Multipoint quantitative-trait linkage analysis in general pedigrees

American Journal of Human Genetics
L Almasy, J Blangero

Abstract

Multipoint linkage analysis of quantitative-trait loci (QTLs) has previously been restricted to sibships and small pedigrees. In this article, we show how variance-component linkage methods can be used in pedigrees of arbitrary size and complexity, and we develop a general framework for multipoint identity-by-descent (IBD) probability calculations. We extend the sib-pair multipoint mapping approach of Fulker et al. to general relative pairs. This multipoint IBD method uses the proportion of alleles shared identical by descent at genotyped loci to estimate IBD sharing at arbitrary points along a chromosome for each relative pair. We have derived correlations in IBD sharing as a function of chromosomal distance for relative pairs in general pedigrees and provide a simple framework whereby these correlations can be easily obtained for any relative pair related by a single line of descent or by multiple independent lines of descent. Once calculated, the multipoint relative-pair IBDs can be utilized in variance-component linkage analysis, which considers the likelihood of the entire pedigree jointly. Examples are given that use simulated data, demonstrating both the accuracy of QTL localization and the increase in power provided by ...Continue Reading

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Citations

Feb 4, 2010·Archives of General Psychiatry·David C GlahnMichael A Escamilla
Sep 10, 2008·Archives of Internal Medicine·Evadnie RampersaudSoren Snitker
Jan 11, 2007·Archives of Ophthalmology·Priya DuggalJoan E Bailey-Wilson
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