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dc.contributor.authorWang, Yiru A.
dc.contributor.authorvan Sluijs, Lisa
dc.contributor.authorNie, Yu
dc.contributor.authorSterken, Mark G.
dc.contributor.authorHarvey, Simon C.
dc.contributor.authorKammenga, Jan E.
dc.date.accessioned2020-07-12T23:08:56Z
dc.date.available2020-07-12T23:08:56Z
dc.date.issued2020-07-11
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/307872
dc.description.abstractDifferent genetic backgrounds can modify the effect of mutated genes. Human α-synuclein (SNCA) gene encodes α-synuclein, and its oligomeric complexes accumulate with age and mediate the disruption of cellular homeostasis, resulting in the neuronal death that is characteristic of Parkinson’s Disease. Polymorphic variants modulate this complex pathologic mechanism. Previously, we constructed five transgenic introgression lines of a Caenorhabditis elegans model of α-synuclein using genetic backgrounds that are genetically diverse from the canonical wild-type Bristol N2. A gene expression analysis revealed that the α-synuclein transgene differentially affects genome-wide transcription due to background modifiers. To further investigate how complex traits are affected in these transgenic lines, we measured the α-synuclein transgene expression, the overall accumulation of the fusion protein of α-synuclein and yellow fluorescent protein (YFP), the lysosome-related organelles, and the body size. By using quantitative PCR (qPCR), we demonstrated stable and similar expression levels of the α-synuclein transgene in different genetic backgrounds. Strikingly, we observed that the levels of the a-synuclein:YFP fusion protein vary in different genetic backgrounds by using the COPAS™ biosorter. The quantification of the Nile Red staining assay demonstrates that α-synuclein also affects lysosome-related organelles and body size. Our results show that the same α-synuclein introgression in different C. elegans backgrounds can produces differing effects on complex traits due to background modifiers.
dc.languageen
dc.publisherMDPI
dc.subjectgenetic background
dc.subjectα-synuclein
dc.subjectprotein accumulation
dc.subjectC. elegans
dc.titleGenetic Variation in Complex Traits in Transgenic α-Synuclein Strains of Caenorhabditis elegans
dc.typeArticle
dc.date.updated2020-07-12T23:08:55Z
prism.issueIdentifier7
prism.publicationNameGenes
prism.volume11
dc.identifier.doi10.17863/CAM.54966
dcterms.dateAccepted2020-07-08
rioxxterms.versionofrecord10.3390/genes11070778
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidvan Sluijs, Lisa [0000-0002-4692-0844]
dc.contributor.orcidKammenga, Jan E. [0000-0003-4822-4436]
dc.identifier.eissn2073-4425
pubs.funder-project-idNational Institutes of Health (1R01AA026658–01 to J.E.K.)


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