Genetics is a branch of biology concerned with the components and function of biologic inheritance. Genetic testing investigates the presence, absence, or activity of genes through direct and indirect means and by chemical analysis, microscopic methods, submicroscopic techniques, and molecular biology studies. Cytogenetics is the part of genetics concerned with the structure and functions of cells, especially chromosomes. Genetic tests are done to identify inborn errors of metabolism (IEMs), to determine sex when ambiguous genitalia are present, and to detect chromosome aberrations such as Down syndrome. As genetics moves toward genomics, the thrust expands from considering the effects of single genes to the interactions and subsequent functions of genes within the genome.
Insight into causes of developmental problems, birth defects, and heritable disorders often involves genetic studies. Basic technology counts the chromosomes in a person’s cells or measures the amount of specific proteins and enzymes. At the other end of the spectrum, cellular DNA can be assayed with molecular probes designed to identify a unique genetic sequence. Genetic testing is a rapidly evolving field that has shown expanding possibilities, an ever-increasing number of tests, and a unique set of limitations and dilemmas. The challenge includes the interactions of maternal, paternal, and fetal genomes.
Many disease states reflect hereditary components even though general clinical studies usually focus on the disorder itself rather than on its genetic components. This section addresses circumstances that may require biochemical analysis (enzymes, organic acids, amino acids) and DNA tests or cytogenetic (chromosome) studies for proper diagnosis and management.
Testing may be done before birth, neonatally, during childhood or adult life, or postmortem.
Biochemical analysis and tests to detect carrier status of IEMs are done, primarily through detection of abnormal accumulation in body fluids and tissue. Advances in the study of molecular genetics have been affected by the completion of the Human Genome Project in 2003. Tests in this category include diagnosis of neoplastic disease (e.g., Philadelphia chromosome in chronic myelocytic leukemia and N-MYC gene in neuroblastoma) and inherited disorders (e.g., cystic fibrosis, spinal cerebellar ataxia). Along with genetic testing, a thorough clinical assessment and family history are integral components when diagnosing genetic disorders.
In 2004, the FDA approved the DNA technology of Roche Diagnostics (Indianapolis, IN) to aid healthcare providers in assessing treatment strategy and dose. The Roche AmpliChip® CYP450 Test is used to identify a patient’s CYP2D6 and CYP2C19 (cytochrome P450 isoenzymes) genotype from genomic DNA. These isoenzymes are involved in the metabolism of several antidepressants, antipsychotic agents, and antiarrhythmic agents. Identification of the patient’s genotype can be predictive of drug metabolism, thereby improving outcome by reducing adverse drug reactions and improving efficacy.
When considering whether or not a patient is a candidate for genetic testing, the following should be taken into consideration: a comprehensive history of the patient’s health and lifestyle, family history (tracing back two or three generations if possible), reasons for requesting testing, and available support system. A support system is crucial should the results of testing be positive.
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