caa a22 4500 445364505 CHVBK 20180317142925.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10048-010-0263-4 doi (NATIONALLICENCE)springer-10.1007/s10048-010-0263-4 The effect of SNCA 3′ region on the levels of SNCA -112 splicing variant [Elektronische Daten] [Jeanette McCarthy, Colton Linnertz, Laura Saucier, James Burke, Christine Hulette, Kathleen Welsh-Bohmer, Ornit Chiba-Falek] 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. Springer-Verlag, 2010 SNCA -mRNA nationallicence SNCA112 nationallicence Splicing nationallicence Parkinson's disease nationallicence Functional variants nationallicence eSNP nationallicence McCarthy Jeanette Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut Linnertz Colton Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut Saucier Laura Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut Burke James Division of Neurology, Department of Medicine, Duke University Medical Center, 27710, Durham, NC, USA aut Hulette Christine Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, 27705, Durham, NC, USA aut Welsh-Bohmer Kathleen Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, 27705, Durham, NC, USA aut Chiba-Falek Ornit Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut neurogenetics Springer-Verlag 12/1(2011-02-01), 59-64 1364-6745 12:1<59 2011 12 10048 https://doi.org/10.1007/s10048-010-0263-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-010-0263-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- McCarthy Jeanette Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Linnertz Colton Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Saucier Laura Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Burke James Division of Neurology, Department of Medicine, Duke University Medical Center, 27710, Durham, NC, USA aut NATIONALLICENCE 700 1- Hulette Christine Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, 27705, Durham, NC, USA aut NATIONALLICENCE 700 1- Welsh-Bohmer Kathleen Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, 27705, Durham, NC, USA aut NATIONALLICENCE 700 1- Chiba-Falek Ornit Institute for Genome Sciences & Policy, Duke University, DUMC, Box3445, 27710, Durham, NC, USA aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/1(2011-02-01), 59-64 1364-6745 12:1<59 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer