Fine Mapping and SNP Analysis of Positional Candidates at the Preeclampsia Susceptibility Locus (PREG1) on Chromosome 2
| Autor: | D. W. Cooper, H Liu, Shaun P. Brennecke, Anthony J. Borg, Eric K. Moses, E. Fitzpatrick, S. Forrest, Harald H H Göring |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Genetics
Candidate gene Gene map Australia Iceland Chromosome Mapping Locus (genetics) Single-nucleotide polymorphism Quantitative trait locus Biology Polymorphism Single Nucleotide Pre-Eclampsia Pregnancy Genetic linkage Chromosomes Human Pair 2 Humans Microsatellite Female Disease Susceptibility Lod Score Genetics (clinical) Ecology Evolution Behavior and Systematics New Zealand SNP array |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1534-6617 |
| DOI: | 10.1353/hub.2005.0017 |
| Popis: | Genome scans in Icelandic, Australian and New Zealand, and Finnish families have localized putative susceptibility loci for preeclampsia/ eclampsia to chromosome 2. The locus mapped in the Australian and New Zealand study (designated PREG1) was thought to be the same locus as that identified in the Icelandic study. In both these studies, two distinct quantita- tive trait locus (QTL) regions were evident on chromosome 2. Here, we describe our fine mapping of the PREG1 locus and a genetic analysis of two positional candidate genes. Twenty-five additional microsatellite markers were genotyped within the 74-cM linkage region defined by the combined Icelandic and Australian and New Zealand genome scans. The overall posi- tion and shape of the localization evidence obtained using nonparametric multipoint analysis did not change from that seen previously in our 10-cM resolution genome scan; two peaks were displayed, one on chromosome 2p at marker D2S388 (107.46 cM) and the other on chromosome 2q at 151.5 cM at marker D2S2313. Using the robust two-point linkage analysis imple- mented in the Analyze program, all 25 markers gave positive LOD scores with significant evidence of linkage being seen at marker D2S2313 (151.5 cM), achieving a LOD score of 3.37 under a strict diagnostic model. Sugges- tive evidence of linkage was seen at marker D2S388 (107.46 cM) with a LOD score of 2.22 under the general diagnostic model. Two candidate genes beneath the peak on chromosome 2p were selected for further analysis using public single nucleotide polymorphisms (SNPs) within these genes. Maxi- mum LOD scores were obtained for an SNP in TACR1 (LOD3.5) and for an SNP in TCF7L1 (LOD3.33), both achieving genome-wide signifi- cance. However, no evidence of association was seen with any of the markers tested. These data strongly support the presence of a susceptibility gene on chromosome 2p11-12 and substantiate the possibility of a second locus on chromosome 2q23. 1 |
| Databáze: | OpenAIRE |
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