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Article

Genetic Variation in Complex Traits in Transgenic α-Synuclein Strains of Caenorhabditis elegans

1
Laboratory of Nematology, Wageningen University & Reseach, Droevendaalsesteeg 1, 6708PB Wageningen, NL, The Netherlands
2
Biomolecular Research Group, Canterbury Christ Church University, North Holmes Road, Canterbury CT1 1QU, UK
*
Author to whom correspondence should be addressed.
Genes 2020, 11(7), 778; https://doi.org/10.3390/genes11070778
Received: 22 June 2020 / Revised: 7 July 2020 / Accepted: 8 July 2020 / Published: 11 July 2020
(This article belongs to the Special Issue Complex Genetic Loci, 2nd Edition)
Different 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. View Full-Text
Keywords: genetic background; α-synuclein; protein accumulation; C. elegans genetic background; α-synuclein; protein accumulation; C. elegans
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MDPI and ACS Style

Wang, Y.A.; van Sluijs, L.; Nie, Y.; Sterken, M.G.; Harvey, S.C.; Kammenga, J.E. Genetic Variation in Complex Traits in Transgenic α-Synuclein Strains of Caenorhabditis elegans. Genes 2020, 11, 778. https://doi.org/10.3390/genes11070778

AMA Style

Wang YA, van Sluijs L, Nie Y, Sterken MG, Harvey SC, Kammenga JE. Genetic Variation in Complex Traits in Transgenic α-Synuclein Strains of Caenorhabditis elegans. Genes. 2020; 11(7):778. https://doi.org/10.3390/genes11070778

Chicago/Turabian Style

Wang, Yiru A., Lisa van Sluijs, Yu Nie, Mark G. Sterken, Simon C. Harvey, and Jan E. Kammenga 2020. "Genetic Variation in Complex Traits in Transgenic α-Synuclein Strains of Caenorhabditis elegans" Genes 11, no. 7: 778. https://doi.org/10.3390/genes11070778

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