Distribution analysis of nonsynonymous polymorphisms within the G-protein-coupled receptor gene family

The G-protein-coupled receptor (GPCR) superfamily is one of the largest classes of proteins in mammalian genomes. GPCRs mediate diverse physiological functions and are the targets of >50% of all clinical drugs. The sequencing of the human genome and large-scale polymorphism discovery efforts have...

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Bibliographic Details
Published in:Genomics (San Diego, Calif.) Calif.), 2003-03, Vol.81 (3), p.245-248
Main Authors: Lee, Andria, Rana, B.K., Schiffer, H.H., Schork, N.J., Brann, M.R., Insel, P.A., Weiner, D.M.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Extracellular loop
Fundamental and applied biological sciences. Psychology
Genes. Genome
GPCR
GTP-Binding Proteins - metabolism
Humans
Molecular and cellular biology
Molecular genetics
Multigene Family
Polymorphism
Polymorphism, Genetic
Protein domain
Receptor
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
SNP
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Summary:The G-protein-coupled receptor (GPCR) superfamily is one of the largest classes of proteins in mammalian genomes. GPCRs mediate diverse physiological functions and are the targets of >50% of all clinical drugs. The sequencing of the human genome and large-scale polymorphism discovery efforts have established an abundant source of single nucleotide polymorphisms (SNPs), particularly those that result in a change in the encoded amino acids (cSNPs), many are of which in GPCRs. Although the majority of these cSNPs are assumed not to be disease-causing (nDCs), experimental data on their functional impact are lacking. Here, we have computationally analyzed the distribution of 454 cSNPs within the GPCR gene family and have found that disease-causing cSNPs (DCs) are overrepresented, whereas nDCs are underrepresented or neutral in transmembrane and extracellular loop domains, respectively. This finding reflects the relative importance of these domains to GPCR function and implies different biological characteristics for the two sets of human polymorphisms.
ISSN:0888-7543
1089-8646
DOI:10.1016/S0888-7543(03)00009-0