Relationships between gene expression and brain wiring in the adult rodent brain.
Relationships between gene expression and brain wiring in the adult rodent brain.
复制标题
DOI：
10.1371/journal.pcbi.1001049
复制
发表时间：
2011-01-06
影响因子：
4.3
通讯作者：
Pavlidis P
中科院分区：
文献类型：
--
作者：
French L;Pavlidis P
我们研究了成年啮齿动物大脑中基因表达与神经解剖连通性之间的全局关系。我们利用来自脑结构管理系统（brain Architecture Management System）的大鼠脑“连接组”数据集（942个脑区域和超过5000个连接），并使用统计方法将数据与来自Allen brain Atlas的142个解剖区域的17530个基因的基因表达特征联系起来。我们的分析表明，成人基因表达特征与连通性有统计学上显著的关系。特别是，具有相似表达谱的大脑区域往往具有相似的连接谱，这种影响并不完全归因于空间相关性。此外，连接的大脑区域有更多相似的表达模式。利用一种简单的优化方法，我们确定了一组与神经解剖学连通性最相关的基因，并发现这组基因丰富，涉及神经元发育和轴突引导。许多基因与神经发育障碍有关，如自闭症谱系障碍。我们的研究结果有可能揭示基因表达模式在影响神经元活动和连通性方面的作用，并有可能应用于我们对大脑疾病的理解。补充数据可从http://www.chibi.ubc.ca/ABAMS获取。我们测试了这样一种观点，即成人大脑的“接线图”与基因表达的位置有关。我们的灵感来自于研究秀丽隐杆线虫的小组所做的类似工作。通过使用啮齿类动物大脑连接和基因表达的大规模数据库，我们发现许多参与大脑发育的基因与解剖连接模式相关。我们发现的一些基因与自闭症等疾病有关，人们怀疑自闭症会影响大脑的连接。虽然我们发现的模式的生物学原因尚不清楚，但我们相信它们为大脑中基因表达的模式提供了新的见解，并将刺激这一问题的进一步研究。
We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS. We tested the idea that the “wiring diagram” of the adult brain has a relationship with where genes are expressed. We were inspired by similar work carried out by groups examining the nematode worm Caenorhabditis elegans. By using large-scale databases of brain connectivity and gene expression in rodents, we found that many genes involved in the development of the brain show correlations with anatomical connectivity patterns. Some of the genes we found have been implicated in disorders such as autism, which is suspected to affect brain wiring. While the biological causes of the patterns we found are not yet known, we believe they provide new insight into the patterns of gene expression in the brain and will spur further study of this problem.
登录
查看更多内容
影响因子：
3.3
作者：
Fuentes-Santamaria, V;Stein, BE;McHaffie, JG
通讯作者：
McHaffie, JG
影响因子：
5.2
作者：
Bonora, E;Lamb, JA;Monaco, AP
通讯作者：
Monaco, AP
影响因子：
4.3
作者：
Baruch, Leehod;Itzkovitz, Shalev;Segal, Eran
通讯作者：
Segal, Eran
影响因子：
3.5
作者：
Bota M;Swanson LW
通讯作者：
Swanson LW
影响因子：
14.9
作者：
Basu SN;Kollu R;Banerjee-Basu S
通讯作者：
Banerjee-Basu S