The transmission/disequilibrium test and parental-genotype reconstruction: the reconstruction-combined transmission/ disequilibrium test.

Spielman and Ewens recently proposed a method for testing a marker for linkage with a disease, which combines data from families with and without information on parental genotypes. For some families without parental-genotype information, it may be possible to reconstruct missing parental genotypes from the genotypes of their offspring. The treatment of such a reconstructed family as if parental genotypes have been typed, however, can introduce bias. In the present study, a new method is presented that employs parental-genotype reconstruction and corrects for the biases resulting from reconstruction. The results of an application of this method to a real data set and of a simulation study suggest that this approach may increase the power to detect linkage.