title: False positive non-synonymous polymorphisms of G-protein coupled receptor genes.
abstract: Polymorphisms of G-protein coupled receptor (GPCR) genes are associated with disease risk and modification, and the response to receptor-directed therapy. Genomic sequencing ( approximately 1700 automated runs) from as many as 120 chromosomes from 60 multiethnic individuals was performed to confirm non-synonymous coding polymorphisms reported in the dbSNP database from 25 randomly selected GPCR genes. These polymorphisms were in regions of the receptors responsible for structural integrity, ligand binding, G-protein coupling and phosphoregulation. However, most of these putative polymorphisms could not be confirmed (false positive rate of 68%). Based on these results, we suggest that the variability of the superfamily is not well defined, and we caution against exclusive reliance on databases for selection of candidate GPCR polymorphisms for disease association and pharmacogenetic studies.
authors.affiliation: Departments of Medicine and Molecular Genetics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Room G062, Cincinnati, OH 45267-0564, USA.
authors.forename: Kersten M
authors.initials: KM
authors.lastname: Small
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Seman
authors.forename: Alex
authors.initials: A
authors.lastname: Castator
authors.forename: Kari M
authors.initials: KM
authors.lastname: Brown
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Liggett
mesh_terms: D030561:Databases, Nucleic Acid; D005189:False Positive Reactions; D019204:GTP-Binding Proteins / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins