Impact of linkage disequilibrium on multipoint linkage analysis

Abstract In this chapter we describe the impact that an inaccurate assumption of linkage equilibrium has upon linkage methods. Most multipoint linkage analysis programs assume linkage equilibrium among tightly linked markers. Violation of this assumption leads to biased evidence for linkage when analyzing affected sib‐pairs and an excess probability of falsely detecting evidence for linkage. Including the parents in the analysis or additional unaffected siblings reduces or eliminates this bias. Procedures for removing markers in strong linkage disequilibrium (LD) or for treating linked markers as sets of alleles at a single locus have been developed. Some parametric linkage methods can perform analysis incorporating haplotype frequencies among tightly linked markers, but these approaches are awkward to implement for dense multipoint mapping.