Clinical molecular biology: Principles

Abstract

The information that gives life to humans and all organisms, viruses, and plants is kept in two types of nucleic acid, DNA and RNA. DNA and RNA store, express, transmit, and regulate this genetic information in unique, predetermined sequences of only four nucleic acid bases. Such DNA is located in the cell nucleus and mitochondria in chromosomes and mitochondrial DNA (mtDNA), which contain hereditary material encoding proteins and regulatory molecules. Surprisingly, much nuclear DNA consists of short repeated syllables 1 to 20 bases in length. DNA could thus be classified according to the repeat number and the size of repeating sequences. DNA replicates according to the semiconservative role in which one of the two sequence strands is completely new. The new and old strands distribute the replicated DNA equally into two daughter cells. DNA mutation, a permanent alteration in the genetic material sequence, is one of the major mechanisms of pathogenesis. Many environmental and internal factors cause DNA mutation, which can often, however, be fixed by DNA repair mechanisms. Generalized gene instability occurs, therefore, when DNA repair genes are impaired. Genes are DNA sequences that encode heritable biologic characteristics. Housekeeping genes are genes required for maintenance of basic cellular functions; facultative genes are transcribed only when needed for the cell to respond to its environment. Inducible genes are expressed either in response to environmental signals or in dependence on the stage of the cell cycle. Pseudogenes are multiple copy genes characterized by homology to a known gene and yet nonfunctional due to mutation or obsolescence. Gene functions are regulated by signal molecules produced by other genes. Tumor suppressor genes and oncogenes play a significant role in carcinogenesis when altered, either structurally or functionally. Genes perform their function following the central dogma, that genetic information is transferred through DNA to RNA and then to protein. MtDNA, a double-stranded circular chromosome located in the mitochondria, is usually present as 2-10 copies per mitochondrion. It is associated with mitochondrial disease when mutated or dysregulated.