Estimating allele age

The age of an allele can be estimated both from genetic variation among dif ferent copies (intra-allelic variation) and from its frequency. Estimates b ased on intra-allelic variation follow from the exponential decay of Linkag e disequilibrium because of recombination and mutation. The confidence inte rval depends both on the uncertainty in recombination and mutation rates an d on randomness of the genealogy of chromosomes that carry the allele (the intra-allelic genealogy). Several approximate methods to account for variat ion in the intra-allelic genealogy have been derived. Allele frequency alon e also provides an estimate of age. Estimates based on frequency and on int ra-allelic variability can be combined to provide a more accurate estimate or can be contrasted to show that an allele has been subject to natural sel ection. These methods have been applied to numerous cases, including allele s associated with cystic fibrosis, idiopathic torsion dystonia, and resista nce to infection by HIV. We emphasize that estimates of allele age depend o n assumptions about demographic history and natural selection.