Most pathological variants are the product of recent mutations, and this assumption underlies allele frequency-based methods. Negative selection is therefore taken into account, albeit indirectly, through allele frequency, for the evaluation of variants of unknown significance.

The analysis of graphs representing the genealogy of a variant may be viewed as an extension of this widely used method.

hierarchical genetic tree

Real genetic histories are complex graphs, with recurrent founder effects and bifurcations. The mosaic pattern of haplotypes observed around a single mutation results from several sequential founder events.

Calculating the age of a mutation is greatly simplified by assuming that present day haplotypes descended from a single common ancestor, with all branches of equal length.