The weighted-sum method is designed for resequencing data, since this technology allows rare mutations to be observed directly. The use of inferred haplotypes from tag SNP studies is a current approach to evaluation of unobserved variants, but this approach fails when the unobserved variants are rare; the tag SNP approach is hence not suited for the scenario of multiple rare disease-mutations [2]. Alternatively, familial linkage studies are a strategy to identify mutations underlying genetically heterogeneous diseases, but when the marginal effect of each mutation is low, it may be difficult to obtain a sufficient number of affected individuals to detect a disease association [40],[41].
