title: Detection and characterization of DNA variants in the promoter regions of hundreds of human disease candidate genes.
abstract: Understanding genetic variation might reveal the cause of individual susceptibility to a variety of complex diseases such as asthma, diabetes, and cancer. Current efforts to identify functional DNA variants have essentially been oriented toward single nucleotide polymorphisms (SNPs) found in coding regions of candidate genes since they have direct impact on the structure and function of the affected proteins. Abnormal expression of finely regulated genes could also lead to disequilibria in different metabolic pathways and/or biological processes. Thus investigation of SNPs in the promoter regions (pSNPs) of genes should improve our knowledge of the etiology of complex diseases. Unfortunately, little is known about the nature and the prevalence of pSNPs. We have analyzed 197 genes targeting the promoter region, arbitrarily defined as a 2-kb genomic segment upstream of the transcription initiation site, by screening by dHPLC for the presence of SNPs in a worldwide panel of 40 individuals. As a result 1838 pSNPs were detected, 75% of which modify (by either gain or loss) putative binding sites of known transcription factors. We also examined the distribution of these pSNPs among features such as conserved regions, repeats, and dinucleotides as well as Gene Ontology terms. This report supports the functional relevance of several of the pSNPs investigated and suggests a putative impact on disease susceptibility.
authors.affiliation: Division of Hematology-Oncology, Research Center, Sainte-Justine Hospital, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, Canada QC H3T 1C5. daniel.sinnett@umontreal.ca
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
authors.forename: Patrick
authors.initials: P
authors.lastname: Beaulieu
authors.forename: Hélène
authors.initials: H
authors.lastname: Bélanger
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lefebvre
authors.forename: Sylvie
authors.initials: S
authors.lastname: Langlois
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Théberge
authors.forename: Simon
authors.initials: S
authors.lastname: Drouin
authors.forename: Corinne
authors.initials: C
authors.lastname: Zotti
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Damian
authors.initials: D
authors.lastname: Labuda
mesh_terms: D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D004247:DNA