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 (DGRP). Here we identify the top associated genes containing SNPs 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.

中文翻译：

---

使用全基因组分析表征多巴胺能神经元的脆弱性。

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，关于为什么 DA 神经元选择性地易受 PD 影响，我们知之甚少。为了鉴定与 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 (DGRP) 的一部分。在这里，我们确定了含有使 DA 神经元易受攻击的 SNP 的顶级相关基因。通过使用突变分析和组织特异性敲低来进一步分析这些基因以进行功能验证。我们发现这种 DA 神经元的损失导致突变体和基因敲低分析中进行性运动功能障碍。