Cis-acting regulation of brain-specific ANK3 gene expression by a genetic variant associated with bipolar disorder.
Cis-acting regulation of brain-specific ANK3 gene expression by a genetic variant associated with bipolar disorder.
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DOI：
10.1038/mp.2012.104
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发表时间：
2013-08
影响因子：
11
通讯作者：
Sklar, P.
中科院分区：
文献类型：
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作者：
Rueckert, E. H.;Barker, D.;Ruderfer, D.;Bergen, S. E.;O'Dushlaine, C.;Luce, C. J.;Sheridan, S. D.;Theriault, K. M.;Chambert, K.;Moran, J.;Purcell, S. M.;Madison, J. M.;Haggarty, S. J.;Sklar, P.
多项针对双相情感障碍(BD)的全基因组关联研究发现Ankyrin3(ANK3)基因具有很强的相关性。这种关联跨越了与ANK3重叠的~250kb基因组区域中的大量连锁单核苷酸多态(SNPs)。相关区域包含预测的调控元件以及六个已验证的备选第一外显子中的两个，这些外显子编码蛋白质N-末端的不同蛋白质结构域，也称为AnkG(ankyrin-G)。利用RNA连接酶介导的cDNA末端快速扩增(RLM-RACE)结合高灵敏度、外显子特异性的多重mRNA表达分析，我们在死后的人脑和人干细胞来源的神经前体和神经元中检测到不同的ANK3转录起始点(TSS)的差异调控以及特定的5‘末端与3’mRNA剪接事件的耦合。此外，BD相关SNP rs1938526上的等位基因变异与小脑ANK3转录本表达的显著差异相关。这些发现提示ANK3的脑特异性顺式调控转录效应可能与BD的病理生理学有关。
Several genome-wide association studies (GWAS) for bipolar disorder (BD) have found a strong association of the Ankyrin3 (ANK3) gene. This association spans numerous linked single nucleotide polymorphisms (SNPs) in a ~250 kb genomic region overlapping ANK3. The associated region encompasses predicted regulatory elements as well as two of six validated alternative first exons, which encode distinct protein domains at the N-terminus of the protein also known as ankyrin-G (AnkG). Using RNA Ligase-Mediated Rapid Amplification of cDNA Ends (RLM-RACE) to identify novel transcripts in conjunction with a highly sensitive, exon-specific multiplexed mRNA expression assay, we detected differential regulation of distinct ANK3 transcription start sites (TSSs) and coupling of specific 5’ ends with 3’ mRNA splicing events in post-mortem human brain and human stem cell-derived neural progenitors and neurons. Furthermore, allelic variation at the BD–associated SNP rs1938526 correlated with a significant difference in cerebellar expression of a brain-specific ANK3 transcript. These findings suggest a brain-specific cis-regulatory transcriptional effect of ANK3 may be relevant to BD pathophysiology.
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DOI：
10.1523/jneurosci.4064-11.2011
发表时间：
2011-11-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Grubb MS;Shu Y;Kuba H;Rasband MN;Wimmer VC;Bender KJ
通讯作者：
Bender KJ
影响因子：
3.7
作者：
Hopitzan, AA;Baines, AJ;Kordeli, E
通讯作者：
Kordeli, E
影响因子：
5.4
作者：
Roussos, Panos;Giakoumaki, Stella G.;Bitsios, Panos
通讯作者：
Bitsios, Panos
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
11
作者：
通讯作者：
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