Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach

M. P. Johnson, E. Fitzpatrick, T. D. Dyer, J. B.M. Jowett, S. P. Brennecke, J. Blangero, E. K. Moses

    Research output: Contribution to journalArticle

    41 Scopus citations

    Abstract

    Pre-eclampsia/eclampsia (PE/E) is a common and serious disorder of human pregnancy that is associated with substantial maternal and perinatal morbidity and mortality. The suspected aetiology of PE/E is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. By assuming that the underlying liability towards PE/E susceptibility is inherently quantitative, any PE/E susceptibility gene would represent a quantitative trait locus (QTL). This assumption enables a more refined and powerful variance components procedure using a threshold model for our PE/E statistical analysis. Using this more efficient linkage approach, we have now re-analysed our previously completed Australian/New Zealand genome scan data to identify two novel PE/E susceptibility QTLs on chromosomes 5q and 13q. We have obtained strong evidence of linkage on 5q with a peak logarithm-of-odds (LOD) score of 3.12 between D5S644 and D5S433 [at ∼121 centimorgan (cM)] and strong evidence of linkage on 13q with a peak LOD score of 3.10 between D13S1265 and D13S173 (at ∼123 cM). Objective identification and prioritization of positional candidate genes using the quantitative bioinformatics program GeneSniffer revealed highly plausible PE/E candidate genes encoding aminopeptidase enzymes and a placental peptide hormone on the 5q QTL and two type IV collagens on the 13q QTL regions, respectively.

    Original languageEnglish (US)
    Pages (from-to)61-67
    Number of pages7
    JournalMolecular Human Reproduction
    Volume13
    Issue number1
    DOIs
    StatePublished - Jan 1 2007

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    Keywords

    • Genome scan
    • Linkage
    • Pre-eclampsia
    • Quantitative trait
    • Variance components

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Embryology
    • Molecular Biology
    • Genetics
    • Obstetrics and Gynecology
    • Developmental Biology
    • Cell Biology

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