Additional information about the oversight of genetic testing in the United States is
available from a Report of the Secretary’s Advisory Committee on Genetics, Health,
and Society (SACGHS) (http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_
oversight_report.pdf).
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Genetic Testing
What do the results of genetic tests mean?
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, healthcare
professionals consider a person’s medical history, family history, and the type of
genetic test that was done.
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 presymptomatic 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.
For more information about interpreting genetic test results:
The National Cancer Institute fact sheet Genetic Testing for Hereditary Cancer
Syndromes (http://www.cancer.gov/cancertopics/factsheet/Risk/genetic-testing) page 128
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Handbook
Genetic Testing
provides an explanation of positive and negative genetic test results. (Scroll down
to question 6, “What do the results of genetic testing mean?”)
The National Women’s Health Resource Center offers a list of questions about
genetic testing (http://www.healthywomen.org/condition/genetic-testing#hc-tab-1), including the meaning of test results, that patients and families can ask their
healthcare professional.
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Genetic Testing
What is the cost of genetic testing, and how long does it
take to get the results?
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.
For more information about the logistics of genetic testing:
EuroGentest offers a fact sheet about genetic testing laboratories
(http://www.eurogentest.org/index.php?id=621), including the reasons why some
genetic test results take longer than others.
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Genetic Testing
Will health insurance cover the costs of genetic testing?
In many cases, health insurance plans will cover the costs of genetic testing when
it is recommended by a person’s doctor. Health insurance providers have different
policies about which tests are covered, however. A person interested in submitting
the costs of testing may wish to contact his or her insurance company beforehand
to ask about coverage.
Some people may choose not to use their insurance to pay for testing because the
results of a genetic test can affect a person’s health insurance coverage. Instead,
they may opt to pay out-of-pocket for the test. People considering genetic testing
may want to find out more about their state’s privacy protection laws before they
ask their insurance company to cover the costs. (Refer to What is genetic
discrimination? (http://ghr.nlm.nih.gov/handbook/testing/discrimination) for more information.)
For more information about insurance coverage of genetic testing:
The National Human Genome Research Institute provides information about
Coverage and Reimbursement of Genetic Tests (http://www.genome.gov/19016729).
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Genetic Testing
What are the benefits of genetic testing?
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.
For more information about the benefits of genetic testing:
The National Cancer Institute provides a brief discussion of the benefits of genetic
testing (http://www.cancer.gov/cancertopics/understandingcancer/genetesting/
page29).
EuroGentest offers a fact sheet about genetic testing (http://www.eurogentest.org/
index.php?id=622), including a section on its benefits.
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Genetic Testing
What are the risks and limitations of genetic testing?
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. (Refer to What is
genetic discrimination? (http://ghr.nlm.nih.gov/handbook/testing/discrimination) for
additional information.)
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.
For more information about the risks and limitations of genetic testing:
The National Cancer Institute provides a brief discussion of the limitations of genetic
testing:
•
Limitations of Gene Testing (http://www.cancer.gov/cancertopics/
understandingcancer/genetesting/page30)
•
Major Limitations of Gene Testing (http://www.cancer.gov/cancertopics/
understandingcancer/genetesting/page31)
The American College of Medical Genetics and Genomics (ACMG) published a
policy statement about the risks associated with incorrect genetic test results or
interpretation (http://www.acmg.net/docs/LDT_Release.pdf).
EuroGentest offers a fact sheet about genetic testing (http://www.eurogentest.org/
index.php?id=622), including a section on its possible risks and limitations.
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Genetic Testing
What is 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. 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. In particular, a federal law called the Genetic Information
Nondiscrimination Act (GINA) is designed to protect people from this form of
discrimination.
GINA has two parts: Title I, which prohibits genetic discrimination in health insurance,
and Title II, which prohibits genetic discrimination in employment. Title I makes it
illegal for health insurance providers to use or require genetic information to make
decisions about a person’s insurance eligibility or coverage. This part of the law
went into effect on May 21, 2009. Title II makes it illegal for employers to use a
person’s genetic information when making decisions about hiring, promotion, and
several other terms of employment. This part of the law went into effect on November
21, 2009.
GINA and other laws do not protect people from genetic discrimination in every
circumstance. For example, GINA does not apply when an employer has fewer
than 15 employees. It does not cover people in the U.S. military or those receiving
health benefits through the Veterans Health Administration or Indian Health Service.
GINA also does not protect against genetic discrimination in forms of insurance
other than health insurance, such as life, disability, or long-term care insurance.
For more information about genetic discrimination and GINA:
The National Human Genome Research Institute provides a detailed discussion of
genetic discrimination and current laws that address this issue:
•
Genetic Discrimination (http://www.genome.gov/10002077)
•
NHGRI Genome Statute and Legislation Database
(http://www.genome.gov/PolicyEthics/LegDatabase/pubsearch.cfm)
•
Genetic Information Nondiscrimination Act (GINA) of 2008
(http://www.genome.gov/24519851)
The Genetic Alliance offers links to resources and policy statements on genetic
discrimination (http://www.geneticalliance.org/issues.discrimination).
More detailed information about GINA is available from these resources:
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Genetic Testing
•
Genetics & Public Policy Center (http://www.dnapolicy.org/resources/
WhatGINAdoesanddoesnotdochart.pdf)
•
Coalition for Genetic Fairness (http://www.geneticfairness.org/
ginaresource.html)
•
GINAHelp.org (http://www.ginahelp.org/)
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Genetic Testing
How does genetic testing in a research setting differ from
clinical genetic testing?
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, developing tests for
future clinical use, 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 (http://ghr.nlm.nih.gov/handbook/testing/
informedconsent) in which patients learn about the testing procedure, the risks and
benefits of the test, and the potential consequences of testing.
For more information about the differences between clinical and research
testing:
The Ohio State University’s Wexner Medical Center describes the difference between
clinical and research genetic testing (http://internalmedicine.osu.edu/genetics/
patient-care/clinical-cancer-genetics/genetic-testing-facts/).
The Sudden Arrhythmia Death Syndromes (SADS) Foundation also outlines the
major differences between clinical tests and research tests (http://www.sads.org/
Living-with-SADS/Genetic-Testing/Genetic-Testing---Clinical-vs--Research).
Additional information about clinical and research tests (http://www.ncbi.nlm.nih.gov/
gtr/docs/about/#tests) is available from the Genetic Testing Registry.
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Genetic Testing
What is genetic ancestry testing?
Genetic ancestry testing, or genetic genealogy, is a way for people interested in
family history (genealogy) to go beyond what they can learn from relatives or from
historical documentation. Examination of DNA variations can provide clues about
where a person’s ancestors might have come from and about relationships between
families. Certain patterns of genetic variation are often shared among people of
particular backgrounds. The more closely related two individuals, families, or
populations are, the more patterns of variation they typically share.
Three types of genetic ancestry testing are commonly used for genealogy:
•
Y chromosome testing: Variations in the Y chromosome, passed
exclusively from father to son, can be used to explore ancestry in the
direct male line. Y chromosome testing can only be done on males,
because females do not have a Y chromosome. However, women
interested in this type of genetic testing sometimes recruit a male relative
to have the test done. Because the Y chromosome is passed on in the
same pattern as are family names in many cultures, Y chromosome
testing is often used to investigate questions such as whether two families
with the same surname are related.
•
Mitochondrial DNA testing: This type of testing identifies genetic variations
in mitochondrial DNA. Although most DNA is packaged in chromosomes
within the cell nucleus, cell structures called mitochondria also have a
small amount of their own DNA (known as mitochondrial DNA). Both
males and females have mitochondrial DNA, which is passed on from
their mothers, so this type of testing can be used by either sex. It provides
information about the direct female ancestral line. Mitochondrial DNA
testing can be useful for genealogy because it preserves information
about female ancestors that may be lost from the historical record because
of the way surnames are often passed down.
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Genetic Testing
•
Single nucleotide polymorphism (http://ghr.nlm.nih.gov/handbook/
genomicresearch/snp) testing: These tests evaluate large numbers of
variations (single nucleotide polymorphisms or SNPs) across a person’s
entire genome. The results are compared with those of others who have
taken the tests to provide an estimate of a person’s ethnic background.
For example, the pattern of SNPs might indicate that a person’s ancestry
is approximately 50 percent African, 25 percent European, 20 percent
Asian, and 5 percent unknown. Genealogists use this type of test because
Y chromosome and mitochondrial DNA test results, which represent only
single ancestral lines, do not capture the overall ethnic background of an
individual.
Genetic ancestry testing has a number of limitations. Test providers compare
individuals’ test results to different databases of previous tests, so ethnicity estimates
may not be consistent from one provider to another. Also, because most human
populations have migrated many times throughout their history and mixed with
nearby groups, ethnicity estimates based on genetic testing may differ from an
individual’s expectations. In ethnic groups with a smaller range of genetic variation
due to the group’s size and history, most members share many SNPs, and it may
be difficult to distinguish people who have a relatively recent common ancestor,
such as fourth cousins, from the group as a whole.
Genetic ancestry testing is offered by several companies and organizations. Most
companies provide online forums and other services to allow people who have
been tested to share and discuss their results with others, which may allow them
to discover previously unknown relationships. On a larger scale, combined genetic
ancestry test results from many people can be used by scientists to explore the
history of populations as they arose, migrated, and mixed with other groups.
For more information about genetic ancestry testing:
The British Broadcasting Company offers an introductory article on genetic
genealogy (http://www.bbc.co.uk/history/familyhistory/next_steps/genetic_
genealogy_01.shtml).
The University of Utah provides video tutorials (http://learn.genetics.utah.edu/content/
extras/molgen/) on molecular genealogy.
The International Society of Genetic Genealogy (http://www.isogg.org/) promotes the use of DNA testing in genealogy.
The American Society of Human Genetics (ASHG) developed a position paper on
ancestry testing (http://www.ashg.org/pdf/ASHGAncestryTestingStatement_
FINAL.pdf).
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Handbook
Gene Therapy
Chapter 7
Gene Therapy
Table of Contents
What is gene therapy?
How does gene therapy work?
Is gene therapy safe?
What are the ethical issues surrounding gene therapy?
Is gene therapy available to treat my disorder?
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Gene Therapy
What is gene therapy?
Gene therapy is an experimental technique that uses genes to treat or prevent
disease. In the future, this technique may allow doctors to treat a disorder by
inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers
are testing several approaches to gene therapy, including:
•
Replacing a mutated gene that causes disease with a healthy copy of
the gene.
•
Inactivating, or “knocking out,” a mutated gene that is functioning
improperly.
•
Introducing a new gene into the body to help fight a disease.
Although gene therapy is a promising treatment option for a number of diseases
(including inherited disorders, some types of cancer, and certain viral infections),
the technique remains risky and is still under study to make sure that it will be safe
and effective. Gene therapy is currently only being tested for the treatment of
diseases that have no other cures.
For general information about gene therapy:
MedlinePlus from the National Library of Medicine offers a list of links to information