The Rates of G:C→T:A and G:C→C;G Transversions at CpG Dinucleotides in the Human Factor IX Gene

We have identified eight independent transversions at CpG in 290 consecutive families with hemophilia B. These eight transversions account for 16.3% of all independent transversions in our sample, yet the expected frequency of CpG transversions at random in the factor IX gene is only 2.6% (P<.01). The aggregate data suggest that the two types of CpG transversions (G:C→T:A and G:C→C:G) possess similar mutation rates (24.8 × 10^-10 and 20.6 × 10^-10, respectively), which are about fivefold greater than the comparable rates for transversions at non-CpG dinucleotides. The enhancement of transversions at CpG suggests that the model by which mutations occur at CpG may need to be reevaluated. The relationship, if any, between deamination of 5-methyl cytosine and enhancement of transversions at CpG remains to be defined.