Genetic testing is a medical evaluation that indicates whether a person’s cells contain genetic material associated with an inherited disorder. The material consists of a particular form of a gene. Genes are chemically coded sets of biological information within every cell. Each form of a gene carries a particular set of instructions.
Genetic testing focuses on identifying disease-related forms of genes and developing methods to detect them. Many such tests are conducted by examining the genetic material inside cells obtained from blood samples, from inside a person’s cheeks, or in hair roots. Another approach involves determining whether a gene’s product—that is, a protein—is normal. Genetic testing has become an extremely active field of medical research.
How genes carry information. Genes code information in particular lengths of a chemical called DNA (deoxyribonucleic acid). DNA is made up of four types of simpler chemicals called bases. The four bases are adenine (A), cytosine (C), guanine (G), and thymine (T). DNA is tightly coiled into microscopic structures called chromosomes. People have 23 pairs of chromosomes within the nucleus of every cell except egg and sperm cells, which have only 1 chromosome of each pair. People inherit one chromosome of each pair from their mother and one from their father. Scientists estimate that human chromosomes contain 20,000 to 30,000 genes. The order in which the bases A, C, G, and T are arranged determines the information coded in each gene. The position on a chromosome where a gene normally occurs is called its locus «LOH kuhs», from the Latin word for place.
Any form of a gene that can occur in a particular locus is called an allele «uh LEEL». Some genes have as many as several hundred different alleles. In general, people inherit two alleles for each gene—one in the set of chromosomes that they receive from their mother and one from their father. In rare cases, both alleles in a particular locus may come from one parent.
Strictly speaking, genetic testing detects alleles, not genes. Although people commonly refer to “testing for genes,” this description is inexact. Everyone has some form of the gene for a particular characteristic at that locus. Genetic tests establish whether an individual carries an abnormal allele associated with a particular disorder. Abnormal alleles arise as a result of mutation, a random process that alters the order of bases in a gene.
Scientists often use the example of hemoglobin, the molecule in red blood cells that carries oxygen, to illustrate the relationship among genes, alleles, and DNA. Everyone has genes for hemoglobin at the hemoglobin locus, and there are several different alleles for it. One of the hemoglobin alleles, called hemoglobin S or sickle hemoglobin, is associated with a disease called sickle cell anemia. In this disorder, normally round red blood cells twist into crescent shapes as hemoglobin S releases oxygen. The deformed cells block tiny blood vessels and cause serious symptoms. The allele for hemoglobin S differs from other alleles by only one base in one of the sequences of DNA that codes for hemoglobin. See Sickle cell anemia.
Genes associated with disease. The importance of genes in determining particular diseases or other characteristics varies. A few thousand disorders occur as a result of one or more abnormal alleles in a single gene. More often, the relationship between genes and disease is complex. Many genetic diseases involve alleles for several genes. In many disorders, environmental factors, such as diet, exercise, or smoking, also play a role.
Single-gene diseases. Most single-gene diseases are rare, and many cause serious disability, severe pain, or even early death. Scientists classify single-gene diseases as dominant or recessive. Dominant diseases appear in an individual who has inherited an abnormal allele from only one parent. Inheriting a healthy allele from the other parent does not prevent the disease from occurring.
Many dominant diseases are fatal in childhood, so affected individuals do not live long enough to pass the disease on to future generations. But a few dominant diseases do not appear until adulthood, at a time when many affected individuals may have already had children. One such condition is a fatal nerve disorder called Huntington’s disease, which typically appears when people are 35 to 40 years old. Children of a person with Huntington’s disease have a 50 percent chance of inheriting the affected parent’s abnormal allele.
Most single-gene disorders are recessive. These diseases occur only in individuals who have inherited an abnormal allele from both parents. A person who has only one abnormal allele for these diseases is called a carrier and usually experiences few or no symptoms. Examples of recessive single-gene diseases in which carriers have few or no symptoms include sickle cell anemia and cystic fibrosis, a fatal lung and digestive disorder.
Genetic inheritance of hemophilia
Certain recessive conditions are called X-linked recessive disorders. Alleles for these disorders are carried on the X chromosome, one of two chromosomes that determines sex. The other sex-determining chromosome is called the Y chromosome. Males are XY and females are XX. A male (XY) who inherits an abnormal recessive allele on the X chromosome will lack a normal allele on his Y chromosome, and will develop the disorder associated with the abnormality. But females (XX) who inherit an abnormal allele on one X chromosome usually have a normal allele on the other, so will not develop the associated disorder. A blood clotting disorder called hemophilia is one example of an X-linked recessive disease.
Single-gene diseases that always occur when people have the one or two alleles involved are called completely penetrant. These disorders are also called Mendelian, because they follow predictable patterns of inheritance that Austrian monk Gregor Mendel observed in his experiments with garden peas in the 1800’s.
A number of tests are available to detect single-gene, completely penetrant diseases. Such tests can predict conclusively whether a disease will occur. But the tests cannot predict the severity of the condition, which may vary from one person or family to another. For example, blood tests can determine if parents-to-be carry the abnormal allele for cystic fibrosis. If both parents are carriers, their children will have 1 chance in 4 of having cystic fibrosis. Parents who discover that they are both carriers may choose to have further genetic tests performed prior to birth on any children that they conceive. If these tests show that an unborn child has the disorder, the parents may choose to end the pregnancy.
Disorders involving more than one gene. Most genetic diseases involve more than one gene. Many such disorders are also influenced by environmental factors. For example, certain alleles at a locus called BRCA1 greatly increase the likelihood—but do not guarantee—that a woman will develop breast cancer. Such an allele is called incompletely penetrant. Inheriting such an allele from one parent is sufficient to increase risk.
Tests are available for some alleles—including those at the BRCA1 locus—that increase the risk of disease. But the results of such a test may be hard to interpret. One difficulty is that not everyone who has one such allele gets the disease. Further, people who have one such allele but have few or no relatives with the disease may get the disease less often than do people who have many family members with the condition.
Promises and challenges of genetic testing. Genetic testing has caused excitement among scientists and patients because it offers the possibility of predicting future health problems. In some cases, knowing that a person carries an abnormal allele may enable the individual to avoid the disorder associated with the allele. Such measures as careful medical supervision and lifestyle changes may help some people escape serious illness. Scientists also hope that future discoveries may enable them to develop treatments that will correct genetic errors directly in abnormal DNA.
But genetic testing also involves medical limitations and stirs social concerns. One important medical issue is that genetic tests cannot always accurately predict future disease. Further, no treatment yet exists for some of the disorders for which genetic tests are available. Such situations may burden adults with knowledge of future untreatable disease or confront parents of unborn children with difficult choices about whether to end a pregnancy.
Privacy of genetic testing is a social issue that concerns many scientists and policymakers. They fear that insurers will deny health insurance to healthy individuals whose test results indicate a high risk or certainty of future illness. Some states of the United States have enacted laws forbidding discrimination in health insurance based on genetic testing.
Genetic testing also stirs fears that results will be used for purposes that most people find unacceptable, such as eugenics. Eugenics is the practice of attempting to control human breeding to encourage “desirable” traits or to prevent “undesirable” ones. See Eugenics.
Medical experts urge that genetic tests never be performed without a patient’s informed consent. Informed consent means that health professionals have clearly explained the risk and benefits, and that the patient has agreed to the procedure.