurance is generally not an issue, call your state’s attorney general’s office to understand the health privacy laws in your state, as well as those of the federal Health Insurance Portability Accountability Act (HIPAA) of 1996.
This includes the use of home genetic kits in which manufacturers will sometime sell your data (typically aggregated without your name) to biomedical and pharmaceutical firms.
If you medical confidentiality is breached for whatever reason, you can submit a HIPAA privacy complaint to the Office of Civil Rights at the U.S. Department of Health and Human Services.
During the Test
Your testing experience will depend on the type of genetic testing you are having done, but there are some aspects that apply across the board.
Pre-Test
After signing with your ID and health insurance card, you will undergo some form of pre-test counseling. The counseling can vary based on the aims of the procedure.
For diagnostic purposes—such as confirming a long-standing illness (like Crohn’s disease) or extending the investigation of a known illness (like cancer)—pre-counseling may be constrained to understanding the goals and limitations of the test.
For screening or predictive purposes—such as identifying a prenatal birth defect, evaluating your predisposition for cancer, or estimating your chance of being a disease carrier—genetic counseling will be focused on helping you better understand the value and drawbacks of genetic testing.
Regardless, the aim of genetic counseling is to ensure you are able to provide what is called informed consent. This is defined as providing permission, without coercion or influence, based on a full understanding of the benefits and risks of a procedure.
The aim of counseling is to ensure you understand:
The purpose of the testThe type and nature of the condition being investigatedThe accuracy and limitations of the testOther testing options you can chooseThe options available to you if a disorder is identifiedDecisions you may need to make based on the resultsThe availability of counseling and support servicesYour right to refuse a testYour “right not to know” about conditions beyond the scope of the investigation
A board-certified genetic counselor will then walk you through the test and advise you as to when the results may be expected. Be sure to ask as many questions as needed, particularly if you may be faced with a difficult situation, such as the termination of pregnancy.
Throughout the Testing
Once the counseling is complete, the sample will be obtained for testing. The sample is obtained in the following ways:
A buccal smear is performed by rubbing cotton along the inside surface of the cheek. The swab is then placed in a sealed plastic tube and sent to the lab. A blood draw is performed by phlebotomist by inserting a needle into a vein and extracting 1 to 3 milliliters of blood into a test tube. A saliva sample is obtained simply by having you spit in a sterile container Newborn screening, called a Guthrie test, involves a heel prick to obtain a few drops of blood. The drops are placed on a blood spot card and sent to the lab. Amniocentesis involves the insertion of a thin, hollow needle through the abdominal wall and into your uterus to collect a small amount of amniotic fluid. CVS involves the insertion of a catheter either through the cervix or abdominal wall to obtain a tissue sample from the placenta. Fine needle aspiration (FNA) and core needle aspiration (CNA) are performed by inserting a needle through the skin into a solid tumor or bone marrow.
While surgical biopsy, using open or laparoscopic surgery, may be used to obtain hard-to-reach tissue, it would almost never be performed solely for the purpose of obtaining a genetic sample. Tissue samples may also be obtained as an adjunct to other direct diagnostic procedures, such as a colonoscopy or endoscopy.
Post-Test
In most cases, you will be able to return home once the genetic sample is obtained. If sedation was used (for a colonoscopy or bone marrow biopsy, for example), you must remain in recovery until the medical staff approves your release, usually within an hour. In that case, someone will need to drive you home.
After the Test
Any procedure involving a needle carries a risk of infection, pain, bruising, and bleeding. Call your healthcare provider if you develop a high fever or experience redness, swelling, or drainage from the biopsy site. These can be signs of an infection, requiring prompt treatment.
If sedation was used, you may experience short-term dizziness, fatigue, nausea, or vomiting once you return home. Symptoms tend to be mild and usually resolve within a day. You can reduce the risk of nausea and vomiting by drinking plenty of water. If the symptoms persist or you experience an abnormally slowed heart rate (bradycardia), call your healthcare provider immediately.
At the Lab
Depending on the aims of the test, the sample may undergo one of several processes to isolate the gene under investigation. One such process, polymerase chain reaction (PCR), is used to “amplify” the number of DNA strands in a blood sample from a few thousand to many millions.
The sample then undergoes a process called DNA sequencing to identify the exact ATCG coding in the DNA. The result is run through a computer to compare the sequence to that of the human genome reference.
A report is then generated listing all of the variants, both normal and abnormal, the information of which may require interpretation by an expert known as a geneticist.
Interpreting the Results
Depending on the test and testing facility used, it can take anywhere from one to four weeks to get your test results. Commercial labs tend to be faster than institutional or research labs.
If the test was performed for diagnostic purposes, the results will generally be reviewed with you by the healthcare provider who ordered the test. One such example is an HIV specialist who orders genotyping to determine which drugs will be most effective based on the genotype of your virus.
If the test is used for predictive or screening purposes, a genetic counselor may be on hand to explain what the results mean and do not mean.
For the most part, single-gene tests will deliver a positive, negative, or ambiguous result. By definition:
A positive result indicates that a “deleterious mutation” (also known as a “pathogenic mutation”) was found. A deleterious mutation is one in which your risk of a disease is increased, but not necessarily certain. A negative result means that no gene mutation was found. An ambiguous result, often described as a “variation of uncertain significant” (VUS), describes a mutation with unknown impact. While many such mutations are harmless, some may actually be beneficial.
Follow-Up
Genetic test results can either serve as an endpoint, enabling a definitive diagnosis and treatment plan, or a starting point, requiring further investigation or the monitoring of your health.
Among some of the scenarios you may be faced with:
Any abnormalities found during newborn screening require additional testing and/or the ongoing monitoring of the child’s health to proactively identify symptoms. Abnormalities found during prenatal screening may require preemptive therapies to minimize the impact of the disease and/or input from medical experts to help you decide whether to continue the pregnancy or not. Any abnormalities found in carrier screening tests may require input from both a geneticist (to determine the odds your baby will have a birth defect) and a fertility specialist (to explore alternative means of conception). Any abnormalities found in a predictive test require input from the appropriate specialist to explore further testing or treatment options. This may include preventive procedures, such as prophylactic mastectomy, to avoid a disease if your genetics and other risk factors place you at exceptionally high risk.
A Word From Verywell
While genetic testing can benefit the health and wellbeing of many individuals, it can complicate the lives of others. When used for elective, screening, or predictive purposes, it should only be embarked upon when you fully understand the pros and cons of testing.
Upon receiving a positive result, some people may require support from psychologists and others to help them work through complicated decisions or any uncertainties they may be faced with. To this end, most genetics specialists will work with mental health professionals skilled in helping people cope in such situations.
