Disease genetic mutation

The development of analog-specific forms of nudear/steroid hormone receptors has prompted us to investigate many naturally occurring mutations found in nuclear receptors assodated with genetic disease. Mutations to... 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

In approaching the study of the molecular mechanisms of heredity, this chapter first discusses the structural and functional roles of the genetic material, DNA. This includes an analysis of its replication and susceptibility to mutation. The health-related aspects of the use of recombinant DNA techniques are considered, and examples of then-use in the analysis of several human genetic diseases are used to illustrate the biochemical side of genetics. 

Spiegel, A. M. Genetic basis of endocrine disease. Mutations in G proteins and G protein-coupled receptors in endocrine disease. /. Clin. Endocrinol. Metab. 81 2434—2442,1996. 

A successful tool in the early studies of metabolic pathways was blocking the pathway at some specific point. This could be done by the use of either mutants or inhibitors. Schekman et al have isolated a number of yeast mutants with blocks in their secretion pathway (Schekman, 1982). It is not yet known which proteins these mutations affect, but this is clearly a most promising approach for identifying those components involved in transport. In animal cells there are no cellular mutants with blocks in the intracellular transport of protein from the ER to the cell surface. There are, however, genetic diseases which affect the routing of lysosomal enzymes to the lysosomes (Neufeld et al, 1975 Sly and Fischer, 1982). For viruses it has been possible to isolate temperature-sensitive mutants in which a mutation in the viral glycoprotein arrests... 

Inherited mutations that result in defective DNA repair mechanisms are associated with a predisposition to the development of cancer. Some examples of such genetic diseases are ... 

It is now believed that a substantial proportion of the single nucleotide substitutions causing human genetic disease are due to misincorporation of bases during DNA replication. Which proofreading activity is critical in determining the accuracy of nuclear DNA replication and thus the base substitution mutation rate in human chromosomes ... 

Pleiotropy exists when a single disease-causing mutation affects multiple organ systems. Pleiotropy is a common feature of genetic diseases. 

In this chapter, we review some of the practical clinical applications of genetic research. Once a gene is identified, it becomes feasible to diagnose the associate genetic disease in at-risk individuals. In addition, gene therapy, the correction of mutations in cells, becomes a possibility. 

Individuals at risk for developing a genetic disease with a delayed age of onset may wish to learn whether they have inherited a disease-causing mutation (e.g., Huntington disease, femilial breast cancer, hemochromatosis, adenomatous polyposis coli). In some cases, presymptomatic diagnosis can be highly usefiil in preventing serious disease consequences before they occur (e.g., phlebotomy for hemochromatosis, early tumor detection for familial breast cancer). 

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