Most multipoint linkage programs assume linkage equilibrium among the markers being studied. This assumption is appropriate for the study of sparsely spaced markers with inter-marker distances exceeding a few centimorgans, because linkage equilibrium is expected over these intervals for almost all populations. However, with recent advances in high-throughput genotyping technology, much denser markers are available and linkage disequilibrium (LD) may exist among the markers. Applying linkage analyses that assume linkage equilibrium to dense markers may lead to bias. It is well known that misspecification of allele frequencies can cause inflation of LOD scores for both model-free [1] and model based [2,3] linkage approaches. However, estimating allele frequencies from the available data will generally correct this problem [4]. Rare exceptions such as unrecognized inbreeding at a high level or the presence of pronounced stratification might cause an excess of false-positive rates for linkage tests when only affected sib-pairs lacking parents are analyzed [5]. In the case of tightly linked loci, assuming linkage equilibrium for tightly linked markers causes incorrect inference of haplotype frequencies, which can lead to a bias similar to
