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Characterizing dopaminergic neuron vulnerability using genome-wide analysis
Parkinson’s disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Dro...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864742/ https://www.ncbi.nlm.nih.gov/pubmed/34038543 http://dx.doi.org/10.1093/genetics/iyab081 |
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author | Davis, Jacinta Da Silva Santos, Claire Zavala, Narda Caudillo Gans, Nicholas Patracuolla, Daniel Fehrenbach, Monica Babcock, Daniel T |
author_facet | Davis, Jacinta Da Silva Santos, Claire Zavala, Narda Caudillo Gans, Nicholas Patracuolla, Daniel Fehrenbach, Monica Babcock, Daniel T |
author_sort | Davis, Jacinta |
collection | PubMed |
description | Parkinson’s disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Drosophila melanogaster as part of the Drosophila Genetic Reference Panel. Here, we identify the top-associated genes containing single-nucleotide polymorphisms that render DA neurons vulnerable. These genes were further analyzed by using mutant analysis and tissue-specific knockdown for functional validation. We found that this loss of DA neurons caused progressive locomotor dysfunction in mutants and gene knockdown analysis. The identification of genes associated with the progressive loss of DA neurons should help to uncover factors that render these neurons vulnerable in PD, and possibly develop strategies to make these neurons more resilient. |
format | Online Article Text |
id | pubmed-8864742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88647422022-02-24 Characterizing dopaminergic neuron vulnerability using genome-wide analysis Davis, Jacinta Da Silva Santos, Claire Zavala, Narda Caudillo Gans, Nicholas Patracuolla, Daniel Fehrenbach, Monica Babcock, Daniel T Genetics Neurogenetics Parkinson’s disease (PD) is primarily characterized by the loss of dopaminergic (DA) neurons in the brain. However, little is known about why DA neurons are selectively vulnerable to PD. To identify genes that are associated with DA neuron loss, we screened through 201 wild-caught populations of Drosophila melanogaster as part of the Drosophila Genetic Reference Panel. Here, we identify the top-associated genes containing single-nucleotide polymorphisms that render DA neurons vulnerable. These genes were further analyzed by using mutant analysis and tissue-specific knockdown for functional validation. We found that this loss of DA neurons caused progressive locomotor dysfunction in mutants and gene knockdown analysis. The identification of genes associated with the progressive loss of DA neurons should help to uncover factors that render these neurons vulnerable in PD, and possibly develop strategies to make these neurons more resilient. Oxford University Press 2021-05-26 /pmc/articles/PMC8864742/ /pubmed/34038543 http://dx.doi.org/10.1093/genetics/iyab081 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Neurogenetics Davis, Jacinta Da Silva Santos, Claire Zavala, Narda Caudillo Gans, Nicholas Patracuolla, Daniel Fehrenbach, Monica Babcock, Daniel T Characterizing dopaminergic neuron vulnerability using genome-wide analysis |
title | Characterizing dopaminergic neuron vulnerability using genome-wide analysis |
title_full | Characterizing dopaminergic neuron vulnerability using genome-wide analysis |
title_fullStr | Characterizing dopaminergic neuron vulnerability using genome-wide analysis |
title_full_unstemmed | Characterizing dopaminergic neuron vulnerability using genome-wide analysis |
title_short | Characterizing dopaminergic neuron vulnerability using genome-wide analysis |
title_sort | characterizing dopaminergic neuron vulnerability using genome-wide analysis |
topic | Neurogenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864742/ https://www.ncbi.nlm.nih.gov/pubmed/34038543 http://dx.doi.org/10.1093/genetics/iyab081 |
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