Genetic code defects

The human body is made of about ten trillion cells (Nesse and Williams, 1994), (see also Human Ecology System, Section 5.5.3). Among all the actively dividing cells in the body, there are bound to be mistakes made in the genetic codes of some of them, and so there must be mechanisms to detect genetic mistakes and either (1) correct errors, or (2) destroy the cell with defective genes (apoptosis). If these cells are allowed to continue with defective genomes, they can become tumorous or cancerous. 

A genetic disease is the result of a defective enzyme caused by a mutation in its genetic code. For example, phenylketonuria (PKU) results when DNA cannot direct the synthesis of the enzyme phenylalanine hydroxylase, required for the conversion of phenylalanine to tyrosine. In an attempt to break down the phenylalanine, other enzymes in the cells convert it to phenylpyruvate. If phenylalanine and phenylpyruvate accumulate in the blood of an infant, it can lead to severe brain damage and mental retardation. If PKU is detected in a newborn baby, a diet is prescribed that eliminates all the foods that contain phenylalanine. Preventing the buildup of the phenylpyruvate ensures normal growth and development. 

Mitochondria are unique organelles in that they contain their own DNA (mtDNA), which, in addition to ribosomal RN A (rRNA) and transfer RN A (tRNA)-coding sequences, also encodes 13 polypeptides which are components of complexes I, III, IV, and V (Anderson et al., 1981). This fact has important implications for both the genetics and the etiology of the respiratory chain disorders. Since mtDNA is maternally-inherited, a defect of a respiratory complex due to a mtDNA deletion would be expected to show a pattern of maternal transmission. However the situation is complicated by the fact that the majority of the polypeptide subunits of complexes I, III, IV, and V, and all subunits of complex II, are encoded by nuclear DNA. A defect in a nuclear-coded subunit of one of the respiratory complexes would be expected to show classic Mendelian inheritance. A further complication exists in that it is now established that some respiratory chain disorders result from defects of communication between nuclear and mitochondrial genomes (Zeviani et al., 1989). Since many mitochondrial proteins are synthesized in the cytosol and require a sophisticated system of posttranslational processing for transport and assembly, it is apparent that a diversity of genetic errors is to be expected. 

Pereira, L., D Alessio, M., Ramirez, F., Lynch, J. R., Sykes, B., Pangilinan, T., and Bonadio, J. (1993). Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum. Mol. Genet. 2, 961-968. 

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