Estimation of mutation rates from parentage exclusion data: applications to STR and VNTR loci

Nonpaternity is a common source of bias in estimating mutation rates when they are obtained from family data showing discordance of parental and children's genotypes. With the availability of hypervariable DNA markers, this source of bias can be largely eliminated. However, the proportion of cases where parentage exclusion is caused by presumed mutation(s) of parental alleles must be adjusted to obtain a valid mutation rate estimate. The present work derives the basis of this adjustment factor, called the proportional bias. This proportional bias depends upon the allele frequency distribution at the locus. The maximum and minimum bounds of the proportional bias depend on the number of alleles at the locus. Using data from Caucasian populations at tandem repeat loci commonly used for parentage testing and forensic identification purposes, we show that when mutation rates are estimated at these loci, the proportional bias is generally very close to the maximum possible value for the observed number of alleles (or binned fragment sizes) at each locus. The expected proportional bias decreases with increasing mutation rate at a locus. For the short tandem repeat loci, without bias correction, the direct count method can result in an underestimation of up to 60% of their true value. In contrast, for the minisatellite VNTR loci, even with crude measurements on allele sizes, we show that the absolute proportional bias is generally below the coefficient of variation of the direct estimates.