The research seeks to investigate the current methods of major gene localization through linkage studies and to develop new methods where appropriate. Particular attention will be paid to localizing disease loci. General methods for estimating the expected amount of information available in a particular pedigree structure will be developed, so that even for complex traits, it is possible to evaluate the utility of performing a linkage study. The classical methodology of LOD scores for two loci will be investigated to examine the power of the method, the estimates of recombination fraction obtained and the sample sizes required for accurate estimation of the recombination fraction. Various family structures will be examined to develop strategies for efficient mapping. These studies will be extended to linkage between three loci. In particular, the problem of determining gene order will be examined. Discussions of power for the three loci analysis will also consider the sample sizes required to infer interference or gene conversion. A simulation study will be undertaken to examine the genetic analysis of common disorders. In particular, the effect of not allowing the sporadic occurrence of the disorder on both pedigree and linkage analysis will be considered.
