Linkage disequilibrium (LD) mapping may be a powerful means for genome screening to identify susceptibility loci for common diseases. A new statistical approach for detection of LD around a disease gene is presented here. This method compares the distribution of haplotypes in affected individuals versus that expected for individuals descended from a common ancestor who carried a mutation of the disease gene. Simulations demonstrate that this method, which we term 'ancestral haplotype reconstruction' (AHR), should be powerful for genome screening of phenotypes characterized by a high degree of etiologic heterogeneity, even with currently available marker maps. AHR is best suited to application in isolated populations where affected individuals are relatively recently descended (<~25 generations) from a common disease mutation-bearing founder.,
American Journal of Human Genetics
Department of Clinical Genetics

Service, S., Lang, D. W. T., Freimer, N., & Sandkuijl, L. (1999). Linkage-disequilibrium mapping of disease genes by reconstruction of ancestral haplotypes in founder populations. American Journal of Human Genetics, 64(6), 1728–1738. doi:10.1086/302398