Genetic causes

The special interest is the determination of Fe, as the acceleration of sclerosed process is connected with the accumulation of Fe in this organ. Copper is accumulated in tissues at the genetic caused diseases (Wilson Disease, Hemochromatosis). This is the alteration in elemental ratios (e.g., Cu/Zn), that is the marker of pathological process. 

We have since come to understand the underlying genetic causes for many of the previously known differences in enzymatic activity, most prominently with regard to the P450 enzyme family, and these have been the subject of recent reviews [1, 2]. 

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurones. In 15-25% of cases, the genetic cause of the disease is a mutation of the enzyme Cu+/Zn2+... 

Exhibits 2.2,2.3, and 2.4 provide examples of genetic causes of diseases, for example, cancer, sickle cell anemia, and cystic fibrosis. It should be noted that although some of these diseases are the result of mutations in a single gene (including Huntington s disease and Duchenne muscular dystrophy), most are due to the influence of multiple genes. 

Genetically caused polymorphisms are known for a number of enzymes, which metabolize chemicals, and are important for the interindividual variability to chemical exposures, especially if the polymorphic pathway represents the major route of elimination. Altered enzyme levels and activities may thus render some individuals more susceptible to exposure to chemicals than the general population. It could therefore be hypothesized that even a very low exposure to a chemical may be associated with various biological responses in such susceptible individuals as altered enzyme levels and activities may influence the individual s ability to detoxify a chemical or increase the conversion of a chemical to a toxic metabolite. 

Disturbances resulting from raised iron concentrations are less frequent. Known as hemochromatoses, these conditions can have genetic causes, or may be due to repeated administration of blood transfusions. As the body has practically no means of excreting iron, more and more stored iron is deposited in the organs over time in patients with untreated hemochromatosis, ultimately leading to severe disturbances of organ function. 

A. OTC is a metabolic enzyme required to break down ammonia. Total lack of this enzyme leads to death shortly after birth owing to a buildup of ammonia. The partial presence of OTC also leads to accumulation of ammonia, which can be controlled by drugs and dietary intake. The genetic cause of this disease, its morbidity, and the need for rapid production of OTC by adenoviral vectors may extend the life span of OTC-deficient newborns to allow for drug treatment and dietary manipulation. Jesse Gelsinger, the 18-year-old patient who was the first patient to die on a phase I gene therapy trial, had OTC deficiency. 

Katoh M, Cacheiro NLA, Cornett CV, Cain KT, Rutledge JC, Generoso WM (1989) Fetal anomalies produced subsequent to treatment of zygotes with ethylene oxide or ethyl methanesulfonate are not likely due to the unusual genetic causes. Mutat Res, 210 337-344. 

Diseases arising from genetic causes may be metabolic, cndocrinolugic, neurologic, or may develop as the result of mutation, organ implantation, and other factors. 

Neurological Disorders. Although there are other disorders that are suspect, but fully connected to genetic causes, (he principal connections already positively made an the muscular dystrophies. 

Alveoli represent the primary site for gas exchange within the lung, and thus their health is vital for survival. Alveolar conditions with a primary genetic cause, such as surfactant protein-B (SP-B) deficiency and SP-C deficiency, are prime candidates for a rAAV-gene therapy approach. Diseases in which alveoli are damaged secondary to other defects might also be treated with gene transfer. Such conditions include environmental toxin exposure, infectious diseases, and adult respiratory distress syndrome (ARDS) (Table 4.1) (Rolls et al., 1997, 1998, 2001 Cheers et al 1999 Ruan et al., 2002). 

Predictably, most of the mutations identified involve ion channels, the determinants of neuronal excitability (Mulley et al., 2003). Identification of the genetic causes of seizures has helped in understanding the mechanism of the disorder and in the discovery of new drugs that target these affected genes. 

Thus, while most interethnic differences in drug response are now known to have a genetic basis, it would be wrong to assume automatically that there must be a genetic cause. 

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