The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene

Hum Genet. 1993 Jun;91(5):496-503. doi: 10.1007/BF00217779.


Mutations at CpG dinucleotides were delineated in the factor IX gene of 38 hemophilia B patients. When transitions at CpG were considered with those previously reported by us and those compiled in the factor IX mutation database, the following patterns emerged. Many CpG sites were mutated with high frequency, while two CpG sites were infrequently mutated (R29-->Q and R116-->TGA). Of the 6 possible nonsense mutations and the 14 missense mutations that would produce a nonconservative change at conserved amino acids, all have been observed to cause hemophilia B except A-10-->T and R338-->Q. By contrast, none of the 6 missense changes at nonconserved amino acids have been observed to cause hemophilia B. At those CpG sites that are frequently mutated, the rate of transitions is estimated to be 20-fold higher than transitions at non-CpG sites. Point mutations in close proximity to CpG dinucleotides did not seem elevated.

Publication types

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

MeSH terms

  • DNA Mutational Analysis
  • Dinucleoside Phosphates / genetics*
  • Factor IX / genetics*
  • Gene Expression
  • Haplotypes
  • Hemophilia B / genetics*
  • Humans
  • Male
  • Mutation*
  • Severity of Illness Index


  • Dinucleoside Phosphates
  • cytidylyl-3'-5'-guanosine
  • Factor IX