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Medicine
and the New Genetics
Genomics and Its Impact on Science and Society: The Human Genome Project and Beyond
Gene Testing,
Pharmacogenomics, and Gene Therapy Gene
Testing
Currently, several hundred genetic tests are in clinical use, with many more under development, and their numbers and varieties are expected to increase rapidly over the next decade. Most current tests detect mutations associated with rare genetic disorders that follow Mendelian inheritance patterns. These include myotonic and Duchenne muscular dystrophies, cystic fibrosis, neurofibromatosis type 1, sickle cell anemia, and Huntington’s disease. Recently, tests have been developed to detect mutations for a handful of more complex conditions such as breast, ovarian, and colon cancers. Although they have limitations, these tests sometimes are used to make risk estimates in presymptomatic individuals with a family history of the disorder. One potential benefit to using these gene tests is that they could provide information to help physicians and patients manage the disease or condition more effectively. Regular colonoscopies for those having mutations associated with colon cancer, for instance, could prevent thousands of deaths each year. Some scientific limitations are that the tests may not detect every mutation associated with a particular condition (many are as yet undiscovered), and the ones they do detect may present different risks to different people and populations. Another important consideration in gene testing is the lack of effective treatments or preventive measures for many diseases and conditions now being diagnosed or predicted. Revealing information about the risk of future disease can have significant emotional and psychological effects as well. Moreover, the absence of privacy and legal protections can lead to discrimination in employment and insurance or other misuse of personal genetic information. Additionally, because genetic tests reveal information about individuals and their families, test results can affect family dynamics. Results also can pose risks for population groups if they lead to group stigmatization. Other issues related to gene tests include their effective introduction into clinical practice, the regulation of laboratory quality assurance, the availability of testing for rare diseases, and the education of healthcare providers and patients about correct interpretation and attendant risks. Families or individuals who have genetic disorders or are at risk for them often seek help from medical geneticists (an M.D. specialty) and genetic counselors (graduate-degree training). These professionals can diagnose and explain disorders, review available options for testing and treatment, and provide emotional support. (For more information, see Medicine and the New Genetics) Pharmacogenomics:
Moving Away from “One-Size-Fits-All” Therapeutics
More than 100,000 people die each year from adverse responses to medications that may be beneficial to others. Another 2.2 million experience serious reactions, while others fail to respond at all. DNA variants in genes involved in drug metabolism, particularly the cytochrome P450 multigene family, are the focus of much current research in this area. Enzymes encoded by these genes are responsible for metabolizing most drugs used today, including many for treating psychiatric, neurological, and cardiovascular diseases. Enzyme function affects patient responses to both the drug and the dose. Future advances will enable rapid testing to determine the patient’s genotype and guide treatment with the most effective drugs, in addition to drastically reducing adverse reactions. Gene Therapy,
Enhancement
More than 600 clinical gene-therapy trials involving about 3500 patients were identified worldwide in 2002.* The vast majority take place in the United States (81%), followed by Europe (16%). Although most trials focus on various types of cancer, studies also involve other multigenic and monogenic, infectious, and vascular diseases. Most current protocols are aimed at establishing the safety of gene-delivery procedures rather than effectiveness. Gene transfer still faces many scientific obstacles before it can become a practical approach for treating disease. According to the American Society of Human Genetics’ Statement on Gene Therapy, effective progress will be achieved only through continued rigorous research on the most fundamental mechanisms underlying gene delivery and gene expression in animals. *Source: Journal of Gene Medicine Web site (www.wiley.co.uk), accessed March 2003.
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DNA underlies almost every aspect of human health, both in function and dysfunction. Obtaining a detailed picture of how genes and other DNA sequences function together and interact with environmental factors ultimately will lead to the discovery of pathways involved in normal processes and in disease pathogenesis. Such knowledge will have a profound impact on the way disorders are diagnosed, treated, and prevented and will bring about revolutionary changes in clinical and public health practice. Some of these transformative developments are described below.
