Genetic linkage studies for the identification of cancer-related genes.

The most commonly used method for genetic mapping of disease causing loci is the lod-score method, based on maximum likelihood estimation of the recombination fraction. This method is the most powerful one when the mode of inheritance of the disease is known, but is often used also for genetic mapping of complex traits, although in these cases alternative non parametric procedures are often preferable. In those families where cancer segregates as a Mendelian disease, mapping of the corresponding gene can be carried out as for any other genetic disorder. Modelling of the analysis should also consider the possible occurrence of reduced or age dependent penetrance, phenocopies, and genetic heterogeneity. The application of this method has already led to the identification of the genetic location and eventually to the cloning of several cancer-related genes, including FAP, BRCA1, NF1, and more recently AT. Understanding the molecular mechanisms leading to the disease in the Mendelian forms of cancer may prove helpful in unraveling the basis of the other more common forms of cancer.