Bootstrapping in human genetic linkage

Linkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.