Prioritization of epilepsy associated candidate genes by convergent analysis.
Prioritization of epilepsy associated candidate genes by convergent analysis.
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DOI：
10.1371/journal.pone.0017162
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发表时间：
2011-02-24
期刊：
影响因子：
3.7
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Jia P;Ewers JM;Zhao Z
癫痫是一种影响大量个体的严重神经系统疾病，但癫痫的潜在遗传风险因素仍不清楚。最近的研究揭示了几种复发性拷贝数变异（CNVs）更可能与癫痫相关。这些区域内的负责基因尚未明确与疾病有关，并且它们相互作用的影响尚未完全了解。这些基因的鉴定可能有助于更好地了解癫痫的病理，并为进一步研究提供新的治疗靶点。在这项研究中，我们研究了在最近的一项大规模研究中发现的杂合缺失区域内的基因，包括各种癫痫综合征。通过整合额外的蛋白质-蛋白质相互作用数据，我们构建了这些CNV区域基因的子网络，以及先前研究癫痫的基因。我们观察到两个网络共有的20个基因，主要集中在由GABA受体、BDNF/MAPK信号传导和雌激素受体基因组成的小分子网络中。在最初网络中的数百个基因中，这些基因被趋同的证据指定为可能与癫痫相关。重要的是，发现鉴定的分子网络包含复杂的相互关系，为癫痫的潜在病理学提供了进一步的见解。我们进一步进行了途径富集和串扰分析，并揭示了一个功能图，表明密切相关的神经，免疫和激酶调节途径的显着富集。我们在这里提出的收敛框架提供了一个独特的和强大的方法来筛选和识别有前途的疾病基因的疾病相关的CNV区域中的通常数百至数千个基因。我们的网络和通路分析为癫痫的潜在分子机制提供了重要的启示。该策略可应用于其他复杂疾病的研究。
Epilepsy is a severe neurological disorder affecting a large number of individuals, yet the underlying genetic risk factors for epilepsy remain unclear. Recent studies have revealed several recurrent copy number variations (CNVs) that are more likely to be associated with epilepsy. The responsible gene(s) within these regions have yet to be definitively linked to the disorder, and the implications of their interactions are not fully understood. Identification of these genes may contribute to a better pathological understanding of epilepsy, and serve to implicate novel therapeutic targets for further research. In this study, we examined genes within heterozygous deletion regions identified in a recent large-scale study, encompassing a diverse spectrum of epileptic syndromes. By integrating additional protein-protein interaction data, we constructed subnetworks for these CNV-region genes and also those previously studied for epilepsy. We observed 20 genes common to both networks, primarily concentrated within a small molecular network populated by GABA receptor, BDNF/MAPK signaling, and estrogen receptor genes. From among the hundreds of genes in the initial networks, these were designated by convergent evidence for their likely association with epilepsy. Importantly, the identified molecular network was found to contain complex interrelationships, providing further insight into epilepsy's underlying pathology. We further performed pathway enrichment and crosstalk analysis and revealed a functional map which indicates the significant enrichment of closely related neurological, immune, and kinase regulatory pathways. The convergent framework we proposed here provides a unique and powerful approach to screening and identifying promising disease genes out of typically hundreds to thousands of genes in disease-related CNV-regions. Our network and pathway analysis provides important implications for the underlying molecular mechanisms for epilepsy. The strategy can be applied for the study of other complex diseases.
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影响因子：
4
作者：
Miller DT;Shen Y;Weiss LA;Korn J;Anselm I;Bridgemohan C;Cox GF;Dickinson H;Gentile J;Harris DJ;Hegde V;Hundley R;Khwaja O;Kothare S;Luedke C;Nasir R;Poduri A;Prasad K;Raffalli P;Reinhard A;Smith SE;Sobeih MM;Soul JS;Stoler J;Takeoka M;Tan WH;Thakuria J;Wolff R;Yusupov R;Gusella JF;Daly MJ;Wu BL
通讯作者：
Wu BL
影响因子：
30.8
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Helbig I;Mefford HC;Sharp AJ;Guipponi M;Fichera M;Franke A;Muhle H;de Kovel C;Baker C;von Spiczak S;Kron KL;Steinich I;Kleefuss-Lie AA;Leu C;Gaus V;Schmitz B;Klein KM;Reif PS;Rosenow F;Weber Y;Lerche H;Zimprich F;Urak L;Fuchs K;Feucht M;Genton P;Thomas P;Visscher F;de Haan GJ;Møller RS;Hjalgrim H;Luciano D;Wittig M;Nothnagel M;Elger CE;Nürnberg P;Romano C;Malafosse A;Koeleman BP;Lindhout D;Stephani U;Schreiber S;Eichler EE;Sander T
通讯作者：
Sander T
影响因子：
3
作者：
Isojarvi, Jouko
通讯作者：
Isojarvi, Jouko
影响因子：
3.6
作者：
Colmers, William F.;El Bahh, Bouchaib
通讯作者：
El Bahh, Bouchaib
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