Optimal sibship selection for genotyping in quantitative trait locus linkage analysis

In this paper we present a novel method for selecting optimally informative sibships of any size for quantitative trait locus (QTL) linkage analysis. The method allocates a quantitative index of potential informativeness to e ach sibship on the basis of observed trait scores and an assumed true QTL m odel. Any sample of phenotypically screened sibships can therefore be easil y rank-ordered for selective genotyping. The quantitative index is the sibs hip's expected contribution to the non-centrality parameter. This expectati on represents the weighted sum of X-2 test statistics that would be obtaine d given the observed trait values over all possible sibship genotypic confi gurations; each configuration is weighted by the likelihood of it occurring given the assumed true genetic model. The properties of this procedure are explored in relation to the accuracy of the assumed true genetic model and sibship size. In comparison to previous methods of selecting phenotypicall y extreme sibships for genotyping, the proposed method is considerably more efficient and is robust with regard to the specification of the genetic mo del. Copyright (C) 2001 S. Karger AG, Basel.