Genetics and Health - Genetic Testing And Human Reproduction

There are thousands of genetic diseases, such as sickle cell anemia, cystic fibrosis, and Tay-Sachs disease, that may be passed from one generation to the next. Numerous tests have been developed to help screen parents at risk of passing on genetic disease to their children as well as to identify embryos, fetuses, and newborns that suffer from genetic diseases.

Carrier Identification

Carrier identification is the term for genetic testing to determine whether a healthy individual has a gene that may cause disease if passed on to his or her offspring. It is usually performed on people considered to be at higher than average risk, such as those of Ashkenazi Jewish descent, who have a one in thirty chance of being Tay-Sachs disease carriers (in other populations the risk is about one in three hundred). Testing is necessary because many carriers have just one copy of a gene for an autosomal recessive trait and are unaffected by the trait or disorder. Only someone with two copies of the gene will actually have the disorder. So while it is widely assumed that everyone is an unaffected carrier of at least one autosomal recessive gene, it only presents a problem in terms of inheritance when two parents have the same recessive disorder gene (or both are carriers). In this instance the offspring would each have a one in four chance of receiving a defective copy of the gene from each parent and developing the disorder.

Another example of carrier identification is the test for a deletion in the dystrophin gene, which results in Duchenne muscular dystrophy. Carriers may avoid having an affected child by preventing pregnancy or by undergoing prenatal testing for Duchenne muscular dystrophy, with the option of ending the pregnancy if the fetus is found to be affected.

Using genetic testing to detect carriers poses some challenges. Typically, a carrier has inherited a mutant gene from one parent and a normal gene from another parent. If, however, the carrier harbors a mutation that is only found in germ cells (the sperm or eggs), and only in some of these germ cells, then conventional genetic testing, which is performed on white blood cells, will miss the mutation.

Preimplantation Genetic Diagnosis

Preimplantation genetic diagnosis (PGD) is a newer genetic test that enables parents undergoing in vitro fertilization (fertilization that takes place outside the body) to screen an embryo for specific genetic mutations when it is no larger than six or eight cells and before it is implanted in the uterus to grow and develop. One advantage of PGD is that it can screen any congenital disorder for which the causative gene is known and may be used by couples that wish to avoid traditional prenatal diagnosis and the possibility of termination of pregnancy.

Prenatal Testing

Prenatal genetic testing enables physicians to diagnose diseases in the fetus. Most genetic tests examine blood or other tissue from the mother to detect abnormalities. An example of a blood test is the triple marker screen. This test measures levels of alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol, and can identify some birth defects such as Down syndrome and neural tube defects. (Two of the most common neural tube defects are anencephaly—absence of the majority of the brain—and spina bifida—incomplete development of the back and spine). Triple marker screen results are usually available within several days, and women with abnormal results are often advised to undergo additional diagnostic testing such as chorionic villus sampling (CVS), amniocentesis, or percutaneous umbilical blood sampling (withdrawing blood from the umbilical cord).

CVS enables obstetricians and perinatologists (physicians specializing in evaluation and care of high-risk expectant mothers and infants) to assess the progress of pregnancy during the first trimester (the first three months). The optimal time for CVS is between ten and eleven and a half weeks of gestation. The cells obtained via CVS are examined in the laboratory for indications of genetic disorders such as cystic fibrosis, Down syndrome, Tay-Sachs disease, and thalassemia, and the results of testing are available within seven to fourteen days. CVS provides the same diagnostic information as amniocentesis; however, the risks (miscarriage, infection, vaginal bleeding, and birth defects) associated with CVS are slightly higher. Approximately one in every one hundred pregnancies is miscarried as a result of CVS.

Amniocentesis involves taking a sample of the fluid that surrounds the fetus in the uterus for chromosome analysis. An amniocentesis is usually performed at fifteen to eighteen weeks of gestation, although it can be done as early as twelve weeks. Like CVS, amniocentesis samples and analyzes cells derived from the baby to enable parents to learn of chromosomal abnormalities, as well as the gender of the unborn child, about two weeks after the test is performed. The risk of miscarriage—about one in every two hundred pregnancies—resulting from amniocentesis is lower than the risk associated with CVS.

Using samples of genetic material obtained from amniocentesis or CVS, physicians can detect disease in an unborn child. Down syndrome (also known as trisomy 21, because it is caused by an extra copy of chromosome 21) is the genetic disease most often identified using this technique. Down syndrome is rarely inherited; most cases result from an error in the formation of the ovum (egg) or sperm, leading to the inclusion of an extra chromosome 21 at conception. As with prenatal diagnosis for most inherited genetic diseases, this use of genetic testing is focused on reproductive decision making.

The most invasive prenatal procedure for genetic testing is percutaneous umbilical blood sampling. Under high-resolution ultrasound, a sample of fetal blood is removed from the umbilical cord. This test can be performed from approximately sixteen weeks gestation to term. Percutaneous umbilical blood sampling poses the greatest risk to the unborn child—one in fifty miscarriages occur as a result of this procedure. It is used when a diagnosis must be made quickly. For example, when an expectant mother is exposed to an infectious agent with the potential to produce birth defects, it may be used to examine fetal blood for the presence of infection.