This article discusses genetic testing, that is, testing that looks at a person's genetic makeup for a variety of reasons. An increasing number of genetic tests are becoming available as a result of recent and rapid advances in biomedical research. It has been said that genetic testing may revolutionize the way many diseases are diagnosed. Genetic testing does not just help a physician diagnose disease, however. There are a number of different reasons genetic tests are performed. This article briefly discusses each of these reasons for testing but focuses on the medical aspects of genetic testing. However, it is helpful to first understand the basics of human genetics. Continue reading for an overview of the basics.
The Universe of Genetic Testing
The total of an individual's genetic information is called their genome. The genome consists of structures called chromosomes that are composed of very long double strands of DNA. Each human cell contains 23 pairs of chromosomes. One-half of each pair is inherited from an individual's mother and the other half of the pair is inherited from an individual's father. Twenty-two of the 23 pairs of chromosomes are called autosomes; the other pair is composed of the X and Y sex chromosomes. The sex chromosomes determine a person's sex; normal males have one X and one Y chromosome while normal females have two X chromosomes.
Chromosomes are located in the part of the cell called the nucleus. The long, double strand of DNA (sometimes called "nuclear DNA") contained in each chromosome is organized into many subunits of genetic information, with each subunit referred to as a gene. Genes are made up of nucleotides, which are composed of phosphates, a sugar, and a nitrogen-containing base. There are four bases in DNA: adenine, guanine, thymine, and cytosine. It is the difference in the arrangement of these bases on each strand of DNA that leads to the uniqueness of each person's genetic makeup. The arrangement of the bases in each gene is used to produce RNA, which in turn produces a protein. There are some 30,000-50,000 genes in a human genome, and expression of these genes leads to the production of a large number of proteins that make up our bodies.
There is also a tiny bit of DNA that is not located in a cell's nucleus but in the mitochondria that are located in the cytoplasm of every cell. Mitochrondria are very important cellular structures involved in the basic functioning of cells, and they contain their own circular piece of DNA. This DNA is called "extra-nuclear DNA" or more simply "mitochrondrial DNA," and it in part makes the proteins that are needed by the mitochrondria to function properly.
A person's genotype is their genetic identity, the specific combination of genes that they have in their cells.
This does not show in terms of outward appearances. Observable traits or characteristics, such as hair color or height, are considered a person's phenotype. Phenotype is the physical expression of the genotype. People's phenotypes are different because their genotypes are different. Although human genotypes are alike in many ways, small differences make us unique beings in both appearance and genetic makeup. These differences are called polymorphisms.
Genetic polymorphisms in both nuclear DNA and mitochrondrial DNA help to identify us as individuals. Sometimes, but not always, these differences in our genotype are related to disease or to the inability to metabolize or break down drugs normally. These kinds of polymorphisms are called genetic variations, or mutations, and they are either inherited or they can occur spontaneously. Some of these genetic variations occurred over time in an attempt by our bodies to protect us from disease. These variations will be discussed under the specific Conditions/Diseases that have a genetic component, such as cystic fibrosis. Sometimes only one nucleotide in a gene is different, and this is referred to as a "single-nucleotide polymorphism." This will be explained in greater detail in the section on Clinical Genetic Testing. It is important to remember that not all genetic variations, or mutations, are bad or lead to disease.
Patterns of Inheritance
There are several ways in which an individual's polymorphisms are inherited. These are called "patterns of inheritance" and result in the transmission of a polymorphism or mutation from one generation to the next.
One pattern is referred to as autosomal dominant, in which the transmission of a single copy of a gene on one of the autosomal chromosomes is sufficient to cause a certain trait to appear (such as eye color or a specific disease). The gene may be inherited from either an individual's mother or father. Individuals with an autosomal dominant trait or disease have a 50-50 chance of passing the polymorphic gene on to their children. Examples of autosomal traits are brown eyes and the ability to roll one's tongue; examples of autosomal dominant diseases are familial hypercholesterolemia and Huntington disease.
An unusual concept of dominant genes is referred to as co-dominance, in which the genes on both chromosomes are expressed together. An example of this is the blood type AB, in which the A antigen protein and the B antigen protein are both located on an individual's red blood cells.
A second pattern of inheritance is termed autosomal recessive and requires inheritance of two genetic variant copies of the same gene, one copy being inherited from an individual's mother and the second copy being inherited from an individual's father, for the trait to appear or the disease to develop. If the individual inherits only one of the variant genes, he or she will not develop the disease but instead will be a carrier, much like his or her parent, and can in turn pass the variant gene on to his or her children. An example of an autosomal recessive trait would be blue eyes; examples of autosomal recessive diseases include cystic fibrosis, sickle cell anemia, and hemochromatosis.
There are also patterns of inheritance in which the variant gene resides on either the X or Y sex chromosome and these are referred to as sex-linked patterns of inheritance. With X-linked recessive diseases, a female carries the abnormal gene on one of her two X chromosomes, but because she possesses one normal copy of the gene, she is not affected. However, since males have only one X chromosome, a single abnormal copy of the recessive gene on his X chromosome (inherited from his mother) is sufficient to cause the disease. Examples include Duchenne's muscular dystrophy and hemophilia. If a disease is X-linked dominant, a single abnormal gene on the X chromosome can cause that disease to develop so that a female is affected and the condition is often lethal in males. This is a rare pattern of inheritance.
It is interesting to note that mitochondrial DNA (or "extra-nuclear DNA") is inherited only from our mothers. This is referred to as a "maternal mode" of inheritance.
There are many factors that may obscure or complicate inheritance patterns. These factors in turn affect the way a gene is inherited or expressed.
Clinical Genetic Testing
Clinical genetic testing refers to the laboratory analysis of DNA or RNA to aid in the diagnosis of disease. It is very important to understand that clinical genetic testing is quite different than other types of laboratory tests. Genetic testing is unique in that it can provide definitive diagnosis as well as help predict the likelihood of developing a particular disease before symptoms even appear; it can tell if a person is carrying a specific gene that could be passed on to his or her children; it can inform as to whether some treatments will work before a patient starts therapy. These are definite advantages. However, there are also some qualities of genetic testing that should be carefully thought out and perhaps discussed with a genetic counselor before undergoing any test. These aspects are reviewed in the section below titled Pros and Cons of Genetic Testing. In an era of patient responsibility, it is important that you be educated in these matters to fully appreciate the value as well as the drawbacks of genetic testing.
Testing Genetic Material
Testing of genetic material is performed on a variety of specimens including blood, urine, saliva, stool, body tissues, bone, or hair. Cells in these samples are isolated and the nucleic acids (DNA or sometimes RNA) within them is extracted and examined for possible mutations or alterations. Looking at small portions of the DNA within a gene requires specialized and specific laboratory testing. This is done to pinpoint the exact location of genetic errors. This section will focus on the examination of a person's genes to look for the one(s) responsible for a particular disease.
There are four basic reasons that genetic material is tested for clinical reasons. Presymptomatic testing identifies the presence of variant genes that cause disease even if the physical abnormalities associated with the disease are not yet present in an individual. Diagnostic genetic testing is performed on a symptomatic individual with symptoms sufficiently suggestive of a genetic disorder. This assists the individual’s physician in making a clear diagnosis.
Testing of genetic material can also be performed as a prenatal screening tool to assess whether two individuals who wish to become parents have an autosomal or X-linked recessive gene that, when combined in a child, will produce a serious disorder in that child. This type of genetic testing is referred to as carrier screening. Fetuses developing in the uterus can also have their genetic material tested to assess their health status if it is thought to be in jeopardy.
To test DNA for medical reasons, some type of cellular material is required. This material can come from blood, urine, saliva, body tissues, bone marrow, hair, etc. The material can be submitted in a tube, on a swab, in a container, or frozen. If the test requires RNA, the same materials can be used. Once received in the laboratory, the cells are removed from the substance they are in, broken apart, and the DNA in the nuclei is isolated and extracted.
The laboratory professionals who perform and interpret these tests are specially trained physicians and scientists. The extracted DNA is manipulated in different ways in order for the molecular pathologist or genetic technologist to see what might be missing or mutated in such a way as to cause disease. One type of manipulation is "cutting" the DNA into small pieces using special enzymes. These small pieces are much easier to test than the long strands of uncut DNA and they contain the genes of interest. Another manipulation is to apply the extracted and cut DNA to an agarose gel, apply an electrical field to the gel, and see how the DNA moves on the gel. This can indicate differences in the size of the pieces of the cut DNA that might be caused by specific mutations.
Other manipulations to DNA include amplification, sequencing, or a special procedure called hybridization. When the results of these tests are examined and compared with results from a normal person, it is possible to see differences in the genes that might cause a disease.
Specific Genetic Diseases
There are many diseases that are now thought to be caused by alterations in DNA. These alterations can either be inherited or can occur spontaneously. Several things can go wrong with the genes that make up the DNA, resulting in diseases. The section below discusses what can happen to DNA, and specifically to genes, that might lead to a disease.
Genetic Variation and Mutation
All genetic variations or polymorphisms originate from the process of mutation. Genetic variations occur sometimes during the process of somatic cell division (mitosis). Other genetic variations can occur during meiosis, the cycle of division that a sperm cell or an ovum goes through. Some variations are passed along through the generations, adding more and more changes over the years. Sometimes these mutations lead to disease; other times there is no noticeable effect. Genetic variations can be classified into different categories: stable genetic variations, unstable genetic variations, silent genetic variations, and other types.
Stable genetic variations are caused by specific changes in single nucleotides. These changes are called single nucleotide polymorphisms or SNPs and can include:
- Substitutions, in which one nucleotide is replaced by another
- Deletions, in which a single nucleotide is lost
- Insertions, in which one or more nucleotides are inserted into a gene
If the SNP causes a new amino acid to be made, it is called a "missense mutation." An example of this is in sickle cell anemia, in which one nucleotide is substituted for another. The genetic variation in the gene causes a different amino acid to be added to a protein, resulting in a protein that doesn't do its job properly and causes cells to form sickle shapes and not carry oxygen.
Unstable genetic variations occur when a nucleotide sequence repeats itself over and over. This is called a "repeat" and is usually normal; however, if the number of repeats increases too greatly, it is called an "expanded repeat" and has been found to be the cause of many genetic disorders. An example of a disease caused by an expanded repeat is Huntington disease, a severe disorder of a part of the brain that is marked by dementia, hydrocephalus, and unusual movements.
Silent genetic variations are those mutations or changes in a gene that do not change the protein product of the gene. These mutations rarely result in a disease.
Other types of variations occur when an entire gene is duplicated somewhere in a person's genome. When this occurs, extra copies of the gene are present and make extra protein product. This is seen in a disorder that effects peripheral nerves and is called Charcot-Marie-Tooth disease type 1. Some variations occur in a special part of the gene that controls when DNA is copied to RNA. When the timing of protein production is thrown off, it results in decreased protein production. Other variations include a defect in a gene that makes a protein that serves to repair broken DNA in our cells. This variation can result in many types of diseases, including colorectal cancer and a skin disease called xeroderma pigmentosum.
Testing for Products of Genetic Expression
Many inherited disorders are identified indirectly by examining abnormalities in the genetic end products (proteins or metabolites) that are present in abnormal forms or quantities. As a reminder, genes code for the production of thousands of proteins and, if there is an error in the code, changes can occur in the production of those proteins. So, rather than detecting the problem in the gene, some types of testing look for unusual findings related to the pertinent proteins, such as their absence.
An example of testing for genetic products includes those widely used to screen newborns for a variety of disorders. For example, newborns are tested for phenylketonuria (PKU), an inherited autosomal recessive metabolic disorder caused by a variation in a gene that makes a special enzyme that breaks down phenylalanine, an amino acid. When too much of this substance builds up in blood, it can lead to mental retardation if not treated early in life with a special, restricted diet. The test uses a blood sample from a baby's heel to look for the presence of extra phenylalanine, rather than looking for the mutated gene itself. Other examples include blood tests for congenital hypothyroidism, diagnosed by low blood levels or absence of thyroid hormone, and congenital adrenal hyperplasia, a genetic disease that causes the hormone cortisol to be decreased in blood. Frequently, abnormal blood screening tests in the newborn may be augmented by genetic testing when appropriate (in cystic fibrosis, for example).
There have been cases regarding individuals who are given a certain therapeutic drug to treat symptoms or to keep symptoms from occurring in which the individual has a very violent reaction to the drug or feels no affect whatsoever. Many times this happens because of the genetic makeup of the individual. The study of this phenomenon is called "pharmacogenomics" or "pharmacogenetics."
As an example, a woman had surgery to remove a tumor and was given codeine as a pain reliever. Although she was doing well after the surgery, as soon as she began treatment with codeine she developed a full-body rash, difficulty breathing, and an irregular heartbeat. When she was taken off the codeine, her reaction disappeared. Upon further study, it was found that she lacked the enzyme in her blood that metabolized (broke it down into different components) the codeine into morphine and other substances, so she was essentially being overdosed with codeine. The lack of the enzyme was directly related to a variation in the gene that produced it. This genetic variation is a polymorphism between normal individuals and those who carry it. Sometimes these polymorphisms can cause a very serious reaction in an individual that could lead to death.
In some cases, individuals "hypermetabolize" drugs. This occurs when there is too much of an enzyme present that breaks down the helpful drug too quickly, leading to a lack of response to the drug. This can happen when too many copies of the gene are made and too much enzyme is produced. In other cases, the special receptor that the drug binds to on cells or tissues is missing, again because of a variation in the gene that makes the receptor protein. When there is no receptor to bind the drug, the drug may not have any affect on the cells or tissues that it should.
Genetic testing to determine the polymorphisms that play a role in our response to a drug is typical of basic genetic analyses. DNA is removed from cells, manipulated to find a specific area on a specific chromosome, and compared to "normal" DNA. In this way, genetic variations can be seen that may play a role in the over- or under-responsiveness to a therapeutic drug. This testing can also determine an individual's resistance or sensitivity to the effectiveness of certain drugs used in viral therapy (HIV or hepatitis C drugs, for example).
There are many, many enzymes in our blood that act to metabolize or break down specific drugs, allowing them to be excreted in urine or by other means. At present, there are comprehensive testing programs in place that can give us an overall picture of our specific genetic variations that may cause us to be unresponsive or over-responsive to a therapeutic drug.
For more information on this subject, see our article Pharmacogenetic Tests.
Identity testing is sometimes referred to as "DNA testing," a term most frequently used in relation to criminal investigations. "DNA testing" is an unfortunate misnomer as all types of genetic analysis, whether for disease diagnosis or for tissue typing, involves assessment of DNA or RNA.
Identity testing focuses on the identification of an individual through the analysis of either nuclear or mitochondrial DNA extracted from some material: blood, tissue, hair, bone, etc. Any material that contains cells with nuclei can be used for nuclear DNA extraction and eventual identity testing. Mitochondrial DNA, which is "extra-nuclear," is used when a sample is severely degraded or if only hair shafts with no attached cells are available.
Increasingly, identity testing is used to identify a suspect in a criminal investigation by comparing the DNA found at a crime scene to that of the suspected individual. If a suspected individual is convicted of the crime, his or her DNA polymorphisms are put into a data bank system that is accessible by law enforcement officials. This system is referred to as CODIS or "Combined DNA Index System." This system has helped to solve many crimes and also to clear those wrongfully accused of a crime.
Other uses of identity testing are to identify individuals whose identity cannot be distinguished by other means, as with decomposed bodies. In this type of genetic testing, specific parts of DNA are examined for polymorphisms (differences) that are unique to the individual. These parts of the DNA strand are referred to as microsatellites or minisatellites and are composed of repeated subunits of the DNA strand. Sometimes these repeated units are called short tandem repeats (STRs) or variable number of tandem repeats (VNTRs). In forensics, these unique sequences are given the name "DNA fingerprint."
Other types of identity testing include the determination of an individual's parent or parents, often called "parentage testing," and identifying organ donors by using genetic testing for tissue transplantation, called "tissue typing."
For more on this, see the World of Forensic Laboratory Testing.
The primary goal of parentage testing is to identify the biological parent of a given child. It is done to determine an individual's parent or parents in, for example, cases of adoption or alleged paternity. This determination must be looked at very carefully and must identify the alleged parent with at least 99% certainty.
Many different types of laboratory tests can be done to assess parentage, including examination of red blood cell antigens (blood typing), examination of polymorphic serum protein genes, and assessment of short tandem repeats. The DNA testing techniques used are similar to those used in identity testing for a criminal investigation, that is, extracting DNA from cells and manipulating it in such a way as to be able to examine the individual uniqueness of it.
If, after testing multiple systems, the parent in dispute is not excluded as a possible parent, a mathematical estimate of the possibility that the tested person could be the biological parent must be calculated. This mathematical testing combines the results of the genetic tests with other "non-genetic events" (location of the alleged parent at the time of conception, phenotype of the parent and child, etc.) and results in a "parentage index." This index is a percentage of the likelihood of parentage. Results of these tests are admissible as evidence in court.
In the past, it was difficult to tell exactly whether an organ or tissue, such as a kidney, lung or bone marrow, was an exact match for the transplant between a donor and recipient. If it was not, a serious rejection reaction could sometimes occur between the recipient patient and the transplanted organ.
Basic laboratory testing for tissue transplantation involves mixing the white blood cells (leukocytes) from the donor (or the donor tissue) and the recipient together and observing whether an immune response occurs. Proliferation of a specific population of leukocytes signals the onset of an immune response and the likely rejection of the tissue by the recipient's body. Although this technique is still commonly used, analysis of the DNA in both the donor and the recipient (tissue typing) is used to diminish the likelihood of rejection in the case of tissue transplantation. In bone marrow transplants, DNA testing is done to determine whether the leukocytes and their precursors repopulating a recipient's bone marrow are his own or those of the donor.
A very specific set of genes is examined when DNA testing is used for tissue typing. On chromosome 6, a large set of genes called the "Major Histocompability Complex" or MHC, resides. These genes are very polymorphic (different) between individuals, and they code for the production of specific glycoprotein antigens located on the surface of many cells. It is these antigens that "recognize" our own organs and tissues from those of another individual. These antigens have the ability to begin an immune system response that results in organ or tissue rejection if the tissue looks foreign.
A distinct region within the MHC on chromosome 6 is used in the DNA analysis of tissue that could be used for transplantation. This region is called the human leukocyte antigen, or HLA-D, region, and sets of genes located there are further subdivided into HLA-DR, HLA-DQ, and HLA-DP depending on the type of glycoprotein antigen for which they code. Polymorphisms in these genes are carefully compared between donor and recipient to determine the appropriateness of the transplant.
The exact techniques used to test DNA for tissue typing are similar to those mentioned in the previous sections. DNA is extracted from donor and recipient cells, then manipulated and fragmented in such a way as to isolate a specific region on a chromosome and within a gene. The fragments are subjected to further analysis that allows for comparison of the polymorphisms in the HLA-DP between the donor's tissue and the recipient's blood. This careful analysis of genetic material results in fewer rejection reactions and the chance for a successful transplant.
Everyone has 23 pairs of chromosomes, 22 pairs of autosomes and one pair of sex chromosomes. The science that relates to the study of these chromosomes is referred to as "cytogenetics." Persons who look at chromosome preparations on slides are cytogenetic technologists or cytogeneticists. A trained cytogeneticist examines the number, shape, and staining pattern of these structures using special technologies. In this way, extra chromosomes, missing chromosomes, or rearranged chromosomes can be detected.
Studies of chromosomes begin with the extraction of whole chromosomes from the nuclei of cells. These chromosomes are then placed on glass slides, stained with special stains, and examined under a microscope. Sometimes, pictures are taken of the chromosomes on the slides, and the picture is cut into pieces so the chromosome pairs can be matched. Each chromosome pair is assigned a special number (from 1 to 22, then X and Y) that is based on their staining pattern and size.
There are many disorders that can be diagnosed by examining a person's whole chromosomes. Down syndrome, in which an individual has an extra chromosome 21, can be determined by cytogenetic studies. When there are three chromosomes in one group instead of a pair, it is referred to as a "trisomy." Missing chromosomes can also be detected, as in the case of Turner's syndrome, in which a female has only a single X chromosome. When there is only one chromosome instead of a pair, it is referred to as a "monosomy."
Abnormalities in chromosome structure are also observed with cytogenetic staining techniques. The Fragile X syndrome, the most common inherited cause of mental retardation, takes its name from the appearance of the stained X chromosome under a microscope. There is a site near the end of this chromosome that does not stain, indicating its fragility. The gene in the fragile region is important in making a special protein needed by developing brain cells.
Sometimes, pieces of a chromosome will break off and attach to another chromosome somewhere in a person's genome. When this happens, it is referred to as a "translocation." An example of a disease caused by a translocation would be chronic myelogenous leukemia (CML), in which a part of chromosome 9 breaks off and attaches itself to chromosome 22. Another example would be Burkitt lymphoma, in which a piece of chromosome 8 attaches to chromosome 14. These chromosomal translocations cause disease because the broken piece usually attaches to the new chromosome near a special gene that then becomes activated and produces tumor cells. Translocations can sometimes be seen under the microscope if a special stain is used (via conventional cytogenetic analysis).
A special technique called fluorescence in situ hybridization (FISH) can be used to view changes in chromosomes that result from genetic variations. An aberrant gene segment in a chromosome can be made to "light up" or fluoresce when it is bound by a special probe. Genetic changes in some cancers can be detected using this method. For instance, FISH is one of the methods used to determine increased copy number (amplification) of the gene ERBB2 (also known as HER2/neu) in breast cancer. There are many other applications of FISH technology as well, such as chromosome microdeletions, in which a certain part of a chromosome is completely missing. In this case, the chromosome segment will not fluoresce compared to a normal set of chromosomes.
Infectious Disease Testing
When we hear the term "infectious disease," we usually think of something that can infect us and cause a disease process to begin. That "something" can be a bacteria, virus, parasite, or fungus obtained from many different sources (other infected individuals, poor hygiene, transfusion with infected blood, shared needles between drug users, etc.). Disease-causing bacteria and viruses are known as infectious agents, and some of them can be quickly identified by using genetic testing techniques; however, common infectious agents, such as certain bacteria and viruses, are much less expensive to identify using standard laboratory methods that don't involve genetic testing techniques.
Bacteria are one-celled organisms that contain their own DNA and in some cases can cause serious disease. Even those bacteria that harmlessly live inside our bodies and are involved in beneficial chemical processes can become mutated under unusual conditions and cause us to be very sick. By isolating the DNA from bacteria, breaking it into small pieces, and amplifying them, the bacteria can be identified very quickly. Some of the bacteria that can be quickly identified using these genetic testing techniques include: Chlamydia trachomitis, which is an organism that causes the sexually-transmitted disease chlamydia; Neisseria gonorrhea, which causes gonorrhea, Borrelia burgdorferi which causes Lyme Disease, Legionella pneumophilia which causes Legionnaire's disease, Mycoplasma pneumoniae which leads to "walking pneumonia," Mycopbacterium tuberculosis which can cause tuberculosis, and Bordetella pertussis which causes whooping cough. Specimens that might contain these bacteria include urine, blood, sputum, cerebrospinal fluid, and others.
Viruses are unusual organisms that sometimes insert their DNA into a host's genome. The viral RNA or DNA utilizes the host's cells to produce proteins and make more viruses. Viruses such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are examples of RNA viruses.
Other disease-causing viruses that contain DNA instead of RNA include Herpes simplex virus, cytomegalovirus, Epstein-Barr virus, parvovirus, and varicella-zoster viruses. All of these viruses can be identified by first removing the suspected viral DNA or RNA from a patient specimen and then using it to provide a "fingerprint" of the suspected virus. Specimens usually include blood, cerebrospinal fluid, sputum, other body fluids, amniotic fluid, tissue, or bone marrow. Much of the testing on donor blood that will be used in a blood transfusion utilizes genetic testing to inspect the blood for viral contamination.
Determining how many copies of a virus' RNA are present in an individual's blood is another use of infectious disease genetic testing techniques. The number of copies present is typically referred to as the "viral load" or "viral burden." This testing is usually done after a drug therapy is initiated to assess whether it is working to remove or decrease the viral RNA load. The most common viral load tests are for HCV or HIV, and the tests require a sample of blood.
A parasite is a complex multi-cellular organism. Parasites usually infect an individual through the saliva of a biting insect, such as a mosquito, or through infected material. An example of a parasite that can be identified using genetic tests is Toxoplasma gondii, which can cause encephalitis or congenital infections that lead to severe damage of a fetus (fetal toxoplasmosis).
Pros and Cons of Genetic Testing
Genetic testing holds great potential for the future of medical care. It offers many benefits, including providing important information that can be used when making decisions about having a family and taking care of one's own health. However, there are also limitations. For this reason, it is important to understand the nature of genetic testing and the information that it can and can't provide. For example:
- Clinical genetic tests are not just descriptive as many laboratory tests are (such as describing the glucose level in your blood), but they are predictive as well. Predictive tests will not give a yes/no answer, but instead will tell what the chances are of developing a particular genetic condition. Such results are not definitive and may leave a person wondering what to do with those results, particularly if available treatments or therapies limit the course of action.
- A particular genetic test will only tell if there is specific genetic variant, or mutation; it cannot guarantee whether the disease will develop nor can the test provide information about other genetic diseases not being specifically looked for by that test.
- While the test may detect a particular problem gene, it cannot predict how severely the person carrying that gene will be affected. Again with cystic fibrosis, symptoms may be mild bronchial abnormalities or they may range to severe lung, pancreatic, and intestinal problems depending on the specific mutation present.
- Many genetic tests cannot detect all of the variations that can cause a particular disease. For instance, with genetic testing for cystic fibrosis, most genetic testing panels only look for the more common variants, not all of those that are associated with this disease.
- Many diseases are the result of an interaction between one's genes and one's environment. The way in which these interactions cause disease is not clearly understood. Examples of these diseases include coronary heart disease, type 2 diabetes, obesity, and Alzheimer disease.
- Legal issues, such as patient privacy, use of genetic testing to determine insurance coverage, and the use of archived patient samples are some of the broader social issues to be considered.
Because of these limitations, genetic test results can be a mixed blessing. An absolutely essential component of clinical genetics testing is giving your informed consent to do the tests and knowing what you want to do with the results of these tests. Know your legal rights as well. Make certain that your privacy is respected. Educate yourself about genetic tests, and talk to your medical provider if you think you should have genetic testing performed. This is especially important as more genetic testing becomes available directly to consumers. For more on this, listen to the following podcast from Clinical Chemistry and watch the NOVA program, Cracking Your Genetic Code.
Direct-to-Consumer Genotyping (Clinical Chemistry, August 2010)
It is also important to remember that genetic testing is different from other types of laboratory testing. Results of genetic tests may have implications not only for you the patient, but also for your family members, who may need to be tested as well. In addition, genetic education and counseling is often advised to help understand and cope with the results of genetic tests. Genetic counselors are trained professionals who can help those with family members who have a genetic disorder as well as those at risk to better understand the science behind inherited conditions. They can identify families at risk of certain genetic disorders and offer support and counseling as well as serve as patient advocates. For more information on genetic counselors and to find one near you, visit the National Society of Genetic Counselors web site.
The Future: Advances, Potential, Conclusions
With the completion of the Human Genome Project, we have learned that the word "normal" no longer has meaning when it comes to a person's genetic makeup. Genetic variations occur in great numbers in our genome (our total genetic makeup). We are all unique, not only in our personalities and appearance, but in our genotype as well.
Scientists continue to work on ways to better understand the structure of our genetic makeup, which could allow for important advances in the prevention and treatment of many diseases. There are promising new screening tests on the horizon, such as one for ovarian cancer or Alzheimer disease that researchers are trying to replicate in other disorders as well.
Gene therapy is an approach to treating potentially lethal and disabling diseases that are caused by single gene deficiencies. With specialized techniques, gene expression can be manipulated to correct the problem in the particular patient, although the correction will not be passed along to offspring of that patient. That is, corrections are made at the DNA molecule level to compensate for the abnormal gene so that the detrimental symptoms of the disease are not expressed in the patient. It is still highly experimental. Clinical trials are being conducted to see if this can be used to develop treatments for other diseases, including cancer, heart disease, and AIDS.
Further advances in technology and molecular biology lab techniques have led to a recent invention - the "gene chip" or microarray - which allows many genes to be examined together instead of one at a time as is done now. Using these gene chips, researchers can look for molecular indicators of disease even before the disease presents itself and the patient becomes symptomatic. Gene chips are still being developed and tested for clinical use.
Further advances in genetic testing will eventually replace older methods of predicting prognosis, helping to treat only those patients who will respond to therapy and by helping to guide further research into these therapies. Recent advances are also helping to increase our understanding of some complex cancers, such as multiple myeloma and lymphoma. Without a doubt, there will be more and more advances in genetic research that will impact the laboratory tests available to all patients for detection and treatment of a variety of diseases.