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| Practical Applications of Genomics |
Genome sequence data now provide tools for the development of practical uses for genetic information. DNA is an invaluable tool in forensics because - aside from identical twins - every individual has a uniquely different DNA sequence. Repeated DNA sequences in the human genome are sufficiently variable among individuals that they can be used in human identity testing. The FBI uses a set of thirteen short tandem repeat (STR) DNA sequences for the Combined DNA Index System (CODIS) database, which contains the DNA fingerprint or profile of convicted criminals. Investigators of a crime scene can use this information in an attempt to match the DNA profile of an unknown sample to a convicted criminal. DNA fingerprinting can also identify victims of crime or catastrophes, as well as many family relationships, such as paternity. While we think of forensics in terms of identifying people, it can also be used to match donors and recipients for organ transplants, identify species, establish pedigree, or even detect organisms in water or food. (See the Evolution and Phylogenetics unit.)
An unusual application of DNA fingerprinting technology is a project of Mary-Claire King's at the University of Washington. (See the Cell Biology and Cancer unit.) Although her research is primarily concerned with the identification of genetic markers for breast cancer, she also has a project to help the "Abuelas," or grandmothers, in Argentina. In Buenos Aires in the 1970s and 1980s, children of activists "disappeared" during the military dictatorship. The children were placed in orphanages or illegally adopted when their parents were killed. Now King is using mitochondrial DNA, which is inherited only maternally, to reunite the children with their grandmothers.
The basis of many diseases is the alteration of one or more genes. Testing for such diseases requires the examination of DNA from an individual for some change that is known to be associated with the disease. Sometimes the change is easy to detect, such as a large addition or deletion of DNA, or even a whole chromosome. Many changes are very small, such as those caused by SNPs. Other changes can affect the regulation of a gene and result in too much or too little of the gene product. In most cases if a person inherits only one mutant copy of a gene from a parent, then the normal copy is dominant and the person does not have the disease; however, that person is a carrier and can pass the disease on to offspring. If two carriers produce a child and each passes the mutant allele to the child (a one-in-four probability), that individual will have the disease.
Several different mutations in a gene often lead to a particular disease. Many diseases result from complex interactions of multiple gene mutations, with the added effect of environmental factors. Heart disease, type-2 diabetes and asthma are examples of such diseases. (See the Human Evolution unit.) Many diseases do not show simple patterns of inheritance. For example, the BRCA1 mutation is a dominant mutant allele that leads to an increased risk for breast and ovarian cancer. (See the Cell Biology and Cancer unit.) Although not everyone with the mutation develops the disease, the risk is much higher than for individuals without the mutation.
Newborns commonly receive genetic testing. The tests detect genetic defects that can be treated to prevent death or disease in the future. Apparently normal adults may also be tested to determine whether they are carriers of alleles for cystic fibrosis, Tay-Sachs disease (a fatal disease resulting from the improper metabolism of fat), or sickle cell anemia. This can help them determine their risk of transmitting the disease to children. These tests as well as others (such as for Down's syndrome) are also available for prenatal diagnosis of diseases. As new genes are discovered that are associated with disease, they can be used for the early detection or diagnosis of diseases such as familial adenomatous polyposis (associated with colon cancer) or p53 tumor-suppressor gene (associated with aggressive cancers). The ultimate value of gene testing will come with the ability to predict more diseases, especially if such knowledge can lead to the disease's prevention.
Gene therapy is a more ambitious endeavor: its goal is to treat or cure a disease by providing a normal copy of the individual's mutated gene. (See the Genetically Modified Organisms unit.) The first step in gene therapy is the introduction of the new gene into the cells of the individual. This must be done using a vector (a gene carrier molecule), which can be engineered in a test tube to contain the gene of interest. Viruses are the most common vectors because they are naturally able to invade the human host cells. These viral vectors are modified so that they can no longer cause a viral disease.
Gene therapy using viral vectors does have a few drawbacks. Patients often experience negative side effects and expression of the desired gene introduced by viral vectors is not always sufficiently effective. To counter these limitations, researchers are developing new methods for the introduction of genes. One novel idea is the development of a new artificial human chromosome that could carry large amounts of new genetic information. This artificial chromosome would eliminate the need for recombination of the introduced genes into an existing chromosome. Gene therapy is the long-term goal for the treatment of genetic diseases for which there is currently no treatment or cure.