Characterizing dopaminergic neuron vulnerability using genome-wide analysis.

IF 3.3 3区生物学

Genetics Pub Date : 2021-08-09 DOI:10.1093/genetics/iyab081

Jacinta Davis, Claire Da Silva Santos, Narda Caudillo Zavala, Nicholas Gans, Daniel Patracuolla, Monica Fehrenbach, Daniel T Babcock

引用次数: 5

Abstract

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.

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利用全基因组分析表征多巴胺能神经元易损性。

帕金森病(PD)的主要特征是大脑中多巴胺能(DA)神经元的丧失。然而，对于为什么DA神经元选择性地易受PD的影响，我们知之甚少。为了确定与DA神经元丢失相关的基因，我们筛选了201个野生捕获的黑腹果蝇种群，作为果蝇遗传参考小组的一部分。在这里，我们确定了包含单核苷酸多态性的顶部相关基因，这些基因使DA神经元变得脆弱。通过突变分析和组织特异性敲除进一步分析这些基因的功能验证。我们在突变体和基因敲低分析中发现DA神经元的缺失导致进行性运动功能障碍。鉴定与DA神经元进行性丧失相关的基因，将有助于揭示PD中使这些神经元易损的因素，并可能开发出使这些神经元更具弹性的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics 生物-遗传学

CiteScore

6.20

自引率

6.10%

发文量

177

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.