Expected behavior of conditional linkage disequilibrium

Abstract

The ubiquitousness of RFLPs in the human genome has greatly helped the mapping of human disease genes, and it has been suggested that population measures of association between disease and marker loci could help with this mapping. For rare diseases, random samples are taken from within disease genotypes in order to obtain reasonable sample sizes, but this sampling strategy requires a modification of the usual measures of association. We present theoretical predictions for the mean and variance of such a modified measure, under the assumption that the disease gene is maintained at a constant low frequency in the population. The coefficient of variation of this modified measure is large enough that caution is needed in using the measure to locate disease genes, and, furthermore, the coefficient of variation cannot be made arbitrarily small by increasing sample size. The modified association measure is calculated for recently published data on cystic fibrosis.