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Mol. Hum. Reprod. Advance Access published online on November 4, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal095
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 7, 2006
Revised October 3, 2006
Accepted October 10, 2006

Article

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 1 *, E. Fitzpatrick 2, T.D. Dyer 1, J.B.M. Jowett 3, S.P. Brennecke 2, J. Blangero 1, and E.K. Moses 1

1 Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
2 Department of Perinatal Medicine, Royal Women’s Hospital, Carlton; Department of Obstetrics and Gynaecology, University of Melbourne, Carlton
3 International Diabetes Institute, Caulfield, Australia; ChemGenex Pharmaceuticals, Geelong, Melbourne, Australia

* To whom correspondence should be addressed.
M.P. Johnson, E-mail: mjohnson{at}darwin.sfbr.org


  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.

Keywords: genome scan/linkage/pre-eclampsia/quantitative trait/variance components.
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