We note that the idea that family members share long stretches of haplotype that are “identical-by-descent” underpins nearly all methods of linkage analysis. Furthermore, many early approaches for association analysis in pedigree data implicitly impute missing genotypes by considering the distribution of potential genotypes of each individual jointly with that of other individuals in the same pedigree (35, 45). The extension of this idea to the imputation of missing genotypes (as outlined above) was first described by Burdick and colleagues (12), who coined the term “in silico genotyping” to describe the idea that computational analyses could be used to replace laboratory based procedures in the determination of individual genotypes. To illustrate the potential of the approach, they re-analyzed the data of Cheung and colleagues (17). Cheung and colleagues sought to identify genetic variants associated with regulation of gene expression by examining RNA transcript levels and genotype data for individuals in the top two generations of the Centre d'Etude du Polymorphism Humain (CEPH) pedigrees (21). The CEPH pedigrees are three generation pedigrees with a structure similar to that of the cartoon
