Murthy Megha N, Veerappa Avinash M, Seshachalam Keshava B, Ramachandra Nallur B
a Genetics and Genomics Lab, Department of Genetics and Genomics , University of Mysore , Mysore , India.
b Department of Neurology , JSS Hospital , Mysore , India.
Neurol Res. 2016 Sep;38(9):775-85. doi: 10.1080/01616412.2016.1204105. Epub 2016 Jul 11.
Parkinson disease (PD) is a neurological disease responsible for a considerable rate of mortality and morbidity in the society. Since the symptoms of the disease appear much later than the actual onset of neuron degeneration, a majority of cases remain undiagnosed until the manifestation of the symptoms.
In order to investigate the existence of such susceptibility in the population, we analyzed Copy Number Variation (CNV) influences on PD genes in 1715 individuals from 12 different populations.
Overall, 16 CNV-PD genes, 3 known to be causal and 13 associated, were found to be significantly enriched. PARK2, was under heavy burden with ~1% of the population containing CNV in the exonic region. The impact of these genes on the genome and disease pathway was analyzed using several genome analysis tools. Protein interaction network of CNV-PD genes revealed a complex interaction of molecules forming a major hub by the α-Synuclein, whose direct interactors, LRRK2, PARK2 and ATP13A2 are under CNV influence.
We hypothesize that CNVs may not be the initiating event in the pathogenesis of PD and remain latent until additional secondary hits are acquired and also propose novel genes that may fall under the PD pathway which contribute in pathogenesis.
帕金森病（PD）是一种在社会中导致相当高死亡率和发病率的神经疾病。由于该疾病的症状在神经元实际变性开始后很久才出现，大多数病例在症状出现之前仍未被诊断出来。
为了研究人群中这种易感性的存在情况，我们分析了来自12个不同人群的1715名个体中拷贝数变异（CNV）对PD基因的影响。
总体而言，发现16个CNV-PD基因显著富集，其中3个已知为致病基因，13个为相关基因。PARK2负担沉重，约1%的人群在外显子区域存在CNV。使用多种基因组分析工具分析了这些基因对基因组和疾病通路的影响。CNV-PD基因的蛋白质相互作用网络揭示了分子之间的复杂相互作用，α-突触核蛋白形成了一个主要枢纽，其直接相互作用分子LRRK2、PARK2和ATP13A2受到CNV的影响。
我们推测CNV可能不是PD发病机制中的起始事件，而是在获得额外的二次打击之前保持潜伏状态，并且还提出了可能属于PD通路且在发病机制中起作用的新基因。
