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False positive non‐synonymous polymorphisms of G‐protein coupled receptor genes
Author(s) -
Small Kersten M.,
Seman Carrie A.,
Castator Alex,
Brown Kari M.,
Liggett Stephen B.
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02564-4
Subject(s) - genetics , gene , biology
Polymorphisms of G‐protein coupled receptor (GPCR) genes are associated with disease risk and modification, and the response to receptor‐directed therapy. Genomic sequencing (∼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.