Conditional tests for localizing trait genes.

BACKGROUND/AIMS With pedigree data, genetic linkage can be detected using inheritance vector tests, which explore the discrepancy between the posterior distribution of the inheritance vectors given observed trait values and the prior distribution of the inheritance vectors. In this paper, we propose conditional inheritance vector tests for linkage localization. These conditional tests can also be used to detect additional linkage signals in the presence of previously detected causal genes. METHODS For linkage localization, we propose to perform inheritance vector tests conditioning on the inheritance vectors at two positions bounding a test region. We can detect additional linkage signals by conducting a further conditional test in a region with no previously detected genes. We use randomized p values to extend the marginal and conditional tests when the inheritance vectors cannot be completely determined from genetic marker data. RESULTS We conduct simulation studies to compare and contrast the marginal and the conditional tests and to demonstrate that randomized p values can capture both the significance and the uncertainty in the test results. CONCLUSIONS The simulation results demonstrate that the proposed conditional tests provide useful localization information, and with informative marker data, the uncertainty in randomized marginal and conditional test results is small.