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Genes to diseases (G2D) computational method to identify asthma candidate genes

Tremblay Karine, Lemire Mathieu, Potvin Camille, Tremblay Alexandre, Hunninghake Gary M, Raby Benjamin A, Hudson Thomas J., Perez-Iratxeta Carolina, Andrade-Navarro Miguel A et Laprise Catherine. (2008). Genes to diseases (G2D) computational method to identify asthma candidate genes. PloS one, 3, (8), e2907.

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URL officielle: http://dx.doi.org/doi:10.1371/journal.pone.0002907

Résumé

Asthma is a complex trait for which different strategies have been used to identify its environmental and genetic predisposing factors. Here, we describe a novel methodological approach to select candidate genes for asthma genetic association studies. In this regard, the Genes to Diseases (G2D) computational tool has been used in combination with a genome-wide scan performed in a sub-sample of the Saguenay-Lac-St-Jean (SLSJ) asthmatic familial collection (n = 609) to identify candidate genes located in two suggestive loci shown to be linked with asthma (6q26) and atopy (10q26.3), and presenting differential parent-of-origin effects. This approach combined gene selection based on the G2D data mining analysis of the bibliographic and protein public databases, or according to the genes already known to be associated with the same or a similar phenotype. Ten genes (LPA, NOX3, SNX9, VIL2, VIP, ADAM8, DOCK1, FANK1, GPR123 and PTPRE) were selected for a subsequent association study performed in a large SLSJ sample (n = 1167) of individuals tested for asthma and atopy related phenotypes. Single nucleotide polymorphisms (n = 91) within the candidate genes were genotyped and analysed using a family-based association test. The results suggest a protective association to allergic asthma for PTPRE rs7081735 in the SLSJ sample (p = 0.000463; corrected p = 0.0478). This association has not been replicated in the Childhood Asthma Management Program (CAMP) cohort. Sequencing of the regions around rs7081735 revealed additional polymorphisms, but additional genotyping did not yield new associations. These results demonstrate that the G2D tool can be useful in the selection of candidate genes located in chromosomal regions linked to a complex trait.

Type de document:Article publié dans une revue avec comité d'évaluation
ISSN:1932-6203
Volume:3
Numéro:8
Pages:e2907
Version évaluée par les pairs:Oui
Date:2008
Sujets:Sciences naturelles et génie > Sciences naturelles > Biologie et autres sciences connexes
Sciences de la santé > Sciences médicales > Génétique
Département, module, service et unité de recherche:Départements et modules > Département des sciences fondamentales
Mots-clés:asthma, genetics, chromosome mapping, genome, genotyping, single nucleotide polymorphism, bioinformatics, genetic predisposition
Déposé le:26 janv. 2016 01:12
Dernière modification:05 déc. 2016 20:50
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Creative Commons LicenseSauf indication contraire, les documents archivés dans Constellation sont rendus disponibles selon les termes de la licence Creative Commons "Paternité, pas d'utilisation commerciale, pas de modification" 2.5 Canada.

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