Population genetic tools can facilitate successful conservation and management of wildlife populations. However, the ability of such approaches to inform wildlife management and conservation programs depends upon assumptions linking genetic patterns to ecological processes, one implicit assumption usually being that genetic parameters (e.g., population genetic differentiation) estimated using a set of loci accurately reflect underlying demographic and microevolutionary forces affecting the population(s) under study. This is an important assumption because it also implies that we have acknowledged that genetic parameters estimated by a set of target loci inherently are associated with a sampling variance. Specifically, a perception exists that heterozygote deficits caused by biological mechanisms (e.g., a Wahlund effect) and null alleles can be differentiated by the expectation that the former leads to a concordant pattern across all loci, whereas the latter leads to locus-specific effects. We use Monte-Carlo simulation to demonstrate that these expectations do not always hold under biologically realistic conditions. Our analyses indicate that the conservative approach of discarding loci deviating from Hardy-Weinberg equilibrium expectations could rob us of our most informative markers, weakening our ability to interpret biological phenomena. © 2012 The Wildlife Society.