The factor IX gene as a model for analysis of human germline mutations: an update

Hum Mol Genet. 1996;5 Spec No:1505-14. doi: 10.1093/hmg/5.supplement_1.1505.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Age Factors
  • Base Sequence
  • Factor IX / genetics*
  • Founder Effect
  • Germ-Line Mutation*
  • Hemophilia B
  • Humans
  • Molecular Sequence Data
  • Mosaicism
  • Mutagenesis
  • Neoplasms / genetics
  • Nucleic Acid Conformation
  • Purines
  • Pyrimidines
  • Sex Ratio


  • Purines
  • Pyrimidines
  • Factor IX
  • pyrimidine
  • purine