Large-scale polymorphism discovery in macaque G-protein coupled receptors

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Large-scale polymorphism discovery in macaque G-protein coupled receptors

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dc.contributor.author Goswami, Dharmendra B en_US
dc.contributor.author Ogawa, Lisa M en_US
dc.contributor.author Ward, Joshua M en_US
dc.contributor.author Miller, Gregory M en_US
dc.contributor.author Vallender, Eric J en_US
dc.date.accessioned 2014-03-11T13:27:33Z
dc.date.issued 2013 en_US
dc.identifier.citation Goswami, Dharmendra B, Lisa M Ogawa, Joshua M Ward, Gregory M Miller, and Eric J Vallender. 2013. “Large-scale polymorphism discovery in macaque G-protein coupled receptors.” BMC Genomics 14 (1): 703. doi:10.1186/1471-2164-14-703. http://dx.doi.org/10.1186/1471-2164-14-703. en
dc.identifier.issn 1471-2164 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879677
dc.description.abstract Background: G-protein coupled receptors (GPCRs) play an inordinately large role in human health. Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. Recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes. This work aims to extend those studies broadly across the roughly 377 non-olfactory GPCRs. Initial efforts include resequencing 44 Indian-origin rhesus macaques (Macaca mulatta), 20 Chinese-origin rhesus macaques, and 32 cynomolgus macaques (M. fascicularis). Results: Using the Agilent target enrichment system, capture baits were designed for GPCRs off the human and rhesus exonic sequence. Using next generation sequencing technologies, nearly 25,000 SNPs were identified in coding sequences including over 14,000 non-synonymous and more than 9,500 synonymous protein-coding SNPs. As expected, regions showing the least evolutionary constraint show greater rates of polymorphism and greater numbers of higher frequency polymorphisms. While the vast majority of these SNPs are singletons, roughly 1,750 non-synonymous and 2,900 synonymous SNPs were found in multiple individuals. Conclusions: In all three populations, polymorphism and divergence is highly concentrated in N-terminal and C-terminal domains and the third intracellular loop region of GPCRs, regions critical to ligand-binding and signaling. SNP frequencies in macaques follow a similar pattern of divergence from humans and new polymorphisms in primates have been identified that may parallel those seen in humans, helping to establish better non-human primate models of disease. en
dc.language.iso en_US en
dc.publisher BioMed Central en
dc.relation.isversionof doi:10.1186/1471-2164-14-703 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907043/pdf/ en
dash.license LAA en_US
dc.subject Resequencing en
dc.subject Single-nucleotide polymorphism en
dc.subject Indian-origin rhesus macaques en
dc.subject Chinese-origin rhesus macaques en
dc.subject Cynomolgus macaques en
dc.title Large-scale polymorphism discovery in macaque G-protein coupled receptors en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal BMC Genomics en
dash.depositing.author Goswami, Dharmendra B en_US
dc.date.available 2014-03-11T13:27:33Z

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