Distribution of disease-associated copy number variants across distinct disorders of cognitive development.
Distribution of disease-associated copy number variants across distinct disorders of cognitive development.
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DOI：
10.1016/j.jaac.2013.01.003
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发表时间：
2013-04
影响因子：
13.3
通讯作者：
Morrow EM
中科院分区：
文献类型：
--
作者：
Pescosolido MF;Gamsiz ED;Nagpal S;Morrow EM
本研究的目的是发现不同的DSM疾病在多大程度上共享大的、高度重复的拷贝数变异(CNV)作为易感因素。我们还试图根据与CNV的关联来确定诊断组共有的和/或特定诊断特有的基因机制。对PubMed关于自闭症谱系障碍(ASD)、智力障碍(ID)、精神分裂症和癫痫的820篇文章进行系统审查，发现54个CNV与一种或几种障碍有关。对CNV在不同分组中涉及的基因进行通径分析。大多数CNV是在ID中发现的，其他疾病略有归类，但某些CNV与孤立或成群的疾病有关。根据CNV涉及的基因，ID涵盖了自闭症96.8%、精神分裂症92.8%和癫痫100.0%的基因。通路分析表明，突触突触在ASD、ID和精神分裂症中丰富。在ID(肌动蛋白细胞骨架突起)、精神分裂症(泛素相关突起)和ASD(突触小泡运输和胞吐)中发现了疾病特有的过程。智力障碍可能来自最广泛的遗传途径，这些途径的特定子集似乎与其他障碍或这些障碍的组合有关。很明显，认知发育障碍中具有统计学意义的CNV在与突触相关的生物学过程中高度丰富。也有特定于疾病的过程，可能有助于理解这些疾病的不同表现和病理生理学。
The purpose of the present study is to discover the extent to which distinct DSM disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also seek to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs. Systematic review of 820 PubMed articles on autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia, and epilepsy produced 54 CNVs associated with one or several disorders. Pathway analysis on genes implicated by CNVs in different groupings was conducted. The majority of CNVs were found in ID with the other disorders somewhat subsumed, yet certain CNVs were associated with isolated or groups of disorders. Based on genes implicated by CNVs, ID encompassed 96.8% of genes in ASD, 92.8% of genes in schizophrenia, and 100.0% of genes in epilepsy. Pathway analysis revealed that synapse processes were enriched in ASD, ID, and schizophrenia. Disease-specific processes were identified in ID (actin cytoskeleton processes), schizophrenia (ubiquitin-related processes), and ASD (synaptic vesicle transport and exocytosis). Intellectual disability may arise from the broadest range of genetic pathways, and specific subsets of these pathways appear relevant to other disorders or combinations of these disorders. It is clear that statistically significant CNVs across disorders of cognitive development are highly enriched for biological processes related to the synapse. There are also disorder-specific processes that may aid in understanding the distinct presentations and pathophysiology of these disorders.
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影响因子：
30.8
作者：
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：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
64.8
作者：
Cook, Edwin H., Jr.;Scherer, Stephen W.
通讯作者：
Scherer, Stephen W.
影响因子：
11
作者：
通讯作者：
--
影响因子：
8.8
作者：
Bachmann-Gagescu, Ruxandra;Mefford, Heather C.;Tsuchiya, Karen D.
通讯作者：
Tsuchiya, Karen D.