The problem of ascertainment for linkage analysis.

摘要: It is generally believed that ascertainment corrections are unnecessary in linkage analysis, provided individuals selected for study solely on the basis of trait phenotype and not marker genotype. The theoretical rationale this standard analytic methods involve conditioning likelihoods all data, which may be viewed as an application assumption-free (AAF) method Ewens Shute. In paper, we show when observed pedigree structure depends relatives within a happen to have been probands (proband-dependent, or PD, sampling) data valid AAF will result asymptotically biased estimates genetic parameters (except under single ascertainment). Furthermore, holds even if recombination fraction R only parameter interest. Since lod score proportional likelihood conditional means obtained PD sampling yield R, so-called mod scores (i.e., maximized over both {theta} distribution)more » {theta}. problem appears intractable, sense it possible formulate correct structure. paper do investigate numerical magnitude bias, small many situations. On other hand, virtually sets collected sampling. Thus, existence bias rule rather than exception usual applications. 25 refs., 2 figs., 3 tabs.« less