LINKAGE DISEQUILIBRIUM MEASURES FOR FINE-SCALE MAPPING - A COMPARISON

We investigate properties of simple linkage disequilibrium mapping for five measures in the presence of mutation at the marker and/or the di sease locus and of initial incomplete linkage disequilibrium. In contr ast to the stimulation approach that Devlin and Risch used, we calcula te the expected values of various linkage disequilibrium measures unde r different assumptions based on a framework for linkage disequilibriu m mapping. These expected values clearly demonstrate the expected perf ormance of these measures. We fmd that the impact of marker mutation o n their performance depends on the magnitude of the mutation relative to the proximity of the marker (i.e. recombination fraction between th e marker and the disease locus). In the presence of recurrent mutation at the marker and/or disease locus, the performance of all measures, including the robust one, depends on the marker allele frequency. The initial incomplete linkage disequilibrium could render all measures us eless. These expected values also show clearly why in Devlin and Risch 's simulation some measures performed very badly under certain circums tances.