THE FACTOR-IX GENE AS A MODEL FOR ANALYSIS OF HUMAN GERMLINE MUTATIONS - AN UPDATE

The variation generated by germline mutation is essential for evolutio n, but individuals pay a steep price in the form of Mendelian disease and genetic predisposition to complex disease. Indeed, the health of a species is determined ultimately by the rate of germline mutation. An alysis of the factor IX gene in patients with hemophilia B has provide d insights into the human germline mutational process. Herein, seven t opics will be reviewed with emphasis on recent advances: (i) proposed mechanisms of deletions, inversions, and insertions; (ii) discordant s ex ratios of mutation and associated age effects; (iii) somatic mosaic ism; (iv) founder effects; (v) mutation rates; (vi) the factor IX gene as a germline mutagen test; and (vii) cancer as a possible mechanism for maintaining a constant rate of germline mutation.