The positional cloning of genes underlying common complex diseases relies o
n the identification of linkage disequilibrium (LD) between genetic markers
and disease. We have examined 127 polymorphisms in three genomic regions i
n a sample of 575 chromosomes from unrelated individuals of British ancestr
y. To establish phase, 800 individuals were genotyped in 160 families. The
fine structure of LD was found to be highly irregular. Forty-five percent o
f the variation in disequilibrium measures could be explained by physical d
istance. Additional factors, such as allele frequency, type of polymorphism
, and genomic location, explained <5 % of the variation. Nevertheless, dise
quilibrium was occasionally detectable at 500 kb and was present for over o
ne-half of marker pairs separated by <50 kb. Although these findings are en
couraging for the prospects of a genomewide LD map, they suggest caution in
interpreting localization due to allelic association.