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 each sibship on the basis of observed trait scores and an assumed true QTL model. Any sample of phenotypically screened sibships can therefore be easily rank-ordered for selective genotyping. The quantitative index is the sibship's expected contribution to the non-centrality parameter. This expectation represents the weighted sum of chi(2) test statistics that would be obtained given the observed trait values over all possible sibship genotypic configurations; 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 phenotypically extreme sibships for genotyping, the proposed method is considerably more efficient and is robust with regard to the specification of the genetic model.
Purcell
S
S
Social, Genetic and Developmental Research Centre, 111 Denmark Hill, Denmark Hill, London SE5 8AF, UK. s.purcell@iop.kcl.ac.uk
Cherny
S S
SS
Hewitt
J K
JK
Sham
P C
PC
D002874:Chromosome Mapping; D008040:Genetic Linkage; D005821:Genetic Techniques; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable