Mutation as a cause of genetic disease

Mutational changes can be conveniently classified into two sorts: those that appear to involve single genes and are generally referred to as gene mutations, and those that involve chromosomal segments containing many genes, or even whole chromosomes, and are referred to as chromosomal mutations. Both of these kinds of mutation occur in germ-cell lineages and contribute substantially to inherited disease, or pre-disposition to disease, and both also occur in somatic cells and contribute to acquired disease. The mutation rates for inherited disease ascribed to mutation in a single gene differ for different genes and are age-dependent. Moreover, a single disease entity, such as haemophilia B, may be the result of any one of a number of different alterations within the gene responsible for the disease. The mutation rate for inherited chromosomal mutation is also age-dependent, particularly so in the case of mutations involving alterations in chromosome number. Studies in experimental animals demonstrate that exposure to physical or chemical mutagens results in increasing the incidence of inherited gene and chromosomal mutations. However, such increases have not been unequivocally demonstrated in human populations exposed to known mutagens. Studies on mutation in human lymphoid or epithelial somatic cells clearly demonstrate an increased frequency in cells taken from people exposed to ionizing radiations or chemical mutagens or in cells exposed in vitro. The consequences of such mutations will depend upon their nature and the origins and functions of the cells in which they occur. Of particular importance are mutations influencing cell growth and proliferation, and both gene and chromosomal mutations are implicated as causal factors in the development of human cancers.