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 that induced by misspecification of allele frequencies for multi-allelic markers. However, accurately estimating haplotype frequencies is more difficult than estimating allele frequencies because of phase uncertainty. Many currently available programs such as ALLEGRO and GENEHUNTER do not allow the user to specify haplotype frequencies, while programs that will allow the user to specify haplotypes, including LINKAGE and LIPPED are very unwieldy to use in this case.
