The effect of SNCA 3' region on the levels of SNCA-112 splicing variant.
The effect of SNCA 3' region on the levels of SNCA-112 splicing variant.
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DOI：
10.1007/s10048-010-0263-4
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发表时间：
2011-02
期刊：
影响因子：
2.2
通讯作者：
Chiba-Falek, Ornit
中科院分区：
文献类型：
--
作者：
McCarthy, Jeanette J.;Linnertz, Colton;Saucier, Laura;Burke, James R.;Hulette, Christine M.;Welsh-Bohmer, Kathleen A.;Chiba-Falek, Ornit
SNCA位点3 '区域的遗传变异反复与散发性帕金森病（PD）的易感性相关。越来越多的证据强调SNCA的剂量和表达水平在PD发病机制中的重要性。然而，SNCA基因3 '区调控散发性PD发病风险的机制尚不清楚。我们在117例神经病理正常的人类大脑额叶皮层样本中研究了snca3 '区PD风险相关变异对SNCA112-mRNA（帧内外显子5跳变）水平的影响。标记snca3 '的SNPs对SNCA112-mRNA的相对水平有显著影响。“危险”等位基因与总SNCA112-mRNA表达比例增加相关。我们提供了pd相关的SNCA基因3 '区变异的功能后果的证据，表明SNCA剪接的遗传调控在疾病的发展中起着重要作用。进一步的研究确定snca3 '中明确的功能变异/s，并确定其与PD病理的关系是必要的。
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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影响因子：
11.2
作者：
Scholz, Sonja W.;Houlden, Henry;Schulte, Claudia;Sharma, Manu;Li, Abi;Berg, Daniela;Melchers, Anna;Paudel, Reema;Gibbs, J. Raphael;Simon-Sanchez, Javier;Paisan-Ruiz, Coro;Bras, Jose;Ding, Jinhui;Chen, Honglei;Traynor, Bryan J.;Arepalli, Sampath;Zonozi, Ryan R.;Revesz, Tamas;Holton, Janice;Wood, Nick;Lees, Andrew;Oertel, Wolfgang;Wuellner, Ullrich;Goldwurm, Stefano;Pellecchia, Maria Teresa;Illig, Thomas;Riess, Olaf;Fernandez, Hubert H.;Rodriguez, Ramon L.;Okun, Michael S.;Poewe, Werner;Wenning, Gregor K.;Hardy, John A.;Singleton, Andrew B.;Gasser, Thomas
通讯作者：
Gasser, Thomas
影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
影响因子：
4.4
作者：
CAMPION, D;MARTIN, C;FREBOURG, T
通讯作者：
FREBOURG, T
影响因子：
30.8
作者：
Satake, Wataru;Nakabayashi, Yuko;Toda, Tatsushi
通讯作者：
Toda, Tatsushi
影响因子：
56.9
作者：
Singleton, AB;Farrer, M;Gwinn-Hardy, K
通讯作者：
Gwinn-Hardy, K