Age estimates of two common mutations causing factor XI deficiency: Recentgenetic drift is not necessary for elevated disease incidence among Ashkenazi Jews

The type II and type III mutations at the FXI locus, which cause coagulatio n factor XI deficiency, have high frequencies in Jewish populations. The ty pe III mutation is largely restricted to Ashkenazi Jews, but the type II mu tation is observed at high frequency in both Ashkenazi and Iraqi Jews, sugg esting the possibility that the mutation appeared before the separation of these communities. Here we report estimates of the ages of the type II and type III mutations, based on the observed distribution of allelic variants at a flanking microsatellite marker (D4S171). The results are consistent wi th a recent origin for the type III mutation but suggest that the type II m utation appeared >120 generations ago. This finding demonstrates that the h igh frequency of the type II mutation among Jews is independent of the demo graphic upheavals among Ashkenazi Jews in the 16th and 17th centuries.