Mutation rates at two human Y-chromosomal microsatellite loci using small pool PCR techniques

Polymorphic Y-chromosomal short tandem repeats (Y-STRs) are being employed for phylogenetic and evolutionary studies as well as for forensic applicati ons, Precise knowledge of mutation types and rates is essential and has hit herto been obtained from computer simulation or small-sized father/son pair s, or derived from the more intensively studied autosomal STRs, respectivel y. To establish more accurate values we analysed about 18 000 DNA sequences isolated from sperm cells of three donors, representing highly validated o ffspring. Two loci were examined, i.e. DYS19 and DYS390. The methodology ap plied was small pool PCR with automated laser-induced fluorescence detectio n. The mutation rates for single repeat gains were determined as 0.18% [95% confidence interval (CI) 0.11-0.31%] for DYS390 and 0.21% (95% CI 0.13-0.3 3%) for DYS19, and two-repeat changes occurred in the order of 0.01%, Assum ing a similar rate for the loss of repeats, which could not be detected wit h our approach, we predict an overall mutation rate of similar to0.4% per g amete per generation for both Y tetranucleotide loci. Moreover, these resul ts support the stepwise mutation mechanism based on replication slippage. W e expect this approach to be useful for individual mutation risk determinat ion, as well as for studies concerning male history.