Recent human germ-line mutation: inferences from patients with hemophilia B

The gene encoding factor IX has a unique number of advantages for studying human germ-line mutations. Detailed analyses of the observed mutations of this gene, with special attention to the biases in the data, have provided information on mutational hotspots (including 'cryptic' dinucleotide repeats), mutation rates per base pair per generation, and the sex ratios of mutation. The evidence strongly suggests that the great majority of germ-line mutations result from endogenous processes, rather than exogenous mutagens. Perhaps nature does not permit environmental control of such an important process. Instead, the rate of germ-line mutation is placed under selective pressure, of which early-onset cancer may be an important mediator.