Genetic Tests and Rare Genetic Mutations

The identification of several disease-causing genes, along with the improved understanding of human heredity, has led to the development of numerous tests for genetic conditions. The purpose of these genetic tests is to recognize the potential for a genetic condition in an early stage. The knowledge of genetic tests and rare gene mutations allows an early intervention that may lessen or prevent the development of a condition and also allows people to make informed choices about reproduction. Genetic testing includes newborn screening, heterozygote screening, presymptomatic diagnosis and prenatal testing.

Newborn screening is the testing for genetic disorders in newborn infants. In most US states and many other countries, it is required that newborn infants are tested for phenylketonuria and galactosemia. These metabolic diseases are caused by autosomal recessive alleles. If not treated at an early age, these conditions can lead to developmental delays, including intellectual or physical disability. But early intervention, through a modified diet, can prevent this. Testing is done by analyzing a drop of blood collected soon after birth. Additional diseases that can be identified by newborn screening are sickle-cell anemia and hypothyroidism.

Heterozygote screening is the testing of members of a population to identify heterozygous carriers of recessive disease-causing alleles. These people are perfectly healthy, but have the potential to produce children with a particular condition. A successful example of heterozygote screening is the testing for Tay-Sachs disease. This disease is a hundred times more frequent among Ashkenazi Jews than among the general population. A simple blood test is used to determine the carriers of the Tay-Sachs allele. If both parents are heterozygotes, one out of every four children runs the risk of developing the condition. Thanks to heterozygote screening there has been a significant decline in the number of children of Ashkenazi ancestry born with Tay-Sachs disease (fewer than ten children a year in the US).

Presymptomatic genetic tests are used to evaluate healthy people to determine whether they have inherited a disease-causing allele. This sort of test is available for members of families that have an autosomal dominant form of breast cancer and several genetic diseases for which there is not yet a cure, such as Huntington's disease. However, presymptomatic testing for incurable conditions raises several social and ethical questions.

Several hundred genetic diseases and disorders can now be diagnosed prenatally. The major purpose of these test is to provide information that is needed to make choices during pregnancies. There are a number of approaches to prenatal genetic tests:

• Preimplantation genetic diagnosis: Genetic testing can be combined with in-vitro fertilization to allow implantation of embryos that are free of a specific genetic defect. This technique allows people who carry a genetic defect to avoid producing a child with the disorder. The procedure begins with the production of several single-celled embryos through in-vitro fertilization. After several cell divisions, a single cell is removed and tested for the genetic abnormality. The disease-free embryos are selected and implanted in the woman’s uterus.
• Fetal cell sorting: Recent advances have made it possible to separate fetal cells from a maternal blood sample. These cells can be cultured to be used for chromosome analysis or as a source of fetal DNA for molecular testing.

• Chorionic villus sampling: A small piece of chrionic tissue is removed through suction by a rubber tube. This tissue is filled with dividing fetal cells, which can be used to prepare a karyotype, which is a picture of a complete set of metaphase chromosomes. Karyotypes can be studied for chromosomal abnormalities.
• Amniocentesis (see figure): A sample of amniotic fluid is taken from a pregnant women. This fluid contains fetal cells that can be used for genetic tests and the identification of rare genetic mutations.

• Ultrasonography: Some genetic conditions can be diagnosed by direct visualization of the fetus through ultrasound. High frequency sound waves are beamed into the uterus, where they bounce back on the dense tissue of the fetus.
• Maternal blood tests: Some genetic conditions can be discovered by performing a blood test on the mother. For instance, high levels of α-fetoprotein mean that the fetus has a neural-tube disorder.

Results of genetic tests are not always straight-forward. Therefore it is important that patients and their family ask questions about the test results before and after the test is performed. When interpreting the result, a person’s medical history, family history and the type of test should be taken into consideration.

A positive result means that a change in a certain gene or chromosome is found. This has implications for family members, since they share some genetic material. However, a positive result can’t be used to predict the severity of the disorder or the exact risk of developing it.

A negative test result means that no change has been found in the gene or chromosome that was considered. It is possible that the test missed a certain disease-causing gene, since many tests can’t detect all genetic alterations that can lead to a particular disorder, so it is recommended to do different tests.

http://www.bio.miami.edu/dana/pix/amniocentesis.jpg

• Genetics Home Reference: http://ghr.nlm.nih.gov/handbook/testing
• Pierce, B.A. (2007). Genetics: A Conceptual Approach. WH Freeman & Co