title: The factor IX gene as a model for analysis of human germline mutations: an update.
abstract: The variation generated by germline mutation is essential for evolution, 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. Analysis of the factor IX gene in patients with hemophilia B has provided insights into the human germline mutational process. Herein, seven topics will be reviewed with emphasis on recent advances: (i) proposed mechanisms of deletions, inversions, and insertions; (ii) discordant sex ratios of mutation and associated age effects; (iii) somatic mosaicism; (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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Sommer
authors.forename: R P
authors.initials: RP
authors.lastname: Ketterling
mesh_terms: D000367:Age Factors; D001483:Base Sequence; D005164:Factor IX / Q000235:genetics*; D018703:Founder Effect; D018095:Germ-Line Mutation; D002836:Hemophilia B; D006801:Humans; D008969:Molecular Sequence Data; D009030:Mosaicism; D016296:Mutagenesis; D009369:Neoplasms / Q000235:genetics; D009690:Nucleic Acid Conformation; D011687:Purines; D011743:Pyrimidines; D012744:Sex Ratio
chemical_list: D011687:Purines; D011743:Pyrimidines; D005164:Factor IX; C030986:pyrimidine; C030985:purine