Microarray profiling of gene expression in Alpha-Synuclein aggregations and its alteration by natural genetic variation in Caenorhabditis elegans

Yiru A. Wang, L.B. Snoek, M.G. Sterken, J.A.G. Riksen, D. Cook, R.E. Tanny, E.C. Andersen, J.E. Kammenga, S. Harvey

Research output: Contribution to conferencePosterAcademic


Neurodegenerative diseases (NGDs), such as Alzheimer’s diseases (AD) and Parkinson’s diseases (PD), are characterized by progressive degeneration in the human nervous system. The nematode C. elegans is an excellent model in which to study NGDs due to the high level of conservation of gene functions compared to humans. However, C. elegans research largely relies on a single worm genotype – the canonical N2 strain – limiting the ability to explore how naturally varying alleles alter pathological mechanisms in NGDs. In order to identify how genetic variation acts on NGDs, we analyzed transgenic animals that express aggregating human proteins associated with molecular pathogenic progression of NGDs in five genetic backgrounds.

Here, starting with the original transgenic strain expressing the human synaptic protein alpha-synuclein in an N2 genetic background, we have introgressed the PD transgene (unc-54:: α-Syn:: YFP) into four different wild type genetic backgrounds. Analysis of these new transgenic introgressed lines indicates that transgene effects vary greatly depending on the genetic background. To understand the genetic bases of these phenotypic differences, we have sequenced these new lines to recognize confounder of the heterogeneity in transgenes, measured various aspects of the life history, and investigated gene expression differences by microarray. These analyses identified genes that are up- and down-regulated in all genotypes and genes that expressed at a specific stage to particular genetic backgrounds. For example, the differential developments of those lines have been also confirmed from microarray data that the gene vit-1 expressed at different levels between the lines. Functional enrichment links these genes to the aggregation of alpha-synuclein, which is causative of PD, to the associated developmental arrest, metabolic, and cellular repair mechanisms.

Our studies provide opportunities to observe alterations in traits, including global gene expression, associated with the toxicity of misfolded protein aggregation that could not be readily observed in the canonical N2 background. This is a necessary and important step to identify the alleles responsible for individual variation in the onset and progression of NGDs.

Original languageEnglish
Publication statusPublished - 2017
EventThe 21st International C. elegans Meeting 2017 - University of California, Los Angeles, United States
Duration: 21 Jun 201725 Jun 2017


ConferenceThe 21st International C. elegans Meeting 2017
Country/TerritoryUnited States
CityLos Angeles


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