生物
外显子
选择性拼接
遗传学
发病机制
RNA剪接
人类遗传学
等位基因
单核苷酸多态性
基因座(遗传学)
基因
基因型
免疫学
核糖核酸
作者
Jeanette McCarthy,Colton Linnertz,Laura Saucier,James R. Burke,Christine M. Hulette,Kathleen A. Welsh‐Bohmer,Ornit Chiba‐Falek
出处
期刊:Neurogenetics
[Springer Nature]
日期:2010-11-03
卷期号:12 (1): 59-64
被引量:56
标识
DOI:10.1007/s10048-010-0263-4
摘要
Genetic variability at the 3' region of SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson's disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However, the mechanism through which the 3' region of SNCA gene modulates the risk to develop sporadic PD remained elusive. We studied the effect of PD risk-associated variants at SNCA 3' regions on SNCA112-mRNA (exon 5 in-frame skipping) levels in vivo in 117 neuropathologically normal, human brain frontal cortex samples. SNPs tagging the SNCA 3' showed significant effects on the relative levels of SNCA112-mRNA from total SNCA transcripts levels. The "risk" alleles were correlated with increased expression ratio of SNCA112-mRNA from total. We provide evidence for functional consequences of PD-associated SNCA gene variants at the 3' region, suggesting that genetic regulation of SNCA splicing plays an important role in the development of the disease. Further studies to determine the definite functional variant/s within SNCA 3'and to establish their association with PD pathology are necessary.
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