Abstract for presentation at 11th International Congress of Human Genetics

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

  • Dr Matthew Johnson, Southwest Foundation for Biomedical Research, San Antonio, Texas., United States
  • Ms Elizabeth Fitzpatrick, Department of Perinatal Medicine, Royal Women’s Hospital & Department of Obstetrics & Gynaecology, University of Melbourne, Mel, Australia
  • Dr Thomas Dyer, Southwest Foundation for Biomedical Research, San Antonio, Texas., United States
  • Prof Shaun Brennecke, Department of Perinatal Medicine, Royal Women’s Hospital & Department of Obstetrics & Gynaecology, University of Melbourne, Mel, Australia
  • Dr John Blangero, Southwest Foundation for Biomedical Research, San Antonio, Texas., United States
  • Dr Eric Moses, Southwest Foundation for Biomedical Research, San Antonio, Texas., United States

    • 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. With very minimal discrimination amongst ethnic groups PE/E is characterized by the development in the latter half of pregnancy of new onset hypertension resolving post partum. In its most severe form significant proteinuria is evident. Utilizing a cohort of 34 Australian/New Zealand PE/E pedigrees our previous efforts identified a putative susceptibility locus on chromosome 2q by adopting a “classical” genetic linkage approach. We have now resolved the 2q linkage signal under the assumption that the underlying liability towards PE/E susceptibility is inherently quantitative. Under this assumption any PE/E susceptibility gene represents a quantitative trait locus (QTL), thus leading to a more refined (and novel) variance components procedure using a threshold model for our PE/E statistical analysis. We have now used this more “contemporary” genetic linkage approach to re-analyze our previously completed genome scan data to resolve two novel QTL regions on chromosomes 5q and 13q. Under a strict diagnostic PE model we have obtained strong evidence of linkage on 5q with a peak LOD of 3.12 between D5S424 (90.87cM) and D5S2115 (136.75cM) and strong evidence of linkage on 13q with a peak LOD of 3.10 between D13S158 (98.96cM) and D13S285 (123.78cM). To assist us with prioritization of positional candidate genes at these QTLs for further genetic interrogation we are applying an objective prioritization strategy that integrates quantitative bioinformatics, assessment of differential gene expression and SNP association analysis. Our top ranked positional candidate genes from this approach will be re-sequenced through our Australian/New Zealand PE/E pedigrees to identify all polymorphisms within these genes and use quantitative trait nucleotide analysis to identify the most likely functional variants.

    Conference Organiser - ICMS Pty Ltd