Prospects for whole-genome linkage disequilibrium mapping of common disease
genes
L Kruglyak
Fred Hutchinson Cancer Research Center,
1100 Fairview Avenue North, Seattle, Washington
98109, USA. leonid@fhcrc.org
Recently, attention has focused on the use of whole-genome linkage disequilibrium
(LD) studies to map common disease genes. Such studies would employ a dense
map of single nucleotide polymorphisms (SNPs) to detect association between
a marker and disease. Construction of SNP maps is currently underway. An essential
issue yet to be settled is the required marker density of such maps. Here,
I use population simulations to estimate the extent of LD surrounding common
gene variants in the general human population as well as in isolated populations.
Two main conclusions emerge from these investigations. First, a useful level
of LD is unlikely to extend beyond an average distance of roughly 3 kb in
the general population, which implies that approximately 500,000 SNPs will
be required for whole-genome studies. Second, the extent of LD is similar
in isolated populations unless the founding bottleneck is very narrow or the
frequency of the variant is low (<5%).
