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

39 Citations (Scopus)

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 2007
Externally publishedYes

Fingerprint

Eclampsia
Quantitative Trait Loci
Pre-Eclampsia
Chromosomes
Placental Hormones
Genes
Aminopeptidases
Collagen Type IV
Peptide Hormones
Perinatal Mortality
Computational Biology
New Zealand
Mothers
Genome
Morbidity
Pregnancy
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Genetics
  • Developmental Biology
  • Embryology
  • Cell Biology

Cite this

Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach. / Johnson, M. P.; Fitzpatrick, E.; Dyer, T. D.; Jowett, J. B M; Brennecke, S. P.; Blangero, J.; Moses, E. K.

In: Molecular Human Reproduction, Vol. 13, No. 1, 01.2007, p. 61-67.

Research output: Contribution to journalArticle

Johnson, M. P. ; Fitzpatrick, E. ; Dyer, T. D. ; Jowett, J. B M ; Brennecke, S. P. ; Blangero, J. ; Moses, E. K. / Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach. In: Molecular Human Reproduction. 2007 ; Vol. 13, No. 1. pp. 61-67.
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