Home > Encyclopedia of Nursing & Allied Health > Genetic Testing

Definition

A genetic test examines the genetic information contained inside a person's cells, called DNA, to determine if that person has or will develop a certain disease or could transmit a disease to a child. Genetic tests also determine whether or not couples are at a higher risk than the general population for having a child affected with a genetic disorder.

Purpose

Some families or ethnic groups have a higher incidence of a certain disease than do the population as a whole. For example, individuals of Eastern European, Ashkenazi Jewish descent are at higher risk for carrying genes for rare conditions such as Tay-Sachs disease (a lipid storage disease) that occur much less frequently in populations from other parts of the world. Before having a child, a couple from such a family or ethnic group may want to know if their child would be at risk of having that disease. Genetic testing for this type of purpose is called genetic screening.

During pregnancy, a baby's cells can be studied for certain genetic disorders or chromosomal problems such as Down syndrome. Chromosome testing is most commonly offered when a mother is 35 years or older at the time of delivery. When there is a family medical history of a genetic disease or there are individuals in a family affected with developmental and physical delays, genetic testing may also be offered during pregnancy. Genetic testing during pregnancy is called prenatal diagnosis.

Prior to becoming pregnant, couples who are having difficulty conceiving a child or who have had multiple miscarriages may be tested to see if a genetic cause can be identified.

A genetic disease may be diagnosed at birth by performing a physical evaluation of the baby and observing characteristics of the disorder. Genetic testing can help to confirm the diagnosis made by a physical evaluation. In addition, biochemical tests (e.g., blood phenylalanine measurement) are performed routinely on all newborns to screen for certain genetic diseases that can affect a newborn baby's health shortly after birth.

There are several genetic diseases and conditions in which the symptoms do not occur until adulthood. One such example is Huntington's disease. This is a serious disorder affecting the way in which individuals walk, talk and function on a daily basis. Genetic testing may be able to determine if someone at risk for the disease will in fact develop the disease.

Some genetic abnormalities may make a person more susceptible to certain types of cancer. Testing for these abnormalities can help predict a person's risk. Other types of genetic tests help diagnose, predict, and monitor the course of certain kinds of cancer, particularly leukemia, lymphoma, and breast cancer.

Precautions

Genetic tests are performed on cells derived from blood, bone marrow, amniotic fluid, or tissues. The health care worker collecting the specimen should observe universal precautions for the prevention of transmission of bloodborne pathogens. Because genetic testing is not always accurate and because there are many concerns surrounding insurance and employment discrimination for an individual receiving a genetic test, genetic counseling should always be performed prior to genetic testing. A genetic counselor is an individual with a master's degree in genetic counseling. A medical geneticist is a physician specializing and board certified in genetics.

A genetic counselor reviews a person's family history and medical records and the reason for the test. The counselor explains the likelihood that the test will detect all possible causes of the disease in question (known as the sensitivity of the test), and the likelihood that the disease will develop if the test is positive (known as the positive predictive value of the test).

Learning about the disease in question, the benefits and risks of both a positive and a negative result, and what treatment choices are available if the result is positive, will help prepare a person undergoing testing. During the genetic counseling session, an individual interested in genetic testing will be asked to consider how the test results may affect his or her life, family, and future decisions.

After this discussion, persons should have the opportunity to indicate, in writing, that they gave informed consent to have the test performed, verifying that the counselor provided complete and understandable information.

Description

Genes and chromosomes

Deoxyribonucleic acid (DNA) is a long molecule made up of two strands of genetic material coiled around each other in a unique double helix structure. Francis Crick and James Watson discovered this structure in 1953. Each strand of DNA consists of a backbone of deoxyribose sugars linked together by phosphate groups. Each sugar is bound (with a covalent bond) to one of four bases, adenine, guanine, thymine or cytosine. The two strands are held together by hydrogen bonds between the bases. Adenine pairs with thymine and guanine pairs with cytosine.

Most of the DNA is found in the nucleus of the cell. Each person's DNA is a unique blueprint, giving instructions for that person's physical traits, such as eye color, hair texture, height, and susceptibility to disease. DNA is organized into structures called chromosomes.

The instructions are contained as a code spelled out by the order of the four bases in each of the strands of DNA. When a base pair is out of order, or is missing, then cells may not produce an important protein or may produce an abnormal protein resulting in a genetic disorder. While genes are found in every nucleated cell of the human body, not every gene is functioning all of the time. Some genes are turned on during critical points in development and then remain silent for the rest of a cell's life. Other genes remain active throughout life so that cells can produce important proteins that help humans digest food properly or fight off the common cold.

In the human genome there are 3.1 billion bases and approximately 100,000 genes. Approximately 95% of DNA consists of non-coding regions called introns. The remaining 5% consists of coding regions called exons, which are the structural units that form genes. Within the exon, the specific order of the base pairs on a strand of DNA dictates the order of amino acids that comprise the protein made when the gene is transcribed and translated. A grouping of three sequential base pairs within the exon is called a codon. Each codon, or triplet, codes for an amino acid. These are added in tandem to form a protein. A string of many codons together can be thought of as a series of words all coming together to make a sentence. This sentence provides the instructions for cells to make a protein that is needed in order for the body to function properly.

Human DNA strands containing a hundred to several thousand genes are found on structures called chromosomes. Each cell typically has 46 chromosomes arranged into 23 pairs. Each parent contributes one chromosome to each pair. The first 22 pairs are called autosomal chromosomes, or non-sex chromosomes and are assigned a number from one to 22. The last pair are the sex chromosomes and include the X and the Y chromosomes. If a child receives an X chromosome from each parent, the child is female. If a child receives an X from the mother, and a Y from the father, the child is male.

Just as each parent contributes one chromosome to each pair, so each parent contributes one gene from each chromosome. The pair of genes produces a specific trait in the child. In autosomal dominant conditions, it takes only one copy of a gene to influence a specific trait. The stronger gene is called dominant; the weaker gene is said to be recessive. Two copies of a recessive gene are needed to express a trait while only one copy of a dominant gene is needed. Some genes, (for example, those coding for blood groups) exhibit codominant expression. In this case, both genes are active and produce traits. Human sex chromosomes, the X and the Y also contain important genes. Some genetic diseases are caused by missing or altered genes on one of the sex chromosomes. Males are most often affected by sex chromosome diseases when they inherit an X chromosome with missing or mutated genes from their mothers.

Types of genetic mutations

Genetic disease results from a change, or mutation, in a chromosome or in one of several base pairs on a gene. Some people inherit such mutations from their parents. These are called hereditary or germline mutations. Other mutations can occur spontaneously, or for the first time in an affected child. For many of the adult on-set diseases, genetic mutations can occur over the lifetime of an individual. These are called acquired or somatic mutations and occur while cells are making copies of themselves or dividing in two. Environmental effects, such as radiation or other chemicals, can also contribute to these types of mutations.

There are a variety of different types of mutations that can occur in the genetic code to cause disease. For each genetic disease, there may be more than one type of mutation to cause the disease. For some genetic diseases, the same mutation occurs in every individual affected with the disease. For example, the most common form of dwarfism, called achondroplasia, is caused by a single base pair substitution. This same mutation occurs in all individuals affected with the disease. Other genetic diseases are caused by different types of genetic mutations that may occur anywhere along the length of a gene. For example, cystic fibrosis, the most common genetic disease in the Caucasian population, is caused by any of several hundred different gene mutations. Individual families may carry the same mutation as each other, but not as the rest of the population affected with the same genetic disease.

Some genetic diseases occur as a result of a larger mutation that can occur when a chromosome itself is either rearranged or altered or when a baby is born with more than the expected number of chromosomes. There are only a few types of chromosome rearrangements that are possibly hereditary, or passed on from the mother or the father. The majority of chromosome alterations, where a baby is born with too many chromosomes or missing a chromosome, occur sporadically or for the first time with a new baby.

The type of mutation that causes a genetic disease will determine the type of genetic test to be performed. In some situations, more than one type of genetic test will be performed to arrive at a diagnosis. The cost of genetic tests vary. Chromosome studies can cost hundreds of dollars and some gene studies, thousands. Insurance coverage also varies among companies and the policies. It may take several days or several weeks to complete a test. Research testing, when the exact location of a gene has not yet been identified, can require several months to years for results.

Types of genetic testing

DIRECT DNA MUTATION ANALYSIS. Direct DNA sequencing examines the base pair sequence of a gene for specific mutations. Some genes contain more than 100,000 bases and a mutation of any one base can make the gene nonfunctional and cause disease. As the number of possible mutations increases, the less likely a test is able to detect all of them. DNA sequencing is a research tool that is used to identify the order of bases in cloned genes. Base sequencing identifies the specific mutation. Once this is known a DNA probe can be made that recognizes the mutation. DNA probes typically contain 20-60 bases to insure that they bind only to the specific mutation site. DNA testing for disease genes is usually performed on white blood cells but can also be performed on other tissues.

There are several different lab techniques used to test for a direct mutation. One early approach begins by using chemicals to separate DNA from the rest of the cell. Special enzymes (called restriction enzymes) are added to the DNA. The enzymes then function like scissors and cut the strands in specific places. Next, the DNA fragments are separated by size using a process called electrophoresis. The fragments are treated chemically to separate them into single stranded fragments and transferred to a nylon filter, a process called Southern blotting. The DNA probe is added to the fragments. The probe is designed to bind to the specific mutated portion of the gene. The probe is labeled with a radioactive isotope. When the probe hybridizes with the target sequence containing the mutation, it will render this piece of DNA on the filter radioactive. The radioactivity will expose a piece of x-ray film layered over the nylon filter, and the mutation will appear as a band in the expected location.

When only small quantities of DNA are available, as in prenatal diagnosis, the target DNA from the fetal cells must first be amplified. This is accomplished by a method known as the polymerase chain reaction. This procedure can copy a specific sequence of DNA that frames the gene to be tested. Up to one million copies can be made in as little as two hours.

INDIRECT DNA TESTING. Family linkage studies are performed to study a disease when the exact type and location of the genetic alteration is not known but the general location on the chromosome has been identified. These studies are possible when a chromosome marker has been found to be associated with a disease. Chromosomes contain certain regions that vary in appearance between individuals. These regions are called

polymorphisms and do not cause a genetic disease to occur. If a polymorphism is always present in family members with the same genetic disease, and absent in family members without the disease, it is likely that the gene responsible for the disease is near that polymorphism. The gene mutation can be indirectly detected in family members by looking for the polymorphism.

To look for the polymorphism, DNA is isolated from cells in the same way it is for direct DNA mutation analysis. A restriction enzyme known to cut the DNA at the site where the polymorphism occurs is added. If the polymorphism is present, the restriction enzyme will not recognize the site and will not cut the DNA there. This results in a larger size fragment of DNA. If sufficient DNA is present, the fragments can be separated by electrophoresis, and the DNA bands are stained with ethidium bromide to visualize the position of the bands. If the amount of DNA is small, the double stranded fragments can be separated and a DNA probe can be used to determine whether the polymorphism is present. The pattern of banding of a person being tested for the disease is compared to the pattern from a family member affected by the disease.

Linkage studies have disadvantages not found in direct DNA mutation analysis. These studies require multiple family members to participate in the testing. If key family members choose not to participate, the incomplete family history may make testing other members useless. The indirect method of detecting a mutated gene also causes more opportunity for error, and many disease genes are not associated with polymorphisms.

CHROMOSOME ANALYSIS. Various genetic syndromes are caused by structural chromosome abnormalities. To analyze a person's chromosomes, cells are allowed to grow and multiply in the laboratory until they reach a certain stage of growth. The length of growing time varies with the type of cells. Cells from blood and bone marrow take one to two days, fetal cells from amniotic fluid require seven to 10 days.

When the cells are ready, they are placed on a microscope slide using a technique to make them swell, allowing easier visualization of chromosomes. The slides are stained. The stain creates a banding pattern unique to each chromosome. Under a microscope, the chromosomes are counted, identified, and analyzed based on their size, shape, and stained appearance.

A karyotype is the final step in the chromosome analysis. After the chromosomes are counted, a photograph is taken of the chromosomes from one or more cells as seen through a microscope. Then the chromosomes are cut out and arranged side-by-side with their partner in ascending numerical order, from largest to smallest. The karyotype is done either manually or using a computer attached to the microscope. Chromosome analysis is also called cytogenetics.

Applications for genetic testing

NEWBORN SCREENING. Genetic testing is used most often for newborn screening. Every year, millions of newborn babies have their blood samples tested for potentially serious genetic diseases. Phenylketonuria is the genetic disease test most commonly performed.

CARRIER TESTING. An individual who has a gene associated with a disease but never exhibits any symptoms of the disease is called a carrier. A carrier is a person who is not affected by a possessed mutated gene, but can pass the gene to an offspring. Genetic tests have been developed that tell prospective parents whether or not they are carriers of certain diseases. If one or both parents are carriers, the risk of passing the disease to a child can be predicted.

To predict the risk, it is necessary to know if the gene in question is autosomal or sex-linked. If the gene is carried on any one of chromosomes one through 22, the resulting disease is called an autosomal disease. If the gene is carried on the X or Y chromosome, it is called a sex-linked disease.

Sex-linked diseases, such as the bleeding condition hemophilia, are usually carried on the X chromosome. A woman who carries a disease-associated mutated gene on one of her X chromosomes has a 50% chance of passing that gene to her son. A son who inherits that gene will develop the disease because he does not have another normal copy of the gene on a second X chromosome to compensate for the abnormal copy. A daughter who inherits the disease associated gene from her mother, on one of her X chromosomes will become a carrier and be at risk for having a son affected with the disease.

The risk of passing an autosomal disease to a child depends on whether the gene is dominant or recessive. A prospective parent carrying a dominant gene, has a 50% chance of passing the gene to a child. A child needs to receive only one copy of the mutated gene to be affected by the disease.

If the gene is recessive, a child needs to receive two copies of the mutated gene, one from each parent, to be affected by the disease. When both prospective parents are carriers, their child has a 25% chance of inheriting two copies of the mutated gene and being affected by the disease; a 50% chance of inheriting one copy of the mutated gene and being a carrier of the disease but not affected; and a 25% chance of inheriting two normal genes. When only one prospective parent is a carrier, a child has a 50% chance of inheriting one mutated gene and being an unaffected carrier of the disease, and a 50% chance of inheriting two normal genes.

Cystic fibrosis is a disease that affects the lungs and pancreas and is discovered in early childhood. It is the most common autosomal recessive genetic disease found in the Caucasian population: one in 25 people of Northern European ancestry are carriers of a mutated cystic fibrosis gene. The gene, located on chromosome seven, was identified in 1989.

The gene mutation for cystic fibrosis is detected by a direct DNA test. Over 600 mutations of the cystic fibrosis gene have been identified. Each of these mutations cause the same disease. Tests are available for the most common mutations. Tests that check for the 86 most common mutations in the Caucasian population will detect 90% of carriers for cystic fibrosis. The percentage of mutations detected varies according to an individual's ethnic background. When persons test negative, it is likely, but not guaranteed that they do not have the gene. Both prospective parents must be carriers of the gene to conceive a child with cystic fibrosis.

Tay-Sachs disease, also autosomal recessive, affects children primarily of Ashkenazi Jewish descent. Children with this disease die between the ages of two and five. This disease was previously detected by looking for a missing enzyme. The mutated gene has now been identified and can be detected using direct DNA mutation analysis.

PRESYMPTOMATIC TESTING. Not all genetic diseases show their effect immediately at birth or early in childhood. Although the gene mutation is present at birth, some diseases do not appear until adulthood. If a specific mutated gene responsible for a late-onset disease has been identified, a person from an affected family can be tested before symptoms appear.

Huntington's disease is one example of a late-onset autosomal dominant disease. Its symptoms of mental confusion and abnormal body movements do not appear until middle to late adulthood. The chromosome location of the gene responsible for Huntington's chorea was located in 1983 after studying the DNA from a large Venezuelan family affected by the disease. Ten years later, the gene was identified. A test is now available to detect the presence of the expanded base pair sequence responsible for causing the disease. The presence of this expanded sequence means a person will develop the disease.

Another late onset condition, Alzheimer's disease, is not as well understood as Huntington's disease. The specific genetic cause of Alzheimer's disease is not as clear. Although many cases appear to be inherited in an autosomal dominant pattern, many cases exist as single incidents in a family. Like Huntington's disease, symptoms of mental deterioration first appear in adulthood. Genetic research has found an association between this disease and genes on four different chromosomes. The validity of looking for these genes in a person without symptoms or without family history of the disease is still being studied.

CANCER SUSCEPTIBILITY TESTING. Cancer can result from an inherited (germline) mutated gene or a gene that mutated sometime during a person's lifetime (acquired mutation). Some genes, called tumor suppressor genes, produce proteins that protect the body from cancer. If one of these genes develops a mutation, it is unable to produce the protective protein. If the second copy of the gene is normal, its action may be sufficient to continue production, but if that gene later develops a mutation, the person is vulnerable to cancer. Other genes, called oncogenes, are involved in the normal growth of cells. A mutation in an oncogene can cause too much growth, the beginning of cancer.

Direct DNA tests are currently available to look for gene mutations identified and linked to several kinds of cancer. People with a family history of these cancers are those most likely to be tested. If one of these mutated genes is found, the person is more susceptible to developing the cancer. The likelihood that the person will develop the cancer, even with the mutated gene, is not always known because other genetic and environmental factors are also involved in the development of cancer.

Cancer susceptibility tests are most useful when a positive test result can be followed with clear treatment options. In families with familial polyposis of the colon, testing a child for a mutated APC gene can reveal whether or not the child needs frequent monitoring for the disease. In families with potentially fatal familial medullary thyroid cancer or multiple endocrine neoplasia type two, finding a mutated RET gene in a child provides the opportunity for that child to have preventive removal of the thyroid gland. In the same way, MSH1 and MSH2 mutations can reveal which members in an affected family are vulnerable to familiar colorectal cancer and would benefit from aggressive monitoring.

In 1994, a mutation linked to early-onset familial breast and ovarian cancer was identified. BRCA1 is located on chromosome 17. Women with a mutated form of this gene have an increased risk of developing breast and ovarian cancer. A second related gene, BRCA2, was later discovered. Located on chromosome 13, it also carries increased risk of breast and ovarian cancer. Although both genes are rare in the general population, they are slightly more common in women of Ashkenazi Jewish descent.

When a woman is found to have a mutation of one of these genes, the likelihood that she will get breast or ovarian cancer increases, but not to 100%. Other genetic and environmental factors may also influence the outcome.

Testing for these genes is most valuable in families where a mutation has already been found. BRCA1 and BRCA2 are large genes; BRCA1 includes 100,000 bases. More than 120 mutations to this gene have been discovered, but a mutation could occur in any one of the bases. Studies show tests for these genes may miss 30% of existing mutations. The rate of missed mutations, the unknown disease likelihood in spite of a positive result, and the lack of a clear preventive response to a positive result, make the value of this test for the general population uncertain.

PRENATAL AND POSTNATAL CHROMOSOME ANALYSIS. Chromosome analysis is usually performed on fetal cells when a mother will be age 35 or older at the time of delivery, has experienced multiple miscarriages, or reports a family history of a genetic abnormality. Prenatal testing is done on the fetal cells from a chorionic villus sampling (from the baby's developing placenta) at nine to 12 weeks of gestation or from the amniotic fluid (the fluid surrounding the baby) at 15-18 weeks of pregnancy. Cells from amniotic fluid usually must grow for seven to 10 days before they are ready to be analyzed. Chorionic villi cells have the potential to grow faster and can be analyzed sooner.

Chromosome analysis using blood cells is performed for a child who is born with or later develops signs of mental retardation or physical malformation. In an older child, chromosome analysis may be requested to investigate developmental delays.

Extra or missing chromosomes cause mental and physical abnormalities. A child born with an extra chromosome 21 (trisomy 21) has Down syndrome. An extra chromosome 13 or 18 also produces well known syndromes. A missing X chromosome causes Turner syndrome and an extra X in a male causes Klinefelter syndrome. Other abnormalities are caused by extra or missing pieces of chromosomes. Fragile X syndrome is a sex-linked disease, causing mental retardation in males.

Chromosome material may also be rearranged, such as the end of chromosome 1 moved to the end of chromosome 3. This is called a chromosomal translocation. If no material is added or deleted in the exchange, a person may not be affected. Such an exchange, however, can cause infertility or abnormalities if passed to children.

Evaluation of a couple's infertility or repeated miscarriages will include blood studies of both to check for a chromosome translocation. Many chromosome abnormalities are incompatible with life. Fetuses with these abnormalities often spontaneously abort during the first trimester. Cells from a fetus that died before birth can be studied to look for chromosome abnormalities that may have caused the death.

CANCER DIAGNOSIS AND PROGNOSIS. Certain cancers, particularly leukemia and lymphoma, are associated with changes in chromosomes: extra or missing complete chromosomes, extra or missing portions of chromosomes, or exchanges of material (translocations) between chromosomes. Studies show that the locations of the chromosome breaks are at locations of tumor suppressor genes or oncogenes.

Chromosome analysis on cells from blood, bone marrow, or a solid tumor help to diagnose certain kinds of leukemia and lymphoma and often help predict how well a person will respond to treatment. After treatment has begun, periodic monitoring of these chromosome changes in the blood and bone marrow gives a physician information as to the effectiveness of the treatment.

A well-known chromosome rearrangement is found in chronic myelogenous leukemia. This leukemia is associated with an exchange of material between chromosomes 9 and 22. The resulting smaller chromosome 22 is called the Philadelphia chromosome.

Preparation

Most tests for genetic diseases of children and adults are done using blood. To collect the 5-10 mL of blood needed, a health care worker draws blood from a vein in the inner elbow region. Collection of the sample takes only a few minutes.

Prenatal testing is done either on amniotic fluid or a chorionic villus sampling. To collect amniotic fluid, a physician performs a procedure called amniocentesis. An ultrasound is done to find the baby's position and an area filled with amniotic fluid. The physician inserts a needle through the woman's skin and the wall of her uterus and withdraws 5-10 mL of amniotic fluid. Placental tissue for a chorionic villus sampling is taken through the cervix. Each procedure takes approximately 30 minutes.

Bone marrow is used for chromosome analysis in a person with leukemia or lymphoma. The person is given local anesthesia. Then the physician inserts a needle through the skin and into the bone (usually the hip bone). A sample (0.5 to 2.0 2 mL) of bone marrow is withdrawn. This procedure takes approximately 30 minutes.

Aftercare

After blood collection, a person may feel discomfort or bruising at the puncture site or may become dizzy or faint. Pressure to the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve discomfort.

The chorionic villi sampling, amniocentesis and bone marrow procedures are all done under a physician's supervision. A person to be tested is asked to rest after the procedure and is watched for weakness and signs of bleeding.

Complications

Collection of amniotic fluid and chorionic villi share the risks of miscarriage, infection, and bleeding. The risks are higher for the chorionic villi sampling. Because of the potential risks for miscarriage, 0.5% following the amniocentesis and 1% following chorionic villi sampling procedure, both of these prenatal tests are offered to couples, but are not required. A woman should tell her physician immediately if she has cramping, bleeding, fluid loss, an increased temperature, or a change in the baby's movement following either of these procedures.

After bone marrow collection, the puncture site may become tender and a person's temperature may rise. These are signs of a possible infection.

Genetic testing involves other nonphysical risks. Many people fear the possible loss of privacy about personal health information. Results of genetic tests may be reported to insurance companies and affect a person's insurability. Some people pay out-of-pocket for genetic tests to avoid this possibility. Laws have been proposed to deal with this problem. Other family members may be affected by the results of a person's genetic test. Privacy of the person tested and the family members affected is a consideration when deciding to have a test and to share the results.

A positive result carries a psychological burden, especially if the test indicates a person will develop a disease, such as Huntington's chorea. The news that a person may be susceptible to a specific kind of cancer, while it may encourage positive preventive measures, may also negatively shadow many future decisions and activities.

A genetic test result may also be inconclusive, meaning no definitive result can be given to the individual or family. This may cause an individual to feel more anxious and frustrated and experience psychological difficulties.

Prior to undergoing genetic testing, genetic counselors should inform individuals to be tested about the likelihood that the test could miss a mutation or abnormality.

Results

Normal results

A normal result for chromosome analysis is 46, XX or 46, XY. This means there are 46 chromosomes (including two X chromosomes for a female or one X and one Y for a male) with no structural abnormalities. A normal result for a direct DNA mutation analysis or linkage study is the absence of gene mutations.

There can be some benefits from genetic testing when an individual tested is not found to carry a genetic mutation. Those who learn with great certainty they are no longer at risk for a genetic disease may choose not to undergo prophylactic therapies and may feel less anxious and relieved.

Abnormal results

An abnormal chromosome analysis report will include the total number of chromosomes and will identify the abnormality found. Tests for gene mutations will report the mutations found.

There are many ethical issues to consider with an abnormal prenatal test result. Many of the diseases tested for during a pregnancy cannot be treated or cured. In addition, some diseases tested for during pregnancy may have a late-onset of symptoms or have minimal effects on an affected individual.

Before making decisions based on an abnormal test result, a person should meet again with a genetic counselor to fully understand the meaning of the results, learn what options are available based on the test result, and what are the risks and benefits of each of those options.

Health care team roles

A family physician or obstetrician often makes an initial recommendation for genetic counseling. A physician specially training in the technique will perform bone marrow aspiration, amniocentesis, or chorionic villus sampling. A nurse or phlebotomist usually collects blood samples. A cytogenetic technologist or clinical laboratory scientist/medical technologist will perform the DNA test depending upon the type of testing requested. A pathologist or geneticist processes and interprets findings of tests. Genetic counselors interpret test results and discuss options. Members of the clergy often assist people who have been tested to make decisions based on test results.

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KEY TERMS

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Autosomal disease—A disease caused by a gene located on chromosomes 1 through 22.

Carrier—A person who has a disease-causing gene but does not show symptoms of that disease.

Chromosome—Structures made up of DNA, on which genes are located.

DNA (Deoxyribonucleic acid)—A long molecule made up of two strands of material coiled around each other in a unique double helix. DNA contains the blueprint for all of a person's traits.

Dominant gene—A gene, whose presence as a single copy, controls the expression of a trait.

Enzyme—A protein produced in a cell.

Gene—A grouping of base pairs that give instruction for a specific trait.

Karyotype—Visual comparison of chromosomes arranged side-by-side with their partner in ascending numerical order, from largest to smallest.

Mutation—Any change in the sequence of DNA.

Positive predictive value (PPV)—The probability that a person with a positive test result has, or will develop a disease or condition.

Recessive gene—A gene that must be present in both copies of the gene pair to allow the expression of a trait.

Sensitivity—The likelihood that a negative test means a person will not have the disease or a mutation.

Sex-linked disorder—A disorder caused by a gene located on a sex chromosome, usually the X chromosome.

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L. Fleming Fallon, Jr., MD, DrPH