Genetic Testing; Key Q&A.* What is genetic testing?
A genetic test looks at a particular aspect of your genetic makeup, either directly through gene sequencing or indirectly through measure of marker chemicals. Testing may be done for a variety of purposes:
* Diagnosis, to determine if a person has genetic disorder (often performed in conjunction with analysis of symptoms)
* Risk screening, to determine if a person is at increased risk of having a genetic disorder (with follow-up diagnostics usually called for if a test is positive)
* Predisposition testing, to determine if a person is at higher risk of developing a particular disease later in life
* Carrier testing, to determine if a person is a carrier of a disease-causing mutation and may be at risk of having a child with the disease
* What does it mean if I'm a carrier for a disease?
Genes come in pairs, and a carrier of a recessive recessive /re·ces·sive/ (re-ses´iv)
1. tending to recede; in genetics, incapable of expression unless the responsible allele is carried by both members of a pair of homologous chromosomes.
2. disease has one mutated, disease-causing gene and a corresponding normal gene. The normal gene overrides the mutated one and the person never develops the disease. If two carriers of the same disease-causing gene have a child, however, that child has a 25 percent chance of having the disease (because of a 25 percent chance of inheriting two mutated copies of the gene), a 50 percent chance of being a carrier and a 25 percent chance of not inheriting the mutation at all.
* If my partner and I have carrier testing, will the results tell us whether or not our children will be affected?
In most cases, the test will provide only guidance as to your child's risk for being born with a particular disorder or being a carrier of the disease. Because you contribute only one of the two copies you have of each gene, each child has a 50 percent chance of inheriting any particular mutation from you. Each child likewise has a 50 percent chance of inheriting any particular mutation your partner has. Thus, if you are both carriers of the same autosomal recessive disorder, each child has a 25 percent risk of being born with the disease, a 50 percent risk of being a carrier, and a 25 percent chance of not inheriting a mutation at all. A genetic counselor can help you sort through the possible combinations in your situation and describe options for pregnancy planning and prenatal testing.
* Why do I need a genetic counselor in addition to my doctor?
Most doctors have not been as thoroughly trained in genetics and genetic testing as a genetic counselor, plus most do not have time to spend an hour or more providing the background information necessary for you to make an informed decision. Hence, even physicians agree that genetic counseling is essential and many make referrals when the issue arises. Genetic counselors usually work with geneticists (M.D. or Ph.D.s), particularly for more complex cases.
* If I have a test, will I face job or insurance discrimination if the result is positive?
So far, there is little evidence that insurers and employers are discriminating on the basis of genetic test results. However, the field is still young and as testing becomes more widespread, it's possible that discrimination will become a bigger problem. Federal law prohibits insurers from genetic discrimination in offering coverage under group plans, and many states have enacted privacy and discrimination laws of varying degrees of potency. If you are concerned about protecting your privacy, you may want to consider paying for a test out of pocket even if your insurer provides coverage. Also, be sure to ask about the privacy protections in place at the center where you have a test performed. Some centers maintain separate records for genetic information that may be released only with your permission.
* Why are some genetic tests so much more expensive than others?
Some tests look for mutations by actually sequencing the gene; these tests, which may cost upwards of $2,000, look for mutations by determining the exact order of the chemicals that comprise the gene and compare the order to that of a normal gene. Other, less expensive tests look for the most common known disease-causing mutations. It's like the difference between looking at a few frames of a film for a problem and scrutinizing every frame in the reel.
* A relative has cancer-am I at risk, too?
Your family history provides the best clues. Two or more relatives with early onset (before age 50) of related cancers, or diagnosis of two or more related cancers in the same person suggest the possibility of a genetic link that could put you at risk. Related cancers are not always as obvious as you might think. For example, colon cancer and endometrial cancer can be caused by the same genetic mutation. Talk to a genetic counselor to get a better idea of your risk and find out whether predisposition testing is available.
* Isn't my health my own business? Why should my extended family be involved?
By their very nature, genetic diseases are a family affair, with mutations passed on to multiple generations. When a disease is clearly hereditary, testing positive for a disease-causing mutation or being diagnosed with the disease provides knowledge that other family members may be at risk. A genetic counselor can help you identify who may be at risk and should be notified, and can help you handle the situation if there is estrangement between relatives.
* What's the difference between amniocentesis amniocentesis (ăm'nēō'sĕntē`sĭs), diagnostic procedure in which a sample of the amniotic fluid surrounding a fetus is removed from the uterus by means of a fine needle inserted through the abdomen of the pregnant woman (see and chorionic villus sampling chorionic villus sampling (CVS) or chorionic villus biopsy (CVB) (kōr'ē-ŏn`ĭk, kôr'–), diagnostic procedure in which a sample of chorionic villi from the developing placenta is removed from the ? How do I decide which is right for me?
Both procedures provide for diagnosis of specific chromosomal and genetic disorders in the fetus. Amniocentesis is more likely to be offered as a follow-up to an abnormal maternal serum screening test because results of the screen are obtained too late in pregnancy for CVS (1) (Concurrent Versions System) A version control system for Unix that was initially developed as a series of shell scripts in the mid-1980s. CVS maintains the changes between one source code version and another and stores all the changes in one file. . However, CVS, which is done at 10 to 12 weeks gestation, or amniocentesis, are offered in the following situations:
* You will be 35 or older at delivery
* A genetic disorder has surfaced on either side of the family
* You or your partner has had a previous child with a birth defect
* You and your partner are carriers of the same recessive disorder
Both chorionic villus sampling (CVS) and amniocentesis can cause cramping, and a small number of women have miscarriages following the procedures (the risk is higher with CVS, but still only about one percent). It takes one to two weeks to get results from either test.
Amniocentesis is performed more frequently and should be the choice if you're at risk having a child with neural tube defects. The procedure is performed at 15 to 18 weeks of pregnancy.
CVS can be performed earlier, at 10 to 12 weeks, and is popular with parents who would like to know results before the pregnancy starts to show. The procedure is not available everywhere, however.
* If I get a negative result from a cancer predisposition test, can I still develop that particular kind cancer?
Yes. To take a familiar example, your lifetime risk for breast cancer, even in the absence of a gene mutation, is about 12.5 percent. At least 90 percent of breast cancer is "sporadic," without a hereditary component. A negative BRCA BRCA
One of two genes (designated BRCA1 and BRCA2) that help repair damage to DNA, but when inherited in a defective state increase the risk of breast and ovarian cancer. test or clean family history does not give you a free pass on breast cancer. It simply means you don't face a higher-than-average risk for the disease.
FDA Approves Lower Dose of Prempro, A Combination Estrogen and Progestin Drug for Postmenopausal Women. Press Release, March 13, 2003. http://www.fda.gov
"FDA Approves New Labels for Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women Following Review of Women's Health Initiative Women's Health Initiative A 15-yr, $628 million project involving 1. An observational study of the health habits and medical Hx of ±100,000 ♀ 2. Data." FDA News/Press Release. January 8, 2003. http://www.fda.gov. Accessed Dec. 2003.
Lacey, James V., et al. "Menopausal Hormone Replacement Therapy Hormone Replacement Therapy Definition
Hormone replacement therapy (HRT) is the use of synthetic or natural female hormones to make up for the decline or lack of natural hormones produced in a woman's body. and Risk of Ovarian Cancer." JAMA 2002. Vol. 288:334-341.368-369.
Grady D, Herrington D, Bittner V, et al, for the HERS Research Group. Heart and estrogen/progestin replacement study follow-up (HERS II): Part 1. Cardiovascular outcomes during 6.8 years of hormone therapy. JAMA 2002;288:49-57.
Hulley S, Furberg C, Barrett-Connor E, et al, for the HERS Research Group. Heart and estrogen/progestin replacement study follow-up (HERS II): Part 2. Non-cardiovascular outcomes during 6.8 years of hormone therapy. JAMA 2002;288:58-66.
Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial A randomized controlled trial (RCT) is a scientific procedure most commonly used in testing medicines or medical procedures. RCTs are considered the most reliable form of scientific evidence because it eliminates all forms of spurious causality. . JAMA 2002; 288:321-333.
"Women's Health Initiative," National Heart, Lung and Blood Institute. http://www.nhlbi.nih.gov. Updated Oct. 2003; accessed Dec. 2003.
The Menopause Guidebook: Helping Women Make Informed Healthcare Decisions through Perimenopause perimenopause /peri·meno·pause/ (-men´o-pawz) the time just before and after menopause.perimenopau´sal
n. and Beyond. North American Menopause Society: May 2003; http://www.menopause.org. Accessed Dec. 2003.
About genetics services (overview material). GeneTests (Collaborative effort of the NIH, HHS HHS Department of Health and Human Services. , University of Washington and Children's Hospital and Regional Medical Center of Seattle). Revised 2000. http://www.genetests.org. Accessed Jan. 2002.
Genzyme Genetics patient information: Conditions and Tests. http://www.genzymegenetics.com. Accessed Dec. 2003.
Ashkenazi Jewish Genetic Diseases. Albert Einstein Health Care Network. Updated Sept. 2001. http://www.einstein.edu. Accessed Dec. 2003.
Burke, Wylie, E Thomas, et al. Hereditary hemochromatosis Hemochromatosis Definition
Hemochromatosis is an inherited blood disorder that causes the body to retain excessive amounts of iron. This iron overload can lead to serious health consequences, most notably cirrhosis of the liver. : gene discovery and its implications for population-based screening. Journal of the American Medical Association JAMA: The Journal of the American Medical Association is an international peer-reviewed general medical journal, published 48 times per year by the American Medical Association. JAMA is the most widely circulated medical journal in the world. . July 8, 2000; Vol. 280, pp. 172-78.
Celiac Disease. National Institute of Diabetes and Digestive and Kidney Disease. July 2003. http://www.niddk.nih.gov. Accessed Dec. 2003.
Facts About Cystic Fibrosis. National Heart, Lung and Blood Institute. http://www.nhlbi.nih.gov. Accessed Jan. 2002.
Facts about Fragile X Syndrome Fragile X Syndrome Definition
Fragile X syndrome is the most common form of inherited mental retardation. Individuals with this condition have developmental delay, variable levels of mental retardation, and behavioral and emotional difficulties. . National Institute of Child Health and Human Development. Last modified Nov. 2002. http://www.nichd.nih.gov. Accessed Dec. 2003.
Facts About Sickle Cell Anemia sickle cell anemia
A chronic, usually fatal inherited form of anemia marked by crescent-shaped red blood cells, occurring almost exclusively in Blacks, and characterized by fever, leg ulcers, jaundice, and episodic pain in the joints. . National Heart, Lung and Blood Institute. http://www.nhlbi.nih.gov. Accessed Jan. 2002.
Multiple Endocrine Neoplasia neoplasia /neo·pla·sia/ (-pla´zhah) the formation of a neoplasm.
cervical intraepithelial neoplasia Type 1. National Institute of Diabetes and Digestive and Kidney Diseases. Last reviewed June 2002. http://www.niddk.nih.gov. Accessed Dec. 2003.
Hemochromatosis. National Institute of Diabetes and Digestive and Kidney Disease. Aug. 2002. http://digestive.niddk.nih.gov. Accessed Dec. 2003.
Huntington's Disease. National Institute of Neurological Disorders and Stroke. Last reviewed July 2001. http://www.ninds.nih.gov. Accessed Jan. 2002.
Neurofibromatosis Neurofibromatosis Definition
Neurofibromatosis (NF), or von Recklinghausen disease, is a genetic disease in which patients develop multiple soft tumors (neurofibromas). These tumors occur under the skin and throughout the nervous system. . National Institute of Neurological Disorders and Stroke. Reviewed May 2003. http://www.ninds.nih.gov. Accessed Dec. 2003.
NHGRI NHGRI National Human Genome Research Institute Glossary of Genetic Terms. National Human Genome Research Institute. http://www.genome.gov. Accessed Dec. 2003.
NINDS von Hippel Lindau Disease Information Page. National Institute of Neurological Disorders and Stroke. Reviewed May 2002. http://www.ninds.nih.gov. Accessed Dec. 2003.
Understanding Alpha-1 Antitrypsin Deficiency. National Heart, Lung and Blood Institute. http://www.nhlbi.nih.gov. Accessed Jan. 2002.
MEDLINEplus: Alpha-1 Antitrypsin Deficiency. Updated Jan. 2002. http://www.nlm.nih.gov. Accessed Jan. 2002.
Understanding Gene Testing. National Cancer Institute. http://www.accessexcellence.org. Accessed Jan. 2002.
Editorial Staff of the National Women's Health Resource Center 2002/12/20 2005/03/16 Today, there are hundreds of different genetic tests, some of them for relatively common disorders such as cystic fibrosis, and some for very rare diseases. A genetic test is fundamentally different from other kinds of diagnostic tests you might take. BRCA,Chorionic villus sampling,Chromosome,Genetic counseling,Genetic testing,Genetics,Maternal serum screening,Preimplantation genetic diagnosis preimplantation genetic diagnosis: see embryo biopsy.