Optimal sibship selection for genotyping in quantitative trait locus linkage analysis

S. Purcell*, S. S. Cherny, J. K. Hewitt, P. C. Sham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 χ2 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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalHuman Heredity
Volume52
Issue number1
DOIs
StatePublished - May 2001
Externally publishedYes

Funding

FundersFunder number
National Eye InstituteR01EY012562

    Keywords

    • Linkage
    • Methodology
    • Quantitative trait loci
    • Selection
    • Sibs
    • Variance components

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