The incorporation of prior genomic information does not necessarily improve the performance of Bayesian linkage methods: an example involving sex-specific recombination and the two-point PPL

OBJECTIVE: We continue statistical development of the posterior probability of linkage (PPL). We present a two-point PPL allowing for unequal male and female recombination fractions, thetaM and thetaF, and consider alternative priors on thetaM, thetaF. METHODS: We compare the sex-averaged PPL (PPLSA), assuming thetaM = thetaF, to the sex-specific PPL (PPLSS) in (thetaM, thetaF), in a series of simulations; we also compute the PPLSS using alternative priors on (thetaM, thetaF). RESULTS: The PPLSS based on a prior that ignores prior genomic information on sex specific recombination rates performs essentially identically to the PPLSA, even in the presence of large thetaM, thetaF differences. Moreover, adaptively skewing the prior, to incorporate (correct) genomic information on thetaM, thetaF differences, actually worsens performance of the PPLSS. We demonstrate that this has little to do with the PPLSS per se, but is rather due to extremely high levels of variability in the location of the maximum likelihood estimates of (thetaM, thetaF) in realistic data sets. CONCLUSIONS: Incorporating (correct) prior genomic information is not always helpful. We recommend that the PPLSA be used as the standard form of the PPL regardless of the sex-specific recombination rates in the region of the marker in question.