Some effects of selection strategies on linkage analysis

A study was designed to address the relative merits of different sampling strategies for detecting linkage. Genotypes of pedigree members were generated by the use of a single genetic model, and the pedigrees were subdivided into dominant-appearing, recessive-appearing, and "interesting" subsets. An investigator blind to how the data had been generated applied two different selection rules to determine which individuals in each pedigree would be "typed" for linkage analysis. Linkage analyses were then conducted on these pedigree subsets, as well as on the combined data, by the use of three autosomal dominant models, three autosomal recessive models, and the generating (i.e., "true") model. Results suggest (1) that linkage is likely to be detected even in the absence of knowledge of the mode of transmission, if a range of models can be examined; (2) that false evidence for heterogeneity will not necessarily result when pedigrees are selected according to apparent mode of transmission for analysis; (3) that recessive-appearing pedigrees (i.e., those with multiplex sibships) may be particularly useful for detecting linkage; and (4) that including information on unaffected second-degree relatives adds little to linkage studies of affected individuals and their first-degree relatives.