Allelic association between marker loci

Allelic association has proven useful to refine the location of major genes prior to positional cloning, but it is of uncertain value for genome scans in complex inheritance. We have extended kinship theory to give informatio n content for linkage and allelic association. Application to pairs of clos ely linked markers as a surrogate for marker x oligogene pairs indicates th at association is largely determined by regional founders, with little effe ct of subsequent demography. Sub-Saharan Africa has the least allelic assoc iation, consistent with settlement of other regions by small numbers of fou nders. Recent speculation about substantial advantages of isolates over lar ge populations, of constant size over expansion, and of F-1 hybrids over in crosses is not supported by theory or data. On the contrary, fewer affected cases, less opportunity for replication, and more stochastic variation ten d to make isolates less informative for allelic association, as they are fo r linkage.