Declaration ‘diseases Genetics has expanded the knowledge of many diseases and has often meant that they were reclassified. For example, the classification of many spinocerebellar ataxia is based no longer on the clinical criteria but on genetic criteria (Hereditary ataxias). The “Online Mendelian Inheritance in Man” (OMIMDatenbank) is a searchable catalog of human genes and genetic disorders. Diagnostic genetic tests for diagnosis of many diseases (eg. B. Turner’s syndrome, Klinefelter’s syndrome, hemochromatosis) is used. The diagnosis of genetic disease often means that family members of the person concerned on the genetic defect or carrier status can be screened. A directory of genetic testing is available worldwide by Gene tests. Reviews of many genetic diseases with diagnostic strategies and recommendations for risk advice are available from GeneReviews. Genetic screening If an increased risk for a particular genetic disorder in a population may be appropriate genetic checkups and screenings. The usual criteria for genetic screening are: genetic inheritance patterns are known. There is an effective therapy. Screening tests are sufficiently valid, reliable, sensitive and specific, non-invasive and safe. To justify the cost of screening, the prevalence in a defined group must be correspondingly high. One goal of prenatal genetic testing (Prenatal genetic counseling and evaluation) is to identify asymptomatic parental heterozygotes that carry a gene for a recessive disease. For example, Ashkenazi Jews are screened for Tay-Sachs disease, and dark-skinned people on sickle cell anemia, as well as several ethnic groups on thalassemia (see Table: Genetic screening for all ethnic groups). If the partner is a heterozygous also heterozygous, there is a danger that the couple gets a sick child. If the risk is high enough, a prenatal diagnosis for the application (such. As with amniocentesis, chorionic villus sampling, sampling from umbilical cord blood, maternal blood sampling or ultrasound) may occur. In some cases can be dealt with genetic disorders that were diagnosed prenatally, to prevent complications. For example, a special diet or replacement therapy can be used to mitigate the effects of phenylketonuria, galactosemia and hypothyroidism or prevent. Corticosteroids may come even before birth used to mitigate the severity of a hereditary virilizing Nebennierenrindenhypoplasie. A screening can be useful for people with a family dominantly inherited disease that manifests itself later in life, such as Huntington’s disease or cancer with abnormalities associated BRCA1 and BRCA2 gene. This is illegal in Germany to the Genetic Engineering Law. A screening reveals the risk of developing a disease for the person who can take appropriate precautions then such. B. frequent screening or preventive therapy. Screening can also be displayed when a family member with a genetic disorder is diagnosed. A person who is identified as a carrier can make informed decisions about family planning. Treatment Understanding the genetic and molecular basis of diseases, can help in the treatment. For example, a special diet to avoid substances that are toxic to patients with certain genetic defects such as phenylketonuria or homocystinuria, be useful. Vitamins or other drugs can reduce toxic levels of a substance by improving their biodegradability; Folic acid causes such. B. a decrease in the concentration of homocysteine ??in humans with 5,10-methylene tetrahydro folate reductase polymorphism. The therapy can also consist in compensating defects (replacement) or active metabolic pathways to inhibit. Pharmacogenetics Pharmacogenetics is the science of how genetic characteristics influence the response to drugs. One aspect of pharmacogenetics how the genes affect the pharmacokinetics. Genetic characteristics of a person can help to assess the response to certain treatments. For example, the metabolism of warfarin (R) in part by variations in the genes for the enzyme CYP2C9 and for the vitamin K epoxide reductase complex is determined 1 protein. Genetic variations (z. B. in the production of UDP [uridine diphosphate] -glucoronosyltransferase 1A1) can help predict is whether the cancer drug irinotecan will have very dangerous side effects. Another aspect of pharmacogenetics is the pharmacodynamics, so how drugs with cell receptors interact (overview on pharmacodynamics). Genetic and thus receptor properties of diseased tissue can be helpful in more goals in the development of drugs (eg. As cytostatics) to identify. For example, trastuzumab can affect with amplification of the HER2 / neu gene target specific cancer cell receptors in metastatic breast cancer. Detection of the Philadelphia chromosome in patients with chronic myelogenous leukemia (CML), the treatment with chemotherapy safer leiten.Gentherapie Gene therapy can generally be considered any treatment that alters the gene function. However, it is often regarded as gene therapy especially introducing normal genes into the cells of a person when these normal genes due to a specific genetic disease are lacking. The normal genes can be produced by PCR, and this for normal DNA, which was donated by another person. Since most genetic diseases are recessive, usually a dominant normal gene is introduced. Currently, these insertional gene therapy is most likely used in the prevention or healing of Einzelgendefekten such. As in cystic fibrosis. One method to transfer DNA into host cells, viral transfection. The normal DNA is introduced into a virus, which is then introduced into the host cells, causing a transfer of the DNA takes place in the nucleus. Some major concerns in this viral method are the physical reaction to the virus and the rapid loss of the new normal DNA, as well as damage to the virus through the development of antibodies to the transfected protein that the immune system recognizes as foreign. Another way to transfer DNA is the use of liposomes, which are absorbed by the host cells and thereby transfer the DNA into the nucleus. Among the possible problems with the liposome insertion methods the inability to take up the liposomes into the cells, the rapid destruction of the new normal DNA, and a lack of integration of the DNA counts. In the antisense technology, rather than by introducing normal genes that gene expression can be altered; z. B. drugs can be combined with specific Genanteilen that prevent gene expression or mitigate. Antisense technology is currently being explored for cancer therapy, but is still very experimental. However, they seem to be more promising than the Geninsertionstherapie because the success rate may be higher and complications lower. Another approach of gene therapy to modify the expression chemical means (for. example, by modifying the DNA methylation). Such methods have been studied experimentally in the treatment of cancer. The chemical modification may also have implications for genomic imprinting, although this effect has not yet been fully explained. Gene therapy is also being investigated experimentally in transplant surgery. The change in the genes of transplanted organs, to make them more compatible, may reduce the rejection of the new organ (and makes the use of immunosuppressive drugs unnecessary). However, this method rarely works. Key points A genetic screening is justified only if the prevalence of the disease is high enough, treatment is possible, and tests are accurate enough.