Structural variants in SNCA gene and the implication to synucleinopathies.
Structural variants in SNCA gene and the implication to synucleinopathies.
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DOI：
10.1016/j.gde.2017.01.014
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发表时间：
2017-06
影响因子：
4
通讯作者：
Chiba-Falek O
中科院分区：
文献类型：
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作者：
Chiba-Falek O
突触核蛋白病是一组神经退行性疾病，其共同的病理病变是细胞内蛋白包涵体，主要由 α-突触核蛋白聚集体组成。包括全基因组关联研究在内的越来越多的证据表明，α-突触核蛋白 (SNCA) 基因与突触核蛋白病的病因有关，并且有人认为 SNCA 表达水平对于这些疾病的发生至关重要。本综述重点关注结构变异 (SV) 类别的遗传变异，包括 SNCA 位点内大基因组片段和短 (<50bp) 基因组变异（例如简单序列重复 (SSR)）的倍增。我们提供的证据表明，SNCA-SV 通过影响基因表达以及转录和剪接等调控机制，在突触核蛋白病的发病机制中发挥着关键作用。
Synucleinopathies are a group of neurodegenerative diseases that share a common pathological lesion of intracellular protein inclusions largely composed of aggregates of alpha-synuclein protein. Accumulating evidence, including genome-wide association studies, has implicated the alpha-synuclein (SNCA) gene in the etiology of synucleinopathies and it has been suggested that SNCA expression levels are critical for the development of these diseases. This review focuses on genetic variants from the class of structural variants (SVs), including multiplication of large genomic segments and short (<50bp) genomic variants such as simple sequence repeats (SSRs), within the SNCA locus. We provide evidence that SNCA-SVs play a key role in the pathogenesis of synucleinopathies via their effects on gene expression and on regulatory mechanisms including transcription and splicing.