THE RATES OF C-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 X 10(-10) and 20.6 x 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.