ESTIMATING THE AGE OF ALLELES BY USE OF INTRAALLELIC VARIABILITY

A method is presented for estimating the age of an allele by use of it s frequency and the extent of variation among different copies. The me thod uses the joint distribution of the number of copies in a populati on sample and the coalescence times of the intraallelic gene genealogy conditioned on the number of copies. The linear birth-death process i s used to approximate the dynamics of a rare allele in a finite popula tion. A maximum-likelihood estimate of the age of the allele is obtain ed by Monte Carlo integration over the coalescence times. The method i s applied to two alleles at the cystic fibrosis (CFTR) locus, Delta F5 08 and G542X, for which intraallelic variability at three intronic mic rosatellite loci has been examined. Our results indicate that G542X is somewhat older than Delta F508. Although absolute estimates depend on the mutation rates at the microsatellite loci, our results support th e hypothesis that Delta F508 arose <500 generations (approximate to 10 ,000 years) ago.