Multipoint quantitative-trait linkage analysis in general pedigrees

L Almasy, J Blangero, 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 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.

References

    1. Hum Hered. 1971;21(6):523-42
    1. Genet Epidemiol. 1997;14(6):1065-70
    1. Ann Hum Genet. 1976 May;39(4):485-91
    1. Ann Hum Genet. 1982 Oct;46(Pt 4):373-83
    1. Ann Hum Genet. 1985 Oct;49(Pt 4):315-28
    1. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363-7
    1. Genet Epidemiol. 1988;5(6):471-2
    1. Am J Hum Genet. 1990 Nov;47(5):842-53
    1. Am J Hum Genet. 1990 Dec;47(6):957-67
    1. Am J Hum Genet. 1993 Jul;53(1):234-51
    1. Genet Epidemiol. 1993;10(4):217-24
    1. Am J Hum Genet. 1993 Dec;53(6):1306-19
    1. Hum Biol. 1993 Dec;65(6):941-66
    1. Am J Hum Genet. 1994 Mar;54(3):535-43
    1. Biometrics. 1994 Mar;50(1):109-17
    1. Am J Hum Genet. 1995 May;56(5):1224-33
    1. Am J Hum Genet. 1995 Aug;57(2):439-54
    1. Nat Genet. 1995 Nov;11(3):241-7
    1. Am J Hum Genet. 1996 Jun;58(6):1323-37
    1. Am J Hum Genet. 1996 Jun;58(6):1347-63
    1. Am J Hum Genet. 1996 Apr;58(4):867-80
    1. Ann Hum Genet. 1996 Mar;60(Pt 2):143-60
    1. Genome Res. 1996 Aug;6(8):724-34
    1. Behav Genet. 1996 Sep;26(5):527-32
    1. Nat Genet. 1997 Mar;15(3):273-6
    1. Am J Hum Genet. 1997 Sep;61(3):748-60
    1. Genet Epidemiol. 1997;14(6):719-35
    1. Genet Epidemiol. 1997;14(6):909-13
    1. Genet Epidemiol. 1997;14(6):953-8
    1. Genet Epidemiol. 1997;14(6):959-64
    1. Genet Epidemiol. 1997;14(6):987-92
    1. Genet Epidemiol. 1997;14(6):1011-6
    1. Genet Epidemiol. 1997;14(6):1053-8
    1. Behav Genet. 1972 Mar;2(1):3-19

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