Multipoint Quantitative-Trait Linkage Analysis in
General Pedigrees
Laura Almasy and John Blangero
Department of Genetics, Southwest Foundation for Biomedical Research, San
Antonio
American Journal of Human Genetics,
62:1198-1211 (May 1998)
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 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.
Allele-sharing linkage analysis