Chiba-Falek Ornit
Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA; Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA.
Curr Opin Genet Dev. 2017 Jun;44:110-116. doi: 10.1016/j.gde.2017.01.014. Epub 2017 Mar 2.
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.
突触核蛋白病是一组神经退行性疾病，它们具有共同的病理病变，即细胞内蛋白质包涵体，主要由α-突触核蛋白聚集体组成。越来越多的证据，包括全基因组关联研究，表明α-突触核蛋白（SNCA）基因与突触核蛋白病的病因有关，并且有人提出SNCA表达水平对这些疾病的发展至关重要。本综述聚焦于SNCA基因座内结构变异（SVs）类别的遗传变异，包括大基因组片段的倍增以及短（<50bp）基因组变异，如简单序列重复（SSRs）。我们提供的证据表明，SNCA-SVs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起关键作用。
