Genetic Testing

Genetic Testing
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. Indeed, a whole new field, genetic counseling, has grown up around the need to help patients understand the testing process.
The purposes of genetic tests vary. Some tests are used to confirm a preliminary diagnosis based on symptoms. But other genetic tests measure your risk of developing a disease, even if you are healthy now (presymptomatic testing), or whether you and your partner are at risk of having a child with a genetic disorder (carrier screening).
As the name suggests, a genetic test looks at your genes, which consist of DNA (deoxyribonucleic acid). Each gene contains a chemical message to produce a protein, which has a specific function in the body. Proteins are essential to life-they serve as building blocks for cells and tissues; they produce energy and act as messengers to make your body function. In addition to studying genes, genetic testing in a broader sense includes biochemical tests for the presence or absence of key proteins that signal aberrant gene function.
Some tests look at chromosomes for abnormalities such as an extra chromosome, or an incomplete or missing chromosome. Sometimes, pieces of chromosomes become switched, or transposed, so that a gene ends up in a location where it is permanently and inappropriately turned on or off. Chromosomes are made up of DNA with long chains of genes mixed with inactive DNA. Each of us has 46 chromosomes in the nucleus of each cell, half contributed by each parent. The genes on the chromosomes are responsible for directing our biological development and the activity of about 100 trillion cells in our bodies.
If something goes wrong with an essential protein, the consequences can be severe. For example, a protein called alpha-1 antitrypsin (AAT) clears the lungs of a caustic agent called neutrophil elastase. Those who cannot manufacture AAT because of a defect in the gene that produces the protein often develop emphysema and other complications.
Most genetic conditions come in the form of a mutation in a gene that alters the instructions for making the proteins. These mutations can lead to diseases ranging from those we think of as "genetic diseases," such as cystic fibrosis or AAT deficiency, to those we think of as degenerative diseases, such as cancer and heart disease. In the case of diseases like cancer, heart disease, asthma or diabetes, a combination of factors-some genetic, some related to environmental or lifestyle factors-may work together to trigger the disease.
It's possible to have a mutation, even one for a severe disease, such as cystic fibrosis (CF) and never even know it. That's because genes come in pairs-one contributed by your mother, one from your father. If you have a single such mutation, you are a healthy carrier of the disorder. Such disorders are called autosomal recessive. The unaltered gene in the pair retains the function. The disease becomes a possibility only if two carriers of the same recessive gene have a child. Each child of two carriers of the same disorder has a 25 percent chance of inheriting the disease. It is equally likely (a 25 percent chance) that both parents will contribute their unaltered genes, only the mutated genes, thus there is a 50 percent chance that the child will receive one functioning gene and one mutated gene-in other words, a 50 percent chance that the child will be a healthy carrier like the parents.
Some disorders, such as Huntington disease, are autosomal dominant. If a person has one mutated gene, its effects will cause the disease, even if the matching gene is normal. Thus, each child of a parent with Huntington disease has a 50 percent chance of inheriting the disease. Osteogenesis imperfecta, which causes brittle bones, is another example of a dominant disorder.
Autosomal means the gene is not found on one of the two sex chromosomes, X and Y. If each parent contributes an X chromosome, the child is a girl; an X and a Y chromosome makes the child a boy. Because girls have two copies of every sex-linked gene, they are less likely to have symptoms from X-linked genetic diseases than boys, who don't have a backup copy if an X-chromosome gene is mutated. Examples of X-linked diseases include forms of hemophilia and fragile X syndrome (the most common inherited cause of mental impairment).
Sometimes a genetic defect simply increases risk of developing a disease, often in conjunction with other genetic or environmental factors. For example, a mutation in a BRCA gene increases your risk of breast or ovarian cancer, but only if the companion unmutated copy of the gene in the same cell also acquires a mutation.
A normal copy of BRCA in a breast cell might acquire a mutation due to exposure to, say, an environmental toxin or radiation, or it might become mutated through a sporadic "mistake" during cell division and DNA replication. For a woman without a mutation, it would take two such events in one cell to trigger a BRCA-related breast cancer; for the woman who inherits a BRCA mutation, it takes only one. Other genes can also play a role. A woman with a BRCA mutation who also has a p53 (tumor suppressor gene) mutation would also be more vulnerable, and no doubt there are other genes whose malfunctioning in combination with a BRCA mutation can trigger breast cancer.
There also are other risk factors for breast cancer, such as high alcohol intake (more than two drinks per day), being overweight, not having children or having an early onset of menses.
Most women who develop breast cancer have no known risks for developing the disease other than being a woman or, in the case of an older woman, age. Age is a risk factor for developing many types of cancer.
An increased risk does not necessarily mean you have a disease or will develop it. Genetic test results can yield information to help you and your health care professionals better manage your health, or, in the case of prenatal testing, your baby's care.
Unfortunately, though, genetic tests do not always provide the clear answers you may want. Sometimes a mutation is found that is of uncertain significance. Also, many tests are designed to look for the most common disease-causing mutations. If you or your family has a unique mutation, these tests won't pick it up. Hence, many of the tests boast detection rates of 95 percent or more, but they are not perfect. If you have a strong family history of a disease and uncertain or negative test results, it may be better to play it safe and take added prevention measures as if you had tested positive for the mutation. A genetic counselor can provide guidance.
The Cost of Genetic Testing
The cost of a genetic test varies dramatically, ranging from about $50 to upwards of $2,000. The difference stems largely from the variation in labor intensity of different tests. Some tests look for a limited number of mutations (sometimes only one) known to cause a disease; others require sequencing of the entire gene. It's the difference between looking at a few particular frames of a film for defects and examining the entire reel.
The explosion of genetic research now taking place is expected to bring prices down and dramatically increase the number of tests available. In the coming years, tests may be available to predict your genetic risk of developing heart disease or diabetes, for example, and will help you and your health care professional develop specific strategies for prevention. Preventive efforts can include changing your lifestyle or perhaps taking certain medications, which may be tailored to your specific genetic profile, and early screening to head off the worst complications should you develop the disease.