A comparison of linkage disequilibrium measures for fine-scale mapping
- Yale Univ. School of Medicine, New Haven, CT (United States)
Linkage mapping generally localizes disease genes to 1-to 2-cM regions of chromosome. In theory, further refinement of location can be achieved by population-based studies of linkage diequilibrium between disease locus alleles at adjacent markers. One approach to localization, dubbed simple disequilibrium mapping, is to determine the relative location of the disease locus by plotting disequilibrium values against marker locations. We investigate the simple mapping properties of five disequilibrium measures, the correlation coefficient {Delta}, Lewontin`s D`, the robust formulation of the population attribute risk {delta}, Yule`s Q, and Kaplan and Weir`s proportional difference d under the assumption of initial complete disequilibrium between disease and marker loci. The studies indicate that {delta} is a superior measure for fine mapping because it is directly related to the recombination fraction between the disease and the marker sampled at a rate higher than their population frequencies, as in a case-control study. D` yields results of comparable to those of {delta} in many realistic settings. Of the remaining three measures, Q,{Delta}, and d, Q yields the best results. From simulations of short-term evolution, all measures show some sensitivity to marker allele frequencies; however, as predicted by analytic results, Q, {Delta}, and d exhibit the greatest sensitivity to variation in marker allele frequencies across loci. 56 refs., 1 fig., 6 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 258254
- Journal Information:
- Genomics, Vol. 29, Issue 2; Other Information: PBD: 20 Sep 1995
- Country of Publication:
- United States
- Language:
- English
Similar Records
Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE)
Mapping by admixture linkage disequilibrium in human populations: Limits and guidelines