Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i>
Parkinson’s disease (PD) is a heterogeneous and complex neurodegenerative disorder and large-scale genetic studies have identified >130 genes associated with PD. Although genomic studies have been decisive for our understanding of the genetic contributions underlying PD, these associations remain...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Insects |
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| Online Access: | https://www.mdpi.com/2075-4450/14/2/168 |
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| author | Amalie Elton Baisgaard Kristina Magaard Koldby Torsten Nygård Kristensen Mette Nyegaard Palle Duun Rohde |
| author_facet | Amalie Elton Baisgaard Kristina Magaard Koldby Torsten Nygård Kristensen Mette Nyegaard Palle Duun Rohde |
| author_sort | Amalie Elton Baisgaard |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a heterogeneous and complex neurodegenerative disorder and large-scale genetic studies have identified >130 genes associated with PD. Although genomic studies have been decisive for our understanding of the genetic contributions underlying PD, these associations remain as statistical associations. Lack of functional validation limits the biological interpretation; however, it is labour extensive, expensive, and time consuming. Therefore, the ideal biological system for functionally validating genetic findings must be simple. The study aim was to assess systematically evolutionary conserved PD-associated genes using <i>Drosophila melanogaster</i>. From a literature review, a total of 136 genes have found to be associated with PD in GWAS studies, of which 11 are strongly evolutionary conserved between <i>Homo sapiens</i> and <i>D. melanogaster</i>. By ubiquitous gene expression knockdown of the PD-genes in <i>D. melanogaster</i>, the flies’ escape response was investigated by assessing their negative geotaxis response, a phenotype that has previously been used to investigate PD in <i>D. melanogaster</i>. Gene expression knockdown was successful in 9/11 lines, and phenotypic consequences were observed in 8/9 lines. The results provide evidence that genetically modifying expression levels of PD genes in <i>D. melanogaster</i> caused reduced climbing ability of the flies, potentially supporting their role in dysfunctional locomotion, a hallmark of PD. |
| first_indexed | 2024-03-11T08:39:17Z |
| format | Article |
| id | doaj.art-02cb2ae3577748a39cb0e4c9873c020a |
| institution | Directory Open Access Journal |
| issn | 2075-4450 |
| language | English |
| last_indexed | 2024-03-11T08:39:17Z |
| publishDate | 2023-02-01 |
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| series | Insects |
| spelling | doaj.art-02cb2ae3577748a39cb0e4c9873c020a2023-11-16T21:14:46ZengMDPI AGInsects2075-44502023-02-0114216810.3390/insects14020168Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i>Amalie Elton Baisgaard0Kristina Magaard Koldby1Torsten Nygård Kristensen2Mette Nyegaard3Palle Duun Rohde4Department of Biomedicine, Aarhus University, 8000 Aarhus C, DenmarkDepartment of Health Science and Technology, Aalborg University, 9220 Aalborg, DenmarkDepartment of Chemistry and Bioscience, Aalborg University, 9220 Aalborg, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus C, DenmarkDepartment of Health Science and Technology, Aalborg University, 9220 Aalborg, DenmarkParkinson’s disease (PD) is a heterogeneous and complex neurodegenerative disorder and large-scale genetic studies have identified >130 genes associated with PD. Although genomic studies have been decisive for our understanding of the genetic contributions underlying PD, these associations remain as statistical associations. Lack of functional validation limits the biological interpretation; however, it is labour extensive, expensive, and time consuming. Therefore, the ideal biological system for functionally validating genetic findings must be simple. The study aim was to assess systematically evolutionary conserved PD-associated genes using <i>Drosophila melanogaster</i>. From a literature review, a total of 136 genes have found to be associated with PD in GWAS studies, of which 11 are strongly evolutionary conserved between <i>Homo sapiens</i> and <i>D. melanogaster</i>. By ubiquitous gene expression knockdown of the PD-genes in <i>D. melanogaster</i>, the flies’ escape response was investigated by assessing their negative geotaxis response, a phenotype that has previously been used to investigate PD in <i>D. melanogaster</i>. Gene expression knockdown was successful in 9/11 lines, and phenotypic consequences were observed in 8/9 lines. The results provide evidence that genetically modifying expression levels of PD genes in <i>D. melanogaster</i> caused reduced climbing ability of the flies, potentially supporting their role in dysfunctional locomotion, a hallmark of PD.https://www.mdpi.com/2075-4450/14/2/168model organismneurodegenerative diseaseRING assayclimbing ability |
| spellingShingle | Amalie Elton Baisgaard Kristina Magaard Koldby Torsten Nygård Kristensen Mette Nyegaard Palle Duun Rohde Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i> Insects model organism neurodegenerative disease RING assay climbing ability |
| title | Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i> |
| title_full | Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i> |
| title_fullStr | Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i> |
| title_full_unstemmed | Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i> |
| title_short | Functionally Validating Evolutionary Conserved Risk Genes for Parkinson’s Disease in <i>Drosophila melanogaster</i> |
| title_sort | functionally validating evolutionary conserved risk genes for parkinson s disease in i drosophila melanogaster i |
| topic | model organism neurodegenerative disease RING assay climbing ability |
| url | https://www.mdpi.com/2075-4450/14/2/168 |
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