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dc.contributor.authorGoswami, Dharmendra Ben_US
dc.contributor.authorOgawa, Lisa Men_US
dc.contributor.authorWard, Joshua Men_US
dc.contributor.authorMiller, Gregory Men_US
dc.contributor.authorVallender, Eric Jen_US
dc.date.accessioned2014-03-11T13:27:33Z
dc.date.issued2013en_US
dc.identifier.citationGoswami, 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.issn1471-2164en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879677
dc.description.abstractBackground: 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.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1471-2164-14-703en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907043/pdf/en
dash.licenseLAAen_US
dc.subjectResequencingen
dc.subjectSingle-nucleotide polymorphismen
dc.subjectIndian-origin rhesus macaquesen
dc.subjectChinese-origin rhesus macaquesen
dc.subjectCynomolgus macaquesen
dc.titleLarge-scale polymorphism discovery in macaque G-protein coupled receptorsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMC Genomicsen
dash.depositing.authorGoswami, Dharmendra Ben_US
dc.date.available2014-03-11T13:27:33Z
dc.identifier.doi10.1186/1471-2164-14-703*
dash.contributor.affiliatedMiller, Gregory Michael
dash.contributor.affiliatedGoswami, Dharmendra B
dash.contributor.affiliatedOgawa, Lisa M
dash.contributor.affiliatedVallender, Eric


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