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Multipoint quantitative-trait linkage analysis in general pedigrees (1998)
| Venue: | Am. J. Hum. Genet |
| Citations: | 566 - 60 self |
BibTeX
@ARTICLE{Almasy98multipointquantitative-trait,
author = {Laura Almasy and John Blangero},
title = {Multipoint quantitative-trait linkage analysis in general pedigrees},
journal = {Am. J. Hum. Genet},
year = {1998},
pages = {1198--1211}
}
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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 multi-point mapping approach of Fulker et al. to general rel-ative pairs. This multipoint IBD method uses the pro-portion 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 mul-tipoint relative-pair IBDs can be utilized in variance-component linkage analysis, which considers the likeli-hood of the entire pedigree jointly. Examples are given that use simulated data, demonstrating both the accu-racy of QTL localization and the increase in power pro-vided by multipoint analysis with 5-, 10-, and 20-cM marker maps. The general pedigree variance component and IBD estimation methods have been implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package.
Keyphrases
general pedigree multipoint quantitative-trait linkage analysis relative pair mul-tipoint relative-pair ibds general rel-ative pair multipoint identity-by-descent computer package ibd estimation method simple framework variance-component linkage method chromosomal distance general framework multipoint linkage analysis multipoint analysis general pedigree variance component genotyped locus 20-cm marker map multipoint ibd method small pedigree probability calculation arbitrary size sib-pair multi-point mapping approach sequential oligogenic linkage analysis routine multiple independent line entire pedigree qtl localization single line quantitative-trait locus variance-component linkage analysis arbitrary point
