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

DSpace/Manakin Repository

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

Citable link to this page

 

 
Title: Large-scale polymorphism discovery in macaque G-protein coupled receptors
Author: Goswami, Dharmendra B; Ogawa, Lisa M; Ward, Joshua M; Miller, Gregory M; Vallender, Eric J

Note: Order does not necessarily reflect citation order of authors.

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.
Full Text & Related Files:
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.
Published Version: doi:10.1186/1471-2164-14-703
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907043/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879677
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters