Genetic Testing

Illustration of the human genome, from the genome to a chromosome, and from a chromosome to genes. Source: Wikimedia Commons.

Genetic testing identifies changes in chromosomes, genes, or proteins. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed.

Why Genetic Testing Is Done

Genetic testing is required for the diagnosis of many genetic diseases. It is also used to identify carriers. Carriers are people who carry one copy of the gene mutation, but do not have the disease: if they have children with another carrier there is a significant risk the child may have the disease. Genetic testing can be done for clinical or research purposes.

The main differences between clinical genetic testing and research testing are the purpose of the test and who receives the results. The goals of research testing include finding unknown genes, learning how genes work, and advancing our understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers. Clinical testing, on the other hand, is done to find out about an inherited disorder in an individual patient or family. People receive the results of a clinical test and can use them to help them make decisions about medical care or reproductive issues.

It is important for people considering genetic testing to know whether the test is available on a clinical or research basis. Clinical and research testing both involve a process of informed consent in which patients learn about the testing procedure, the risks and benefits of the test, and the potential consequences of testing.

Types

Genetic testing can provide information about a person’s genes and chromosomes. Available types of testing include:

Newborn screening

Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders.

Diagnostic testing

Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a person’s life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person’s choices about health care and the management of the disorder.

Carrier testing

Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple’s risk of having a child with a genetic condition.

Prenatal testing

Prenatal testing is used to detect changes in a fetus’s genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple’s uncertainty or help them make decisions about a pregnancy. It cannot identify all possible inherited disorders and birth defects, however.

Preimplantation testing

Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. In-vitro fertilization involves removing egg cells from a woman’s ovaries and fertilizing them with sperm cells outside the body. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes. Only embryos without these changes are implanted in the uterus to initiate a pregnancy.

Predictive and pre-symptomatic testing

Predictive and pre-symptomatic testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer. Pre-symptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and pre-symptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.

Genetic testing of tumours -- Molecular Pathology

Molecular Pathology is a branch of Anatomic Pathology. A molecular pathologist identifies specific mutations associated with specific tumours. Identification of these mutations may be useful for confirming the diagnosis or for predicting the behaviour of the tumor (prognosis).

Genetic testing is done on surgical or biopsy tumor specimens. The tissue may be fresh-frozen or extracted from paraffin-embedded histology blocks. Translocations are detected by PCR or FISH. Point mutations are detected by PCR. The phenotypic change in protein expression resulting from the mutation can be detected by immunohistochemistry on histological sections.

Forensic genetic testing

Forensic testing uses DNA sequences to identify an individual for legal purposes. The DNA regions tested are very polymorphic and are therefore very unlikely to be identical between unrelated individuals. These DNA sequences are as unique as fingerprints, hence the term "DNA fingerprinting". They are inherited from the biological parents. The DNA regions of interest are amplified by PCR, allowing testing on a very small quantity of tissue.

Forensic genetic testing can be ordered by a coroner or a judge for different purposes :

• Identification of an unknown cadaver or body part. Known samples of the deceased -- hair from a hairbrush, previous medical samples -- or samples from surviving blood relatives are used as reference.
• Indentification of biological traces -- blood, semen, hair, saliva, urine, sweat, skin surface cells -- to incriminate or exclude a suspect. A sample from the suspect is used as reference.
• Establish biological relationship -- paternity or maternity testing. The DNA profile of the child is compared with the putative parents.

Criminal identification usually requires a suspect. Alternatively, a large number of individuals may be screened to identify the suspect. Some inbred populations may not yield a sufficient degree of certainty. Identical twins cannot be separated by genetic testing. Genetic identification has also been used to identify animal hair or stools.

How Genetic Testing Is Done

Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or nurse practitioner can order the test. Genetic testing is often done as part of a genetic consultation.

Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person’s doctor or genetic counselor.

Newborn screening tests are done on a small blood sample, which is taken by pricking the baby’s heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder.

Before a person has a genetic test, it is important that he or she understands the testing procedure, the benefits and limitations of the test, and the possible consequences of the test results. The process of educating a person about the test and obtaining permission is called informed consent.

Benefits

Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests in some cases. A positive result can direct a person toward available prevention, monitoring, and treatment options. Some test results can also help people make decisions about having children. Newborn screening can identify genetic disorders early in life so treatment can be started as early as possible.

Risks

The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but real risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus.

Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about their results. In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern.

Genetic testing can provide only limited information about an inherited condition. The test often can’t determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed.

A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision.

Expected Outcomes

A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future, or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or pre-symptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition.

A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result.

In some cases, a negative result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result.

The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, health care professionals consider a person’s medical history, family history, and the type of genetic test that was performed.

Statistics

The cost of genetic testing can range from under $100 to more than $2,000, depending on the nature and complexity of the test. The cost increases if more than one test is necessary or if multiple family members must be tested to obtain a meaningful result. For newborn screening, costs vary by state. Some states cover part of the total cost, but most charge a fee of $15 to $60 per infant.

From the date that a sample is taken, it may take a few weeks to several months to receive the test results. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. The doctor or genetic counselor who orders a particular test can provide specific information about the cost and time frame associated with that test.

Experts on Genetic Testing

Cedars-Sinai Medical Genetics Institute

The American College of Medical Genetics

American Board of Medical Genetics

National Society of Genetic Counselors

Controversy

Direct-to-consumer genetic testing

Traditionally, genetic tests have been available only through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers order the appropriate test from a laboratory, collect and send the samples, and interpret the test results. Direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisements, or the Internet. This form of testing, which is also known as at-home genetic testing, provides access to a person’s genetic information without necessarily involving a doctor or insurance company in the process.

If a consumer chooses to purchase a genetic test directly, the test kit is mailed to the consumer instead of being ordered through a doctor’s office. The test typically involves collecting a DNA sample at home, often by swabbing the inside of the cheek, and mailing the sample back to the laboratory. In some cases, the person must visit a health clinic to have blood drawn. Consumers are notified of their results by mail or over the telephone, or the results are posted online. In some cases, a genetic counselor or other healthcare provider is available to explain the results and answer questions. The price for this type of at-home genetic testing ranges from several hundred dollars to more than a thousand dollars.

The growing market for direct-to-consumer genetic testing may promote awareness of genetic diseases, allow consumers to take a more proactive role in their health care, and offer a means for people to learn about their ancestral origins. At-home genetic tests, however, have significant risks and limitations. Consumers are vulnerable to being misled by the results of unproven or invalid tests. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. Consumers may also experience an invasion of genetic privacy if testing companies use their genetic information in an unauthorized way.

Genetic testing provides only one piece of information about a person’s health—other genetic and environmental factors, lifestyle choices, and family medical history also affect a person’s risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by at-home genetic tests. More research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing.

Information about direct-to-consumer tests is available from the Federal Trade Commission ^[1]

Genetic discrimination

Genetic discrimination occurs when people are treated differently by their employer or insurance company because they have a gene mutation that causes or increases the risk of an inherited disorder. People who undergo genetic testing may be at risk for genetic discrimination.

The results of a genetic test are normally included in a person’s medical records. When a person applies for life, disability, or health insurance, the insurance company may ask to look at these records before making a decision about coverage. An employer may also have the right to look at an employee’s medical records. As a result, genetic test results could affect a person’s insurance coverage or employment. People making decisions about genetic testing should be aware that when test results are placed in their medical records, the results might not be kept private.

Fear of discrimination is a common concern among people considering genetic testing. Several laws at the federal and state levels help protect people against genetic discrimination; however, genetic testing is a fast-growing field and these laws don’t cover every situation.

Information about genetic discrimination is available from The National Human Genome Research Institute ^[2], The Genetic Alliance ^[3], and The Australian Research Council ^[4].

Research

Recent news

• The completion of the Human Genome Project is greatly expanding the diseases and conditions amenable to genetic testing. It has also allowed the use of genetic testing to help create individualized treatment plans and to assess risks for various conditions, that in the past have not been thought of as genetic diseases.
• Research has recently been done on and is ongoing regarding the genetic susceptibility to various infectious diseases in Africa. Because there is a great deal of genetic variation among the people of Africa and because there are several infectious diseases (malaria, tuberculosis, schistosomiasis and HIV/AIDS that are problematic in the continent, genetic studies may be helpful in prevention and finding cures for these diseases. ^[5]
• A 2006 study from Thailand reviews the impact of genetic diversity on the transmission of diseases (specifically several parasitic diseases). ^[6]
• The genetics of sarcoidosis and other granulomatous diseases has also recently been studied. ^[7]

Clinical Trials

There are literally hundreds of clinical trials relating to genetic testing available at ClinicalTrials.gov: genetic testing trials. To narrow the list, genetic testing and the name of the disease can be entered in the search field.

References

1. ↑ Federal Trade Commission. FTC Facts for Consumers. At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription.
2. ↑ National Human Genome Research Institute web site. Overview of Genetic Discrimination.
3. ↑ The Genetic Alliance web site. Genetic Discrimination
4. ↑ The Australian Research Council web site. Genetic Discrimination Project
5. ↑ Sirugo G, Hennig BJ, Adeyemo AA, et al. Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics. Hum Genet. 2008 Jul;123(6):557-98. Epub 2008 May 30. Abstract
6. ↑ Tibayrenc M. Human genetic diversity and the epidemiology of parasitic and other transmissible diseases. Adv Parasitol. 2007;64:377-422. Abstract
7. ↑ Smith G, Brownell I, Sanchez M, Prystowsky S. Advances in the genetics of sarcoidosis. Clin Genet. 2008 May;73(5):401-12. Epub 2008 Feb 26. Abstract

External Links

AccessDNA.com:

• Genetic Testing

• Medical (Clinical) Genetic Testing

• Genetic Testing Methods

• Genetic Discrimination

• Direct-to-Consumer Genetic Testing

• Psychological Impact

University of Washington: GeneTests.Org.

National Human Genome Research Institute: Genome.Gov.

The Centre for Genetics Education (Australia): Genetics.com

National Newborn Screening and Genetics Resource Center.