Genetic variation in complex traits in transgenic α-synuclein strains of Caenorhabditis elegans

Journal article


Wang, Y., van Sluijs, L., Nie, Y., Sterken, M.G., Harvey, S. and Kammenga, J.E. 2020. Genetic variation in complex traits in transgenic α-synuclein strains of Caenorhabditis elegans. Genes. 11 (7), p. 778.
AuthorsWang, Y., van Sluijs, L., Nie, Y., Sterken, M.G., Harvey, S. and Kammenga, J.E.
Abstract

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.

KeywordsGenetic background; α-synuclein; protein accumulation; C. elegans
Year2020
JournalGenes
Journal citation11 (7), p. 778
PublisherMDPI
ISSN2073-4425
Digital Object Identifier (DOI)doi:10.3390/genes11070778
Official URLhttp://doi.org/10.3390/genes11070778
https://www.mdpi.com/2073-4425/11/7/778
FunderLeverhulme Trust
Publication dates
Print13 Jul 2020
Publication process dates
Accepted08 Jul 2020
Deposited13 Jul 2020
Accepted author manuscript
File Access Level
Restricted
Output statusPublished
Permalink -

https://repository.canterbury.ac.uk/item/8vxy9/genetic-variation-in-complex-traits-in-transgenic-synuclein-strains-of-caenorhabditis-elegans

  • 3
    total views
  • 1
    total downloads
  • 2
    views this month
  • 0
    downloads this month

Export as

Related outputs

Eukaryotic response to hypothermia in relation to integrated stress responses
Adjirackor, N. A., Harvey, K. E. and Harvey, S. C. 2020. Eukaryotic response to hypothermia in relation to integrated stress responses. Cell Stress & Chaperones.
Genetic background modifies phenotypic and transcriptional responses in a C. elegans model of α-synuclein toxicity
Wang, Y., Snoek, B., Sterken, M., Riksen, J., Stastna, J., Kammenga, J. and Harvey, S. 2019. Genetic background modifies phenotypic and transcriptional responses in a C. elegans model of α-synuclein toxicity. BMC Genomics. 20 (1), p. 232.
A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits
Snoek, L., Volkers, R., Petersen, C., Dirksen, P., Sterken, M., Nakad, R., Riksen, J., Ronsenstiel, P., Stastna, J., Braeckman, B., Harvey, S., Schulenburg, H., Kammenga, J. and Nijveen, H. 2019. A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits. BMC Biology.
Cryopreservation produces limited long-term effects on the nematode Caenorhabditis elegans
Stastna, J., Yiapanas, A., Mandawala, D., Fowler, K. and Harvey, S. 2019. Cryopreservation produces limited long-term effects on the nematode Caenorhabditis elegans . Cryobiology .
Synthesis of gold functionalised nanoparticles with the eranthis hyemalis lectin and preliminary toxicological studies on caenorhabditis elegans
Djafari, J., McConnell, M., Santos, H., Capelo, J., Bertolo-Pardo, E., Harvey, S., Lodeiro, C. and Fernández-Lodeiro, J. 2018. Synthesis of gold functionalised nanoparticles with the eranthis hyemalis lectin and preliminary toxicological studies on caenorhabditis elegans. Materials. 11 (8).
The production of pig preimplantation embryos in vitro: current progress and future prospects
Fowler, K., Mandawala, A., Griffin, D., Walling, G. and Harvey, S. 2018. The production of pig preimplantation embryos in vitro: current progress and future prospects. Reproductive Biology. 18 (3), pp. 203-211.
Canine recommended breed weight ranges are not a good predictor of an ideal body condition score
Smith, E., Davis, K., Sulsh, L., Harvey, S., Fowler, K., Canterbury Christ Church University and Portland Road Veterinary Surgery 2018. Canine recommended breed weight ranges are not a good predictor of an ideal body condition score. Journal Of Animal Physiology And Nutrition. 102 (4), pp. 1088-1090.
Mutation independently affects reproductive traits and dauer larvae development in mutation accumulation lines of Caenorhabditis elegans
Hills, A., Green, J. and Harvey, S. 2017. Mutation independently affects reproductive traits and dauer larvae development in mutation accumulation lines of Caenorhabditis elegans. Development genes and evolution. 227 (6), pp. 411-414.
Consensus statement on placebo effects in sports and exercise: the need for conceptual clarity, methodological rigour, and the elucidation of neurobiological mechanisms.
Beedie, C., Hurst, P., Coleman, D., Foad, A., Benedetti, F., Cohen, E., Davis, A., Elseworth-Edelsten, C., Flowers, E., Roelands, B., Hettinga, F., Raglin, J., Szabo, A., Camerone, E., Barbiani, D., Lane, A., Lindheimer, J., Schiphof-Godart, l. and Harvey, S. 2018. Consensus statement on placebo effects in sports and exercise: the need for conceptual clarity, methodological rigour, and the elucidation of neurobiological mechanisms. European Journal of Sport Science.
Studying placebo effects in model organisms will help us understand them in humans
Harvey, S. and Beedie, C. 2017. Studying placebo effects in model organisms will help us understand them in humans. Biology Letters. 13 (11).
Genetic variation in neurodegenerative diseases and its accessibility in the model organism Caenorhabditis elegans
Wang, Y., Kammenga, J. and Harvey, S. 2017. Genetic variation in neurodegenerative diseases and its accessibility in the model organism Caenorhabditis elegans. Human Genomics. 11 (1).
Reimagining pheromone signalling in the model nematode Caenorhabditis elegans
Viney, M. and Harvey, S. 2017. Reimagining pheromone signalling in the model nematode Caenorhabditis elegans. PLoS Genetics. 13 (11), p. e1007046.
Time-lapse embryo imaging and morphokinetic profiling: towards a general characterisation of embryogenesis
Mandawala, A., Harvey, S., Roy, T. and Fowler, K. 2016. Time-lapse embryo imaging and morphokinetic profiling: towards a general characterisation of embryogenesis. Animal Reproduction Science. 174, pp. 2-10.
Cryopreservation of animal oocytes and embryos: current progress and future prospects
Mandawala, A., Harvey, S., Roy, T. and Fowler, K. 2016. Cryopreservation of animal oocytes and embryos: current progress and future prospects. Theriogenology. 86 (7), pp. 1637-1644.
Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option
Gilabert, A., Curran, D., Harvey, S. and Wasmuth, J. 2016. Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option. BMC Genomics. 17, p. 476.
Winter Aconite (Eranthis hyemalis) Lectin as a cytotoxic effector in the lifecycle of Caenorhabditis elegans
McConnell, M., Lisgarten, D., Byrne, L., Harvey, S. and Bertolo-Pardo, E. 2015. Winter Aconite (Eranthis hyemalis) Lectin as a cytotoxic effector in the lifecycle of Caenorhabditis elegans. PeerJ.
Genotype-dependent lifespan effects in peptone deprived Caenorhabditis elegans
Stastna, J., Snoek, L., Kammenga, J. and Harvey, S. 2015. Genotype-dependent lifespan effects in peptone deprived Caenorhabditis elegans. Scientific Reports. 5 (16259).
Widespread genomic incompatibilities in Caenorhabditis elegans
Snoek, L., Orbidans, H., Stastna, J., Aartse, A., Rodriguez, M., Riksen, J., Kammenga, J. and Harvey, S. 2014. Widespread genomic incompatibilities in Caenorhabditis elegans. G3. 4 (10), pp. 1813-1823.
Highly polygenic variation in environmental perception determines dauer larvae formation in growing populations of Caenorhabditis elegans
Green, J., Stastna, J., Orbidans, H. and Harvey, S. 2014. Highly polygenic variation in environmental perception determines dauer larvae formation in growing populations of Caenorhabditis elegans. PLoS ONE. 9 (11), p. e112830.
Genetic mapping of variation in dauer larvae development in growing populations of Caenorhabditis elegans
Green, J., Snoek, L., Kammenga, J. and Harvey, S. 2013. Genetic mapping of variation in dauer larvae development in growing populations of Caenorhabditis elegans. Heredity.
Caenorhabditis elegans dauer larvae development in growing populations.
Green, J. and Harvey, S. 2012. Caenorhabditis elegans dauer larvae development in growing populations. Nematology. 14 (2), pp. 165-173.
A distributed systems approach to undergraduate assessment
Bertolo-Pardo, E. and Harvey, S. 2011. A distributed systems approach to undergraduate assessment.
Enhancing the teaching-research nexus in the undergraduate curriculum through assessment
Bertolo-Pardo, E., Capelo, J., Harvey, S. and Lodeiro, C. 2012. Enhancing the teaching-research nexus in the undergraduate curriculum through assessment.
All eggs are not equal: the maternal environment affects progeny reproduction and developmental fate in Caenorhabditis elegans
Harvey, S. and Orbidans, H. 2011. All eggs are not equal: the maternal environment affects progeny reproduction and developmental fate in Caenorhabditis elegans. PLoS ONE. 6 (10), p. e25840.
Thermal stress responses in Caenorhabditis elegans: reproductive effects, natural variation and the costs of hormesis
Harvey, S. 2010. Thermal stress responses in Caenorhabditis elegans: reproductive effects, natural variation and the costs of hormesis.
Population growth and dauer larva development in Caenorhabditis elegans
Green, J. and Harvey, S. 2010. Population growth and dauer larva development in Caenorhabditis elegans.
Towards modelling the ecology of Caernorhabditis elegans: dauer larvae development in growing populations
Green, J. and Harvey, S. 2011. Towards modelling the ecology of Caernorhabditis elegans: dauer larvae development in growing populations.
Quantitative genetic analysis of life-history traits of Caenorhabditis elegans in stressful environments
Harvey, S., Shorto, A. and Viney, M. 2008. Quantitative genetic analysis of life-history traits of Caenorhabditis elegans in stressful environments. BMC Evolutionary Biology. 8 (1), p. 15.
Heterogeneity in the distribution of Strongyloides ratti infective stages among the faecal pellets of rats
Harvey, S., Paterson, S. and Viney, M. 1999. Heterogeneity in the distribution of Strongyloides ratti infective stages among the faecal pellets of rats. Parasitology. 119 (2), pp. 227-235.
The control of morph development in the parasitic nematode Strongyloides ratti
Harvey, S., Gemmill, A., Read, A. and Viney, M. 2000. The control of morph development in the parasitic nematode Strongyloides ratti. Proceedings of the Royal Society B: Biological Sciences. 267 (1457), pp. 2057-2063.
Sex determination in the parasitic nematode Strongyloides ratti
Harvey, S. and Viney, M. 2001. Sex determination in the parasitic nematode Strongyloides ratti. Genetics. 158, pp. 1527-1533.
Identification of putative sex chromosomes in the blue tilapia, Oreochromis aureus, through synaptonemal complex and FISH analysis
Campos-Ramos, R., Harvey, S., Masabanda, J., Carrasco, L., Griffin, D., McAndrew, B., Bromage, N. and Penman, D. 2001. Identification of putative sex chromosomes in the blue tilapia, Oreochromis aureus, through synaptonemal complex and FISH analysis. Genetica. 111 (1/3), pp. 143-153.
Karyotype analysis of Oreochromis mortimeri (Trewavas) and Sarotherodon melanotheron (Ruppell)
Harvey, S., Powell, S., Kennedy, D., McAndrew, B. and Penman, D. 2002. Karyotype analysis of Oreochromis mortimeri (Trewavas) and Sarotherodon melanotheron (Ruppell). Aquaculture Research. 33 (5), pp. 339-342.
Molecular-cytogenetic analysis reveals sequence differences between the sex chromosomes of Oreochromis niloticus: evidence for an early stage of sex-chromosome differentiation
Harvey, S., Masabanda, J., Carrasco, L., Bromage, N., Penman, D. and Griffin, D. 2002. Molecular-cytogenetic analysis reveals sequence differences between the sex chromosomes of Oreochromis niloticus: evidence for an early stage of sex-chromosome differentiation. Cytogenetic and Genome Research. 97 (1-2), pp. 76-80.
Karyotype evolution in tilapia: mitotic and meiotic chromosome analysis of Oreochromis Karongae and O. Niloticus × O. Karongae hybrids
Harvey, S., Campos-Ramos, R., Kennedy, D., Ezaz, M., Bromage, N., Griffin, D. and Penman, D. 2002. Karyotype evolution in tilapia: mitotic and meiotic chromosome analysis of Oreochromis Karongae and O. Niloticus × O. Karongae hybrids. Genetica. 115 (2), pp. 169-177.
Early origins of the X and Y chromosomes: lessons from tilapia
Griffin, D., Harvey, S., Campos-Ramos, R., Ayling, L., Bromage, N., Masabanda, J. and Penman, D. 2002. Early origins of the X and Y chromosomes: lessons from tilapia. Cytogenetic and Genome Research. 99 (1-4), pp. 157-163.
An investigation of sex determination in the Mozambique tilapia, Oreochromis mossambicus, using synaptonemal complex analysis, FISH, sex reversal and gynogenesis
Campos-Ramos, R., Harvey, S., McAndrew, B. and Penman, D. 2003. An investigation of sex determination in the Mozambique tilapia, Oreochromis mossambicus, using synaptonemal complex analysis, FISH, sex reversal and gynogenesis. Aquaculture. 221 (1-4), pp. 125-140.
Physical mapping of the brain and ovarian aromatase genes in the Nile tilapia, Oreochromis niloticus, by fluorescence in situ hybridization
Harvey, S., Kwon, J. and Penman, D. 2003. Physical mapping of the brain and ovarian aromatase genes in the Nile tilapia, Oreochromis niloticus, by fluorescence in situ hybridization. Animal Genetics. 34 (1), pp. 62-64.
Analysis of repetitive DNA sequences in the sex chromosomes of Oreochromis niloticus
Harvey, S., Boonphakdee, C., Campos-Ramos, R., Ezaz, M., Griffin, D., Bromage, N. and Penman, D. 2003. Analysis of repetitive DNA sequences in the sex chromosomes of Oreochromis niloticus. Cytogenetic and Genome Research. 101 (3-4), pp. 314-319.
Isolation and physical mapping of sex-linked AFLP markers in Nile tilapia (Oreochromis niloticus L.)
Ezaz, M., Harvey, S., Boonphakdee, C., Teale, A., McAndrew, B. and Penman, D. 2004. Isolation and physical mapping of sex-linked AFLP markers in Nile tilapia (Oreochromis niloticus L.). Marine Biotechnology. 6 (5), pp. 435-445.
Thermal variation reveals natural variation between isolates of Caenorhabditis elegans
Harvey, S. and Viney, M. 2007. Thermal variation reveals natural variation between isolates of Caenorhabditis elegans. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. 308B (4), pp. 409-416.
Sex-specific differences in the synaptonemal complex in the genus Oreochromis (Cichlidae)
Campos-Ramos, R., Harvey, S. and Penman, D. 2009. Sex-specific differences in the synaptonemal complex in the genus Oreochromis (Cichlidae). Genetica. 135 (3), pp. 325-332.
Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans
Harvey, S., Barker, G., Shorto, A. and Viney, M. 2009. Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans. BMC Genomics. 10 (1), p. 325.
Non-dauer larval dispersal in Caenorhabditis elegans
Harvey, S. 2009. Non-dauer larval dispersal in Caenorhabditis elegans. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution. 312B (3), pp. 224-230.